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China's-vaccines-are-poised-to-help-less-wealthy-nations,but-face-trust-issues
PUBLISHED FRI, DEC 25 2020 1:28 AM EST
UPDATED FRI, DEC 25 2020 1:28 AM EST
[gew59, Would you take CCP’s vaccine yourself? Don’t be hypocritical. Please give me a definitive answer. No dodging around.]
For those countries that have not yet secured a vaccine, China may be the only solution.
China has six candidates in the last stage of trials and is one of the few nations that can manufacture vaccine on a large scale.
The potential use of its vaccine gives China an opportunity both to repair the damage to its reputation from an outbreak that escaped its borders and to show the world it can be a major scientific player.
Yet past scandals have damaged its own citizens' trust in its vaccines, with manufacturing and supply chain problems casting doubt on whether it can really be a savior.
"A question mark remains over how China can ensure the delivery of reliable vaccines," said Joy Zhang, a professor who studies the ethics of emerging science at the University of Kent in Britain. She cited China's "non-transparency over scientific data and a troubled history with vaccine delivery."
In some countries, Chinese vaccines are viewed with suspicion. Brazil's President Jair Bolsonaro has repeatedly sown doubt about the effectiveness of Chinese company Sinovac's vaccine candidate without citing any evidence, and said Brazilians won't be used as "guinea pigs."
the Wuhan Institute of Biological Products, a Sinopharm subsidiary behind one of the Covid-19 candidates, was caught up in a vaccine scandal in 2018.
Government inspectors found that the company, based in the city where the coronavirus was first detected last year, had made hundreds of thousands of ineffective doses of a combination vaccine for diphtheria, tetanus and whooping cough because of an equipment malfunction.
That same year it was reported that Changsheng Biotechnology Co. falsified data about a rabies vaccine.
In 2016, Chinese media revealed that 2 million doses of various vaccines for children had been improperly stored and sold throughout the country for years.
Vaccination rates fell after those scandals.
"All of my local Chinese friends, they're white-collar, they're well off, and none of them will buy medicine made in China. That's just the way it is," said Ray Yip, former country director of the Gates Foundation in China.
China revised its laws in 2017 and 2019 to tighten management of vaccine storage and step up inspections and penalties for faulty vaccines.
The country's major Covid-19 vaccine developers have published some scientific findings in peer-reviewed scientific journals. But international experts questioned how China recruited volunteers and what kind of tracking there was for possible side effects. Chinese companies and government officials haven't released details.
China revised its laws in 2017 and 2019 to tighten management of vaccine storage and step up inspections and penalties for faulty vaccines.
The country's major Covid-19 vaccine developers have published some scientific findings in peer-reviewed scientific journals. But international experts questioned how China recruited volunteers and what kind of tracking there was for possible side effects. Chinese companies and government officials haven't released details.
Dr Bin Wang of Advaccine is very influential and well-connected in China. I expect 4800 will get EUA in China before in US.
China will likely place gigantic device and Ino-4800 orders, then SK, India, LMICs. The later is through COVAX.
DoD partners with Taiwan in med device, vaccine procurement per Defense Bill NDAA 2021 which I previously posted.
Taiwan may use the same device and vaccine as DoD dictates.
Ino granted Beijing Apollo Saturn Biological Technology Ltd., a license to use the device in Korea starting next year as part of an agreement allegedly valued at more than $30M according to GeneOne's claim.
$16,570,397 firm-fixed-price contract for 900 CELLECTRA 2000 Delivered to DoD by 12/31/20.
$56M CEPI Grant for starting Ino-4700 P2 and Ino-4500 P1 Trials.
Those revenues will show up in 4Q20 10-K.
I expect healthcare names like Phizer,Johnson&Johnson,Novavax,and Inovio Pharma to run higher together into powerful 3rd Waves in 2021
Here's my take on $PFE $JNJ $NVAX and $INO
By PuppyTrades
Inovio Phase I Covid vaccine results 'very promising,' says H.C. Wainwright 06:39 INO H.C. Wainwright analyst Raghuram Selvaraju views the Phase I Covid-19 vaccine results from Inovio Pharmaceuticals last week as "very promising." INO-4800 is stable at room temperature for over a year and at 37 degrees Celsius for over a month, and does not need to be frozen during transportation or storage, which should facilitate global distribution versus mRNA-based COVID-19 vaccines that require cold chain logistics, Selvaraju tells investors in a research note. INO-4800 was immunogenic in 100% of vaccinated subjects with "excellent safety and tolerability," adds the analyst. However, Selvaraju reiterates a Neutral rating on Inovio citing the "nature of the competitive landscape and uncertainty about the future direction of evolution for the pandemic."
Inovio may have viable third-generation vaccine, says Cantor Fitzgerald 07:16 INO Cantor Fitzgerald analyst Charles Duncan keeps a Neutral rating on Inovio Pharmaceuticals with a $15 price target following the company's preliminary report on Phase 1 data for its SARS-CoV-2 vaccine candidate INO-4800. Although potency may not be as great as vaccines from other platforms, over time INO-4800 may prove to be a viable third-generation or booster vaccine for COVID-19, Duncan tells investors in a research note. However, the analyst keeps these prospects in the "show me" category pending additional clinical validation.
12/28/20
Inovio on 'top-10 vaccine contenders list,' says Benchmark 11/17 INO, BNTX, PFE, MRNA Benchmark analyst Aydin Huseynov noted that the reaction in Inovio (INO) shares was "somewhat muted" after the FDA finally cleared the Phase 2 portion of the INO-4800 trial and the company secured full funding for its Phase 2/3 trial from the U.S. Department of Defense, which he attributes to the fact that mRNA vaccine candidates from Pfizer (PFE)-BioNTech (BNTX) and Moderna (MRNA) "set a very high initial bar" for COVID-19 vaccines in development. He said the duration of protection of mRNA vaccines from SARS-CoV2 is yet unknown and "each of the mRNA vaccines has other weak spots," which may lead other governments and ex-US entities to join the consortium for development and financing of INO-4800 once more data is released and confidence grows. Huseynov, who continues to believe that INO-4800 is still "a top-10 vaccine candidate," keeps a Buy rating and $25 price target on Inovio shares.
12/28-31 Possibly 4 PRs next week, 1Q21 Multiple large fundings, and catalysts
1. Delivery of 900 CELLECTRA® 2000 devices
Inovio Pharmaceuticals Inc.,* Plymouth Meeting, Pennsylvania, was awarded a $16,570,397 firm-fixed-price contract for 900 CELLECTRA 2000 DNA vaccine injection devices. Bids were solicited via the internet with one received. Work will be performed in Plymouth Meeting, Pennsylvania, with an estimated completion date of Dec. 31, 2020. Fiscal 2020 defense emergency response funds in the amount of $16,570,397 were obligated at the time of the award. U.S. Army Contracting Command, Aberdeen Proving Ground, Maryland, is the contracting activity (W911QY-20-C-0084). (Awarded June 19, 2020)
2. Advaccine completed P2 enrollment. All 640 participants aged 18-85 received first shot
3. Ino completed P2 enrollment. All 400 participants 18 years older received first shot.
4. 12/23 Completed, Has Result: Study of HPV Specific Immunotherapy in Participants With HPV Associated Head and Neck Squamous Cell Carcinoma
This is a Phase I/IIa, open-label, study to evaluate the safety, tolerability, and immunogenicity of INO-3112 [6 mg of VGX-3100 (2 separate DNA plasmids respectively encoding E6 and E7 proteins of HPV 16 and HPV 18) and 1 mg of INO-9012 (DNA plasmid encoding human interleukin 12)] delivered by electroporation (EP) in up to 25 (twenty-five) participants with HPV positive head and neck cancer. The immunotherapy was studied in the following two groups of participants:
Participants who received immunotherapy before and after definitive surgery (Cohort I)
Participants who received immunotherapy at least 2 months after chemoradiation therapy (Cohort II).
Study: NCT02163057
https://clinicaltrials.gov/ct2/show/NCT02163057?term=NCT02163057&draw=2&rank=1
1Q21 PRs, 10-K:
4800 P2 Wk6 interim result preprint in Lancet
IVI P1 interim result in SK Pre-print.
IVI announces starting P2a. PR first shot.
P3 hold lifted as CELLECTRA® 2000 is used instead of CELLECTRA® 3PSP smart device.
P3 start in March. First shot announced.
$330M DoD funding for P2/3 in 10-K after Defense Bill veto on 12/23 was overridden by Congress last Dec 2020 week.
$384M CEPI funding for
Manufacturing scale-up
COVAX places device and vaccine order.
2nd Ino-4800 shot by Ino in US, Jan
2nd Ino-4800 shot by Advaccine in China, Jan
Ino-4800 will get EUA in China
Before US. Huge device and vaccine orders follow immediately.
REVEAL 1, P3 interim readout. Partnership with upfront payment, milestones payment, and royalty announced.
REVEAL 2, P3 first shot announced
3 separate NHP challenge results by CSIRO, England Public of Health, OWS released
Large second Wave OWS manufacturing scale-up funding awarded to Ino due to stellar P2 result, P3 start, and great duration, efficacy of Ino-4800 from NHP challenge result after OWS gets $20B from new Stimulus package
SII (Serum Institute of India) becomes the largest manufacturing partner.
SK places device and 4800 pre-order
Lassa Fever Ino-4500 first shot announced
MERS P2 Ino-4700 first shot announced
Part of CEPI $56M funding for MERS and Lassa Fever Shows up in 10-K
The release of the peer review for INO-4800 eliminates the FUD (Fear, Uncertainty, and Doubt) that has been the focal point of DNA medicine skeptics and INO short sellers who incorrectly claimed that the vaccine was not able to generate neutralizing antibodies or a positive T-Cell response. They poked fun at the electroporation device and methodology (INOVIO IP = $$) and pointed out Inovio’s lack of manufacturing capacity to even make enough doses of INO-4800 to matter. And yet here we are today with massive manufacturing agreements already in place (Thermo Fisher, Kaneka Eurogenetic S.A., and Richter-Helm BioLogics), three separate active and fully funded P2 trials (US, China and South Korea), and a yea, a peer review that confirms INO-4800 has a ridiculously wonderful safety profile, confirmation that it was immunogenic in 100% of participants, generated neutralizing antibodies, and CD4/CD8 T cell response. So I ask a simple question, “Are the odds not in Inovio’s favor for EUA in 2021?” Whether it be in the US, China or South Korea (or all 3!), INO-4800 will be distributed in 2021 and will for the first time in Inovio’s history generate revenue from the sale of DNA based vaccine that will validate Inovio’s platform and form a foundation for exponential growth. Anyone who has accumulated shares of INOVIO over the years or who happened to get in this year at a high of $33.79 on 6/26/20, will never look back as this revolutionary DNA medicine platform receives proper valuation. While INO-4800 is the flashy, dare I say sexy product, it’s the total pipeline of 12 different products for HPV (3), Immuno-Oncology (2), Infectious Diseases (6) and dMAb (2, Zika, INO-4800) that are at various stages of clinical trials that are the foundation for exponential growth. So thank you INOVIO for facilitating a wonderful peer review and looking forward to an incredible 2021!!
By Troy
Updated 12/8 Recruiting: P1 Platform Study for Prostate Researching Translational Endpoints Correlated to Response to Inform Use of Novel Combinations (PORTER)
Sponsor:
Parker Institute for Cancer Immunotherapy
Collaborators:
Bristol-Myers Squibb
Celldex Therapeutics
Cancer Research Institute, New York City
Inovio Pharmaceuticals
Oncovir, Inc.
Information provided by (Responsible Party):
Parker Institute for Cancer Immunotherapy
Brief Summary:
This study is designed to evaluate multiple clinical hypotheses and mechanistically-defined combinations to evaluate the safety and efficacy of immunotherapy combinations in participants with mCRPC who have received prior secondary androgen receptor signaling inhibitor therapy (eg, abiraterone, enzalutamide, apalutamide).
Treatment:
Drug: NKTR-214 (Cohort A)
Drug: Nivolumab (Cohort A, B and C)
Radiation: Stereotactic body radiation therapy (SBRT) (Cohort B)
Drug: CDX-301 (Cohort B and C)
Drug: Poly-ICLC (Cohort B)
Drug: INO-5151 (Cohort C)
Device: Cellectra 2000
https://clinicaltrials.gov/ct2/history/NCT03835533?A=11&B=12&C=merged#StudyPageTop
12/23 Completed, Has Result: Study of HPV Specific Immunotherapy in Participants With HPV Associated Head and Neck Squamous Cell Carcinoma
This is a Phase I/IIa, open-label, study to evaluate the safety, tolerability, and immunogenicity of INO-3112 [6 mg of VGX-3100 (2 separate DNA plasmids respectively encoding E6 and E7 proteins of HPV 16 and HPV 18) and 1 mg of INO-9012 (DNA plasmid encoding human interleukin 12)] delivered by electroporation (EP) in up to 25 (twenty-five) participants with HPV positive head and neck cancer. The immunotherapy was studied in the following two groups of participants:
Participants who received immunotherapy before and after definitive surgery (Cohort I)
Participants who received immunotherapy at least 2 months after chemoradiation therapy (Cohort II).
Locations
United States, Pennsylvania
University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
Sponsors and Collaborators
Inovio Pharmaceuticals
University of Pennsylvania
Investigators
Study Director: Jeffrey Skolnik, MD Inovio
https://clinicaltrials.gov/ct2/history/NCT02163057?A=11&B=12&C=merged#StudyPageTop
there are also reports that the infectivity of the mutant strain of "VUI-202012/01 (B.1.1.7)" recently appeared in the UK has increased by 70%. This strain has an amino acid mutation at the binding interface between S protein and human ACE2 protein, as well as some other key mutations, which may cause changes in the binding ability of neutralizing antibodies produced by vaccines against S protein. Will it lead to partial vaccine effects? The reduction requires further data analysis.
As long as the main gene sequence and protein levels of the virus have not fundamentally changed, the vaccine will be no problem in dealing with these mutated viruses in the next few years.
Some time ago, the Cell sub-Journal published a study that the new coronavirus D614G mutation not only did not affect the vaccine protection effect, but was more sensitive to the vaccine.
This is why Ino-4800’s “T-cell response were observed to multiple regions of spike protein including the RBD region: 100% of 2mg group” can protect against mutants. Huge selling point!!
investorshub.advfn.com/boards/read_msg.aspx?message_id=160422021
100% immunogenic response, 100% balanced cellular and humoral response, 84% antibodies and 100% T Cells (2.0mg), best in class safety and thermostability.
CD8+ T-cell is responsible for length of immunity, cellular response hunting to kill virus in infected cells.
CD4+ T-cell increases B helper cell production to boost humoral response.
Now apply known durations and long term protection of 4700, there is concern on length of protection with both MRNA and PFE, along with the adverse side effects they have, and tell me MRNA and PFE is still better. I'm not buying it.
Inovio announced the publication of peer-reviewed Phase 1 clinical data from the first cohort of 40 participants for its COVID-19 DNA vaccine candidate, INO-4800, in EClinicalMedicine, an open access clinical journal published by The Lancet. The paper, titled "Safety and immunogenicity of INO-4800 DNA vaccine against SARS-CoV-2: a preliminary report of an open-label, Phase 1 clinical trial," found that INO-4800 was immunogenic in all vaccinated subjects, effectively generating an immune response of humoral and/or cellular responses. Additionally, Phase 1 clinical data found INO-4800 to have a favorable safety and tolerability profile with no serious adverse events reported; only six Grade 1 adverse events were observed, primarily minor injection site reactions. Notably, these only occurred on the day of the first or second dosing, and the AEs did not increase in frequency with the second administration. INO-4800, beyond being safe and tolerable, is stable at room temperature for more than a year, at 37o C (98.6o F) for more than a month, has a five-year projected shelf life at normal refrigeration temperature and does not need to be frozen during transport or storage - all critical factors for timely global distribution in the fight against COVID-19.
Deep Dive on Lancet P1PR: safe booster; T-cell response were observed to multiple regions of spike protein including the RBD region: 100% of 2mg group; neutralizing antibodies: 84% of 2mg group; seroconversion: 95% in both groups; immunogenicity: All 38 have balanced cellular and humoral immune responses; Wk8: 6 Grade 1 AEs
Inovio gains 9% pre-market after positive peer-reviewed data for COVID-19 jab
[On 12/23/20 I posted “BM just said a few more days. That could mean Lancet who publishes online every Saturday.
Together with imminent P2s fully enrolled in China and US, Hope pps reacts well. What’s your opinion of BM now? It looks like 2mg may be selected for P3.]
Dec. 24, 2020 9:28 AM Inovio Pharmaceuticals, Inc. (INO)
By: Dulan Lokuwithana, SA News Editor
Inovio Pharmaceuticals (NASDAQ:INO) has climbed 9.0% in the premarket after the medical journal, The Lancet, published the Phase 1 clinical trial data of its COVID-19 vaccine candidate, INO-4800.
In June, the company announced positive interim Phase 1 data for INO-4800 indicating 94% of immunogenicity of 40 healthy trial participants aged 18 to 50 years.
According to the journal report, 38 trial subjects have received both doses, and 100% (38/38) of them have achieved the immunogenicity with excellent safety and tolerability profile, with either or both humoral or cellular immune responses.
Phase 1 data have suggested the vaccine could be a safe booster, and one of the volunteers in the 1.0mg dose group has become seropositive at baseline due to prior infection with COVID-19. Notably, despite receiving both doses, the individual has not developed any adverse events.
Yet, the report highlights the need for a larger sample size and the inability to conclude the length of the vaccine-driven immunity.
Early December, Inovio announced the initiation of the Phase 2 portion of Phase 2/3 trial for the vaccine in a trial involving 400 individuals aged 18 years or older.
Lancet paper: what’s your opinion and theory on the publication history?
Published: December 23, 2020
Accepted: December 2, 2020
Received in revised form: November 25, 2020
Received: October 16, 2020
Thirty-nine subjects completed both doses. One subject in the 2.0 mg group discontinued trial participation prior to receiving the second dose due to lack of transportation to the clinical site; discontinuation was unrelated to the study or the dosing. One subject was deemed to be seropositive at trial entry.
The 1.0 mg and 2.0 mg dose group both demonstrated seroconversion in 95% of the subjects, respectively, with 78% demonstrating neutralizing antibodies in the 1.0 mg dose group and 84% demonstrating neutralizing antibodies in the 2.0 mg dose group.
Cellular (T cell) response were observed to multiple regions of the spike protein including the RBD region. 74% had measurable cellular responses at the 1.0 mg dose group and 100% of the subjects in the 2.0 mg dose group demonstrated cellular responses.
Through week 8, no serious adverse events were reported. Only 6 related Grade 1 adverse events in 5 subjects were observed, primarily mild injection site reactions (e.g., redness); none of these increased in frequency with the second administration.
All 38 subjects who were evaluable for immunogenicity had balanced cellular and humoral immune responses following the second dose of INO-4800.
CDC said just 1,008,025 shots had been administered as of 9 a.m. ET on Wednesday. That’s roughly 19 million doses shy of earlier projections from public health officials for December.
It leaves public officials less than two weeks — about 8 days — to try to close that gap. Two vaccines – from Pfizer and Moderna – have been authorized for use by the Food and Drug Administration, and the U.S. has shipped a total of 9,465,725 doses across the nation, according to CDC data.
National Institutes of Health Director Dr. Francis Collins said that if the U.S. government doesn’t meet its vaccine goal by the end of this month, he hopes Americans “will understand this is a logistic challenge of enormous proportion.”
“Frankly, I think it’s pretty amazing it has gone as fast as it has, recognizing it has only been 10 days since the FDA gave its first approval for emergency use of the Pfizer vaccine and then a week later for Moderna,” Collins told CNN.
12/23 Just received my 1st round of INO-4800 in Phase 2. Got the dose in BOTH arms. No pain with the Cellectra devise. It was 2 short bursts that felt like one of those home muscle stimulators-but very light. Pain level from 1 to 10 was a zero. Zero reactions after the dose. Going to do my work out later today!
By Due Dilligence
A needle in the skin to make a pimple. Then two jolts from Cellectra 2000 to get the dna in through the cell walks. Took 90 seconds from start to finish on one arm.
@Scott Long
Placebo Comparator: Phase 3: Placebo Optimum Dose Group
Participants will receive either one or two ID injections of placebo based on results from Phase 2 segment, followed by EP using the CELLECTRA® 2000 device on Day 0 and Day 28.
Could Merck acquire Inovio for dAMb, INO-4800, deep pipeline using the same playbook? OWS bets $356M to mass manufacture a Merck drug for severe Covid-19
December 23, 2020 07:19 AM EST
The White House is betting big on a new type of treatment for Covid-19, a drug that results from one late-stage trial suggesting it could drastically improve patients’ odds of recovery from severe disease.
HHS and the Department of Defense announced a $356 million deal to mass manufacture MK-7110, the immune system modifying antibody that Merck acquired in their surprise $425 million buyout of OncoImmune last month. The deal would allow Merck to produce between 60,000 and 100,000 doses of the drug by June 2021.
The new deal is in keeping with the government’s now long-running goal of finding drugs that could help the sickest Covid-19 patients. They initially bet heavily on repurposed antibodies such as IL-6 blockers from Regeneron and Roche, but largely came up empty.
MK-7110, by contrast, was shown to reduce the risk of respiratory failure or death by 50% in a trial of 203 late-stage patients, OncoImmune announced in September. It also appeared to give patients 60% odds of improving.
Although cross-trial comparisons are inherently fraught, the figures would make it as good or better at helping severe patients than dexamethasone, the generic steroid that has thus far been the only drug shown to improve mortality in Covid-19 patients. Both drugs employ different mechanisms of modulating a haywire immune system, which doctors believe is responsible for the virus’ worst symptoms.
Merck, which has been playing catch-up to other drugmakers throughout the pandemic, bought out OncoImmune with the stated purpose of helping scale up the drug. Antibodies are difficult to manufacture on a dime, and the small biotech said they would need substantial help to bring the therapy to anywhere near the scale needed to make a dent on the pandemic.
The DNA vaccine can be regarded as the blueprint of the vampire parts mold . Its early development is fast, the safety is high, the production is relatively easy and the output is large. However, this technical route has not been verified. If approved, it will be the first vaccine of this technical route.
The main foreign player is INOVIO, while the main domestic player is Ai Di Weixin, a company based in Jingwei.
Ai Di Weixin is a representative company of a new generation of vaccines in China and a leader in DNA vaccines in China . The company cooperated with INOVIO, a leading international DNA vaccine company, to develop the urgently needed new crown vaccine, providing a safe and efficient new technical route for the global epidemic.
The INOVIO new crown vaccine has now completed the first phase of clinical trials, and the second phase of clinical trials in the United States is in progress. Ai Di Weixin has completed the first phase in China, and the second phase has been completed. It is expected to be approved for listing next year.
As far as safety is concerned, the DNA vaccine developed by INOVIO and Ai Diweixin currently seems the most reliable. It is understood that this vaccine produces almost no level 2 side effects, and almost all side effects are level 1 (mild) side effects.
In comparison, according to the currently published data, vaccines developed by AstraZeneca, J&J, and CanSino Bio have a certain gap in effectiveness and safety from leading vaccines.
The production of the convenience and safety of DNA vaccines INOVIO Aidi Wei Yan and R & D are high, storage and transport of difficulty are small, can be stored at room temperature for 5 years, helped to popularize the new crown vaccine. Its production capacity is 100 million a year.
Pfizer/BioNtech’s mRNA vaccine is priced at US$19.5, but the price of US$19.5/dose is limited to the United States. Pricing strategies in other countries will take into account the principles of quantity, pre-commitment, fairness, and affordability. Its production capacity is 1.3 billion pieces per year.
However, as mentioned above, because mRNA vaccines are difficult and costly to produce, and are relatively unstable, the storage conditions for the vaccine are very strict. It can be stored at -70°C for 6 months. It can be stored in a general hospital refrigerator 2 It can only be stored for 5 days at -8°C, which requires strict storage and transportation .
This puts forward requirements for the upgrading of equipment for hospitals and pharmacies, because hospitals are usually not equipped with ultra-low temperature freezers, and the ultra-low temperature freezers, usually priced as high as 30,000-100,000 yuan, are not friendly to medical institutions in developing and poor countries.
As far as China is concerned, cold chain resources are lacking. The total amount is 2.5 times lower than that of the United States, and the average per capita is 10 times lower than that of the United States. The market share of the number one pharmaceutical cold chain company in China is less than 6%, and about 90% of the pharmaceutical cold chain Use ice cubes instead. Therefore, low-temperature storage is likely to become a bottleneck for the popularization of such vaccines in China.
How long is the protection period of the new crown vaccine?
For the new crown vaccine, an important unanswered question of public concern is-how long can the protection provided by the vaccine last?
Previously, the top medical journal "New England Journal of Medicine" (NEJM) published a number of articles in letter format, which mainly discussed the gradual disappearance of antibodies in patients with moderately ill new coronary disease. This also means that the body's immunity to the new coronavirus may not last. Later, another case was infected with the new crown, which cast a shadow over the application of the new crown vaccine.
The duration of protection of different vaccines varies. In accordance with the requirements of the "Technical Guidelines for the Development of New Coronavirus Preventive Vaccines (Trial)" issued by the Drug Evaluation Center of the National Medical Products Administration of China, the vaccine should provide protection for 1 year or more and at least 6 months of protection.Its protection durability research can accumulate data through continuous human trials or animal studies after the market.
Ultimately, the duration of vaccine protection will also become one of the important criteria for vaccine competition.
there are also reports that the infectivity of the mutant strain of "VUI-202012/01 (B.1.1.7)" recently appeared in the UK has increased by 70%. This strain has an amino acid mutation at the binding interface between S protein and human ACE2 protein, as well as some other key mutations, which may cause changes in the binding ability of neutralizing antibodies produced by vaccines against S protein. Will it lead to partial vaccine effects? The reduction requires further data analysis.
As long as the main gene sequence and protein levels of the virus have not fundamentally changed, the vaccine will be no problem in dealing with these mutated viruses in the next few years.
Some time ago, the Cell sub-Journal published a study that the new coronavirus D614G mutation not only did not affect the vaccine protection effect, but was more sensitive to the vaccine.
Can the new crown vaccine prevent the disease or the infection?
This issue is still inconclusive. The key point is whether vaccines can effectively reduce asymptomatic infections. A vaccine that can prevent asymptomatic infections may be the key to reversing the course of the new coronary pneumonia pandemic.
Whether other vaccines can reduce asymptomatic infections will also be an important competition indicator.
https://mdr24olj2oojzvy3d3bybnpopy-adwhj77lcyoafdy-finance-sina-cn.translate.goog/tech/csj/2020-12-23/detail-iiznctke8031610.d.html?fromtech=1&from=wap
12/21/20 IU PR: Inovio, AZN, IU, W, $37.6M grant awarded to develop innovative COVID-19 treatment, start Jan 2021
FOR IMMEDIATE RELEASE
Dec. 21, 2020
BLOOMINGTON, Ind. -- While the world is focused on the promise of the COVID-19 vaccines now being released, researchers continue to look for new and innovative ways to fight the pandemic. Indiana University is part of a consortium -- including AstraZeneca, the Wistar Institute, Inovio and the University of Pennsylvania -- that just received a $37.6 million grant to develop and study DNA-encoded monoclonal antibodies as an additional way to fight SARS-CoV-2, the virus that causes COVID-19.
The grant, awarded from the Defense Advanced Research Projects Agency and the Joint Program Executive Office for Chemical, Biological, Radiological and Nuclear Defense, will enable IU and its consortium partners to take its DNA-encoded monoclonal antibodies from the design stage into human phase II clinical trials in the next two years. The technology works by providing the genetic information the body needs to produce its own antibodies against a bacteria or virus, such as SARS-CoV-2.
IU's role in this research study -- under the leadership of Jesper Pallesen, assistant professor of molecular and cellular biochemistry in the College of Arts and Sciences at IU Bloomington -- will be focused on the structural analysis of the DNA-encoded monoclonal antibodies, known as DMAbs, from the design phase all the way through to human clinical trials.
"My lab specializes in structure-guided vaccine and therapeutics design," Pallesen said. "As part of the consortium, we'll be evaluating how and where our DMAbs bind to the surface proteins of SARS-CoV-2."
To do this, Pallesen and his team will use cryo-electron microscopy, which enables them to see, atom by atom, how proteins and viruses are built. He will use this technology to view all samples of the DMAbs produced by the consortium starting as early as January.
As well as simply being another weapon in the fight against COVID-19, DNA-encoded monoclonal antibodies technology holds many advantages. It's highly specific to the virus it's protecting against, it's quick to manufacture with a low cost of production, and it does not need special cold storage. In addition, DMAbs can introduce antibodies independently of the patient's own immune response.
"Our technology does not rely on the continual development of a patient's own immune response to react to SARS-CoV-2 but rather independently creates a recipe for an optimal response," Pallesen said. "I am really excited to help advance DNA-based therapeutics and vaccines against SARS-CoV-2 and beyond. The distribution advantages of DNA technologies are indisputable, and we have the potential to bring therapeutics and vaccines to people much faster and -- perhaps most importantly -- to parts of the world that are currently very challenging to service."
IU Research
IU's world-class researchers have driven innovation and creative initiatives that matter for 200 years. From curing testicular cancer to collaborating with NASA to search for life on Mars, IU has earned its reputation as a world-class research institution. Supported by $854 million last year from our partners, IU researchers are building collaborations and uncovering new solutions that improve lives in Indiana and around the globe.
https://news.iu.edu/stories/2020/12/iub/releases/21-grant-to-develop-innovative-covid-19-treatment.html
Clinical data was published in Vaccines by MDPI which demonstrated that PENNVAX-GP, INOVIO's DNA vaccine against HIV-1, was safe, tolerable, and acceptable in healthy adults
Intramuscular and Intradermal Electroporation of HIV-1 PENNVAX-GP® DNA Vaccine and IL-12 Is Safe, Tolerable, Acceptable in Healthy Adults
Vaccines 2020, 8(4), 741; https://doi.org/10.3390/vaccines8040741
Received: 11 October 2020 / Revised: 1 December 2020 / Accepted: 2 December 2020 / Published: 7 December 2020
Background: Several techniques are under investigation to improve the immunogenicity of HIV-1 DNA vaccine candidates. DNA vaccines are advantageous due to their ease of design, expression of multiple antigens, and safety. Methods: The HVTN 098 trial assessed the PENNVAX®-GP DNA vaccine (encoding HIV env, gag, pol) administered with or without plasmid IL-12 at 0-, 1-, 3-, and 6-month timepoints via intradermal (ID) or intramuscular (IM) electroporation (EP) in healthy, adult participants. We report on safety, tolerability, and acceptability. Results: HVTN 098 enrolled 94 participants: 85 received PENNVAX®-GP and nine received placebo. Visual analog scale (VAS) pain scores immediately after each vaccination were lower in the ID/EP than in the IM/EP group (medians 4.1–4.6 vs. 6–6.5, p < 0.01). IM/EP participants reported greater pain and/or tenderness at the injection site. Most ID/EP participants had skin lesions such as scabs/eschars, scars, and pigmentation changes, which resolved within 6 months in 51% of participants (24/55). Eighty-two percent of IM/EP and 92% of ID/EP participant survey responses showed acceptable levels of discomfort. Conclusions: ID/EP and IM/EP are distinct experiences; however, HIV-1 DNA vaccination by either route was safe, tolerable and acceptable by most study participants.
12/22 What’s in the $900 Billion Covid-19 Relief Bill. States and federal agencies would receive funding for vaccine distribution. About $20 billion would go to the Biomedical Advanced Research and Development Authority, or BARDA, for procuring vaccines and therapeutics. Nearly $9 billion would go to the Centers for Disease Control and Prevention and states for further distribution of the vaccine, and $3 billion is designated for the national stockpile. Included in those sums is $300 million that is directed to go to high-risk areas and to communities of color.”
https://www.wsj.com/articles/what-is-in-the-900-billion-covid-19-aid-bill-11608557531
Ino has had strong relationship with DoD, DARPA. Most likely, BARDA will procure INO-4800 too.
INOVIO to Develop DNA-encoded Monoclonal Antibody (dMAb®) Candidates to Treat COVID-19 with Funding from the Defense Advanced Research Projects Agency (DARPA) and the Department of Defense's (DoD) Joint Program Executive Office for Chemical, Biological, Radiological and Nuclear Defense (JPEO-CBRND)
December 15, 2020
INOVIO Receives $71 Million Contract From U.S. Department of Defense To Scale Up Manufacture of CELLECTRA® 3PSP Smart Device and Procurement of CELLECTRA® 2000 for COVID-19 DNA Vaccine
June 23, 2020
Forbes12/22: The Moderna Vaccine’s Antibodies May Not Last As Long As We Hoped
While only a preliminary analysis, a new study by the New England Journal of Medicine (NEJM) suggests that the long-term efficacy of Moderna’s mRNA-1273 vaccine, specifically the neutralizing antibody count, may be less than we were hoping for.
Neutralizing antibodies bind to invading pathogens, like all antibodies do, but they bind in a manner that stops infection. That is why pharmaceutical companies stress neutralizing antibody counts as an essential measure for their vaccines’ success.
The NEJM study followed a group of 34 patients who had taken both doses of mRNA-1273 and analyzed their antibody counts from the administration of the first dose for 119 days. Neutralizing antibodies were monitored in subgroups of 18-55 years of age, 56-70, and 71+, as shown below.
A significant determinant of vaccines’ effectiveness in controlling a pandemic is antibody duration—how long the antibodies last in a person’s system. For those 18-55 years old, the majority only show a slight decrease in neutralizing antibodies in the three months following their second vaccine dose. Two of the 34 patients in this age group saw a significant drop in neutralizing antibodies. Due to the limited number of participants in this study, we cannot draw conclusions from these outliers until further data becomes available.
However, sustained antibody counts are not the case in the 56-70 and 71+ age groups. In these subsets, the neutralizing antibody counts fall anywhere between 50 and 95 percent. This suggests that in these age groups, the duration of neutralizing antibodies from the Moderna vaccine will be relatively short, potentially less than a year. That is particularly troubling as these are the age groups most affected by severe Covid-19. It may well be that the levels of antibodies after three months, if maintained, are sufficient to protect these age groups, but it is unlikely they will continue to protect if levels fall still further.
Moderna is simultaneously producing vaccines for avian influenzas H10N8 and H7N9. These two vaccine candidates show similar drops in neutralizing antibody counts to mRNA-1273 after three months. According to data from Science Direct, antibodies persisted up to six months after injection, but dropped as much as 90% in that time. Sustained protection from the virus requires sustained neutralizing antibodies, yet the patterns indicate that Covid-19 vaccines may be more than a one-time occurrence.
In addition to Moderna’s bird flu vaccines presenting similar antibody trends to that of the Covid-19 vaccine, early trials required them to discontinue their 400 microgram dose due to patient side effects like injection site irritation and headaches. The mRNA-1273 vaccine will be two doses of 500 micrograms each, according to the CDC. While Moderna trials did note significant side effects from vaccine administration, some effects may arise in the general population.
This is all not to say Moderna’s vaccine is not effective. Even at these low numbers, antibodies may still be fully or partially protective. That remains to be seen. Additionally, the NEJM study only analyzes 34 patients, most of whom are in the 18-55-year-old age group. Conclusions drawn from such small data sets must be taken with a pinch of salt, but we still need to take the results seriously—this data may be the first of many indicators that vaccines don’t last as long as we would hope.
It is also vital to review similar data in the Pfizer and Biotech vaccines as it becomes available. The United States government and the governments of countries worldwide seem to be banking on the effectiveness of these vaccines. We urge pharmaceutical companies to be forthcoming on their continued monitoring of these early patients and those who have received the vaccine more recently. As more data like this is released, the clearer the picture of these next several months of the pandemic becomes.
The Stimulus bill is now on the Presidents desk ready to be sign into law today.
The house passed the bill yesterday evening (359 - 53 vote)
The Senate passed the bill just hours later (92 - 6 vote)
Of the $900+ Billion stimulus package $28 Billion is earmarked for Vaccines!!
Of the $28 Billion = $8 Billion is for vaccine distribution and an additional $20 Billion is for vaccines.
GAVI is getting $3.36 Billion for vaccines to 3rd world countries. GAVI is who is funding COVAX.
Inovio is working with GAVI, COVAX, CEPI and Bill and Malinda Gates foundation to help vaccinate the 3rd world countries.
Note: Money for vaccines from Pfizer, Moderna, J&N, AZN and Novavax was already funded back in March through the Cares Act. This $20 Billion is additional money for vaccines!!!
Tons and Tons of money is going start flowing back into vaccines companies!!!!! Tier 2 vaccine companies this time will get attention.
DoD has already started paying on the $71 million. The $71 million is a T&M contract (time and material not lump sum contract). That means Inovio invoices the DOD as it acquires costs. Its shown in Inovio's 10K the last two quarters. I am sure you read it. You may have just not realized it.
Plan accordingly.
By AT
Breaking News: INNOVATE Update UPenn, Thomas Jefferson University status changed to Recruiting
Last Update Submitted that
Met QC Criteria: December 4 => 16, 2020
Last Update Posted: December 8 => 18, 2020 [ Actual Estimate]
University of Pennsylvania
[ Not yet => Recruiting]
Philadelphia, Pennsylvania, United States, 19104
Contact: Program Manager Amanda Bear PennCovidVaccine@pennmedicine.upenn.edu
Principal Investigator: Pablo Tebas
Thomas Jefferson University
[ Not yet => Recruiting]
Philadelphia, Pennsylvania, United States, 19107
Contact: Principal Investigator Christopher Chambers Christopher.Chambers@jefferson.edu
https://clinicaltrials.gov/ct2/history/NCT04642638?A=3&B=4&C=merged#StudyPageTop
FDA is investigating allergic reactions to COVID vaccine in multiple states - as one Chicago hospital pauses its program after four workers suffer ill-effects - and CDC issues new guidelines for those with allergies
By Matthew Wright and Ariel Zilber For Dailymail.com and Associated Press and Reuters
00:49 20 Dec 2020, updated 04:55 20 Dec 2020
CDC confirms at least six have had adverse reactions to COVID-19 vaccine
So far, some 272,000 shots of Pfizer-BioNTech vaccine have been given in US
In Alaska, three health care workers needed medical attention after getting shot
In Chicago suburb, hospital stopped inoculations after four had severe reaction
FDA official says allergic reactions could be due to polyethylene glycol (PEG)
PEG is a chemical compound present in both Pfizer and Moderna vaccines
PEG is also found in laxatives as well as creams, ointments, and solvents
In industrial use, PEG is also a binding agent that can be found in antifreeze
FDA insists most Americans with allergies should be safe to get the vaccine
US health officials closely tracking possible side effects of the first authorized COVID-19 vaccine said on Saturday they have seen at least six cases of severe allergic reactions out of more than a quarter million shots given - prompting one Illinois hospital to pause vaccinations.
Medical experts said that a chemical called polyethylene glycol (PEG), a compound most commonly used in laxatives, 'could be the culprit' causing the reactions.
PEG is an ingredient in the Pfizer vaccine as well as the Moderna Inc vaccine authorized on Friday.
But the Food and Drug Administration has said that most Americans with allergies should be safe to receive the vaccine. It said only people who have previously had severe allergic reactions to vaccines or ingredients in this particular vaccine should avoid getting the shot.
https://news.google.com/articles/CAIiECvveLLsl7EQNU7MgDRgsEEqGQgEKhAIACoHCAowzuOICzCZ4ocDMPvTpwY?hl=en-US&gl=US&ceid=US%3Aen
Ino, Advaccine to announce P2’s are fully enrolled in US and China in the next 8 biz days. All 400 and 640 participants respectively receive first dose. 2 shot will finish 1/21. 6 wk data readout 3/4.
The Phase 2 clinical trial being conducted in China is independent of the INNOVATE Phase 2/3 clinical trial of INO-4800 being advanced in the U.S. and will enroll approximately 640 participants who are 18 years or older. Advaccine is conducting and funding the Phase 2 trial in China, which is expected to fully enroll by the end of this month.
Ben said P1PR will be published online before EOY. NEJM next dates are 12/23, 12/30.
Now that Ben Matone emailed: “2000 will likely be used in P3. 3P metrics/data will be applied to the BLA Filing and used for
commercialization/distribution. DoD is providing funding for both 2000 and 3P per the announcement in June,”, P3 hold May be lifted soon as 2000 has been approved to be used In Ino-4800 P2 and Many other clinical trials before.
2000 ‘s advantage is it has obtained CE Mark, Europe highest medical device standard. Therefore, 2000 can be applied For EUA in Europe.
JK appears to Back off from pushing 3P for P3 to make up for lost time and get large CEPI manufacturing scale-up funding upon P3 FDA IND OK.
With P3 OK, Ino can start P3 in March, ahead of Q2 schedule.
JK is incentivized to roll into P3 ASAP in March to get vaccine order from COVAX’s second billion doses, DoD, Taiwan, China, Korea, India, LMICs (Low and Mid-Income Countries).
Lassa Fever first shot PR.
12/18 Ben Matone emailed: 2000 will likely be used in P3. 3P metrics/data will be applied to the BLA
Filing and used for commercialization/distribution. DoD is providing funding for both 2000 and 3P per the announcement in June, along with covering the costs for P2/3 clinical trial with Ino-4800 for COVID-19.
https://stocktwits.com/Freethinker83
He basically tipped off P3 hold will be lifted soon.
Gorester
02:03 PM
returned home from my double arm p2 .
The worst part was giving blood. 14 tubes ( 7 large ones )
Each arm received 1 intradermal and electro device application.( no pain what so ever )
I return in 28 days for the second rd.
The trial at this location (Tampa) was filled.
Got the impression I was last or close to last to get the 1 st shot.
Also got the impression I was lucky to get both arms,thinking I got the Vac.
I have no swelling or pain.
i do not feel any effects ( just got 6 hrs ago )
no pain no swelling.
Sure hope I got the Vac,why would they do both arms for the placebo?
They said they had over 50 people in for qualifying blood work.
75% get real vaccine, 25% placebo. That goes for both single arm people 1mg and 2 arm 2mg people.
So we have 75% chance we got the real vaccine.
we’re calculating to have about 1,000 handheld devices, one device to deliver about thousand doses in the field. Each device can deliver up to 5,000 or more doses and we’re putting in a high scale manufacturing lines to help us to do that starting 2021, the actual needle parts what we call the arrays are single use, so they have to match the number of doses. Again with the leverage of DoD funding that we announced in the summer, we’re able to put in automated manufacturing lines both here in the U.S. and eventually ex-U.S. to scale-up the array manufacturing.
Inovio Pharmaceuticals, Inc. (INO) President & CEO Joseph Kim Presents at Oppenheimer Fall Healthcare Life Sciences & MedTech Summit Transcript
Sep. 23, 2020 2:06 PM
Robert stated the CELLECTRA 2000 device is their early stage work horse and that the new CELLECTRA 3PSP was made to be extremely portable using batteries, cleanable, re-usable, for intradermal doses. The device is being made to used globally with different labels and languages.
investorshubDoTadvfnDoTcom/boards/read_msg.aspx?message_id=159869682
Robert stated that there are no issues getting booster vaccines. He mentioned some patients for GBM received 10-11 booster doses with no issues.
He also stated that after a patient receives DNA doses, the vaccine is cleared out of the body in a very short period time, less than a couple days.
The questioned was asked if INOVIO has been looking at using nanoparticle DNA vaccines. The answer was no, because electroporation is a very very effective and efficient method. For cancers, the cure is injected in larger doses intramuscularly, and for vaccines into the skin intradermally.
23K participants, Ino-4500, $26M CEPI-funded, Largest-ever Lassa fever research programme launches in West Africa
December 18, 2020, Oslo, Norway and Abuja, Nigeria – The largest-ever Lassa fever research programme in West Africa has been launched in Nigeria by the Coalition for Epidemic Preparedness Innovations (CEPI), the Nigeria Lassa Fever Research consortium consisting of the Nigeria Centre for Disease Control (NCDC), and supporting partners, to provide a more accurate estimate of the incidence of the deadly haemorrhagic disease across the region. Supported through US $26 million in funding from CEPI, up to 23,000 participants across Nigeria and, in later weeks, four other outbreak-prone countries—Benin, Guinea, Liberia, and Sierra Leone—will take part in the programme, named ‘Enable’, over the next 24 months.
Due to significant variability and severity in symptoms, and lack of formal and standardised diagnoses, the true case count of those who have or have previously suffered from Lassa fever infection in West Africa is likely much higher than current estimates of 100,000 to 300,000 cases per year. The aim of this multi-country research effort is to therefore build on existing local Lassa fever research and surveillance and provide an update to existing research on the number of people infected with the disease. Findings should also highlight any differences in the age and gender of people getting infected and provide a more accurate overview on the proportion of asymptomatic and symptomatic cases.
Such data will be critical in guiding decisions on the design of future late-stage efficacy trials to evaluate potential Lassa vaccine candidates. As a leading funder of Lassa vaccine development, CEPI has supported the development of six Lassa vaccine candidates to date- with two vaccines, developed by CEPI partners Inovio and Themis Bioscience, entering clinical trials last year.
https://cepi.net/news_cepi/largest-ever-lassa-fever-research-programme-launches-in-west-africa/
COVAX announces additional deals to access promising COVID-19 vaccine candidates; plans global rollout starting Q1 2021
Geneva/Oslo, 18 December 2020
Given these are arrangements for 2 billion doses of vaccine candidates which are still under development, COVAX will continue developing its portfolio: this will be critical to achieve its goal of securing access to 2 billion doses of safe and effective, approved vaccines that are suitable for all participants’ contexts, and available by the end of 2021. However, today’s announcements offer the clearest pathway yet to end the acute phase of the pandemic by protecting the most vulnerable populations around the world. This includes delivering at least 1.3 billion donor-funded doses of approved vaccines in 2021 to the 92 low- and middle-income economies eligible for the COVAX AMC.
The new deals announced today include the signing of an advance purchase agreement with AstraZeneca for 170 million doses of the AstraZeneca/Oxford candidate, and a memorandum of understanding (MoU) with Johnson & Johnson for 500 million doses of the Janssen candidate, which is currently being investigated as a single dose vaccine.. These deals are in addition to existing agreements COVAX has with the Serum Institute of India (SII) for 200 million doses – with options for up to 900 million doses more – of either the AstraZeneca/Oxford or Novavax candidates, as well as a statement of intent for 200 million doses of the Sanofi/GSK vaccine candidate.
In addition to this, COVAX also has – through R&D partnership agreements – first right of refusal in 2021 to access potentially more than one billion doses (based on current estimates from the manufacturing processes under development) that will be produced, subject to technical success and regulatory approval, by candidates in the COVAX R&D Portfolio.
Given these are arrangements for 2 billion doses of vaccine candidates which are still under development, COVAX will continue developing its portfolio: this will be critical to achieve its goal of securing access to 2 billion doses of safe and effective, approved vaccines that are suitable for all participants’ contexts, and available by the end of 2021. However, today’s announcements offer the clearest pathway yet to end the acute phase of the pandemic by protecting the most vulnerable populations around the world. This includes delivering at least 1.3 billion donor-funded doses of approved vaccines in 2021 to the 92 low- and middle-income economies eligible for the COVAX AMC.
Today’s announcements on deals and dose-sharing mean COVAX can plan for the first deliveries of vaccines in the first quarter of 2021, with the first tranche of doses – enough to protect health and social care workers – delivered in the first half of 2021 to all participating economies who have requested doses in this timeframe. This would be followed by further delivery of doses to all participants in the second half of the year – targeting supply of doses equalling up to 20% of participants’ populations (or a lower amount if requested by the participant) by the end of the year. Additional doses to reach higher coverage levels will then be available in 2022. All deliveries are contingent upon several factors, such as regulatory approvals and country readiness.
To achieve this ambitious goal, COVAX currently estimates it needs to raise an additional US$ 6.8 billion in 2021 – US$ 800 million for research and development, at least US$ 4.6 billion for the COVAX AMC and US$ 1.4 billion for delivery support.
Support for the COVAX AMC will be critical to ensuring ability to pay is not a barrier to access. Thanks to the generous support of sovereign, private sector, and philanthropic donors, the AMC has met its urgent 2020 fundraising target of US$ 2 billion, but at least US$ 4.6 billion more is needed in 2021 to procure doses of successful candidates as they come through the portfolio.
The last two weeks have seen a number of pledges made to Gavi for the COVAX AMC, bringing the overall amount raised to US$ 2.4 billion:
https://cepi.net/news_cepi/covax-announces-additional-deals-to-access-promising-covid-19-vaccine-candidates-plans-global-rollout-starting-q1-2021/
Inovio contracts Kaneka for plasmid DNA COVID vaccine
by Millie Nelson
Thursday, December 17, 2020 6:19 am
Inovio has partnered with plasmid manufacturer Kaneka Eurogentec to support the production of its COVID-19 vaccine candidate, INO-4800.
Kaneka Eurogentec, an affiliate of Kaneka Corporation, will join Inovio’s growing network of contract development and manufacturing organizations?(CDMOs) to support INO-4800, a COVID-19 plasmid DNA-based vaccine, set to move into a Phase II/III clinical trial.
The biotech has not disclosed the terms of agreement. However, Inovio’s CEO, Joseph Kim, said that “Kaneka Eurogentec will be a crucial member of Inovio’s global manufacturing consortium, supporting our plans to produce, manufacture and scale our COVID-19 candidate, INO-4800”.
According to Inovio, the partnership with Kaneka will enhance the stability of INO-4800 and make it a vaccine with a favorable tolerability profile. Lieven Janssens, Kaneka Eurogentec’s CEO, echoed Kim’s statement, expressing his excitement to support Inovio’s “manufacturing needs of DNA medicines and vaccines across Inovio’s platform.”
Kaneka joins Thermo Fisher Scientific, Richter-Helm BioLogics, and Ology Biosciences as third-party manufacturers for the vaccine candidate.
Cold-chain-less
Kim previously told Bioprocess Insider that Inovio’s DNA-based vaccines “are naturally a lot more stable” than other COVID-19 vaccines in development.
INO-4800 is the only nucleic-acid based vaccine that remains stable at room temperature for more than a year, he said. Meanwhile, Inovio has demonstrated other DNA vaccines in its portfolio that have a shelf life greater than five years when refrigerated.
If INO-4800 does reach the market, it may therefore be easier to distribute and administer than some of the other COVID-19 vaccines.
Pfizer/BioNTech’s recently approved mRNA vaccine needs to be kept at temperatures as low as minus 80 degrees Celsius. Moderna’s remains stable at minus 20, but will still require a solid cold-chain logistics network for its distribution.
https://bioprocessintl.com/bioprocess-insider/therapeutic-class/thermo-stability-could-give-dna-vaccine-advantage-in-covid-19-race-says-inovio/
Pfizer asked for an EUA to vaccinate anyone 16 years of age or older, but some members of the committee were concerned that Pfizer did not conduct sufficient testing on 16 and 17 year olds and voted accordingly, even though they supported vaccinating anyone over 18. Moderna only requested an EUA for people 18 and up, assuaging the committee’s concerns.
Nevertheless, some advisory members still sparred with the FDA over the wording of the question put before the committee, fearing that the wording may mislead the public into believing that the vaccine has been fully approved. They offered adding “experimental” or “emergency use authorization” to the question.
“This can be interpreted as recommending full approval,” said NCAT’s Michael Kurilla. “That may… preclude not only adequate evaluation of this vaccine but also future and ongoing Covid vaccines in development.
FDA officials and other members, however, quickly shot down the idea.
“The question is never when do you know everything, it’s when do you know enough,” said Paul Offit, an infectious disease physician at Children’s Hospital of Philadelphia.
Kurilla abstained over the wording, as well as concerns that an expanded access protocol may have been more appropriate than an EUA, allowing trials to continue to collect randomized data.
An EUA for Moderna would roughly double the amount of vaccine immediately available in the U.S., from over 20 million doses to over 40 million doses. The vaccine is also easier to distribute as it can be handled at the same temperature as most approved vaccines — unlike Pfizer’s shot — and the U.S. has exercised options to acquire 200 million doses through June.
While proffering dozens of questions, the committee never expressed serious concerns about the safety or effectiveness of the vaccine. Moderna announced previously that the vaccine was 94.1% effective at preventing symptomatic Covid-19. Although the FDA review revealed that the vaccine appeared less effective in volunteers over 65 — 86.5% protection — company executives noted that the difference was not statistically significant.
Instead, discussion centered on rare potential side effects and Moderna’s plan for what to do with adverse events. The FDA’s review turned up one surprising serious event: Two volunteers who had previously received dermal filling — e.g. botox — experienced facial swelling after receiving the vaccine.
The panel asked repeatedly the allergic reactions that have emerged in the two weeks since Pfizer’s vaccine was inoculated. Although Moderna said they did not see any cases of anaphylaxis in their study — outside of one allergic reaction two months out, from someone with a soy allergy — they also noted it as one potential serious event to monitor long term.
Still, Moderna CMO Tal Zaks cautioned that each component of the company’s lipid nanoparticle, which may have triggered the allergic reaction in Pfizer recipients, was different chemically than the Pfizer-BioNTech vaccine.
“While we all might say, oh there’s an LNP here, there’s a lipid and mRNA, therefore they must be all be the same,” he said. “I would not necessarily assume that.”
The only point of continual friction between Moderna and the panel arose around the question of what the company should do with their Phase III trial after an EUA is issued. The group was skeptical last week when Pfizer proposed gradually unblinding participants as they become eligible for vaccine under CDC priority guidelines. Moderna wanted to go further, immediately offering the vaccine to all placebo participants, regardless of whether they would be eligible.
Moderna executives said that they needed to unblind to prevent volunteers from dropping out of the study, and because placebo participants are and would continue to be infected. They said they could vaccinate them with clinical supply of the vaccine that would not draw from their commercial stable.
“Additional severe cases and death are a question more of when than a question of if,” Moderna senior vice president Jacqueline Miller said.
Many advisors rejected the approach, proposing that Moderna either follow Pfizer’s plan or adopt an approach where the trial would stay blinded but participants in the vaccine arm would get placebo and volunteers in the placebo arm would receive vaccine, allowing comparisons on durability and long-term adverse events. A few, however, backed the Moderna approach, saying the blinding proposal and even the Pfizer approach may be infeasible.
The debate got to the point that at least two different advisors proposed the agency allow the panelists to vote on the issue, although they had not originally been asked to do so.
“It seems to me that there’s an assumption that Moderna is going to do what it’s going to do. It doesn’t have to be that way,” Sheldon Taubman, the consumer advocate on the panel, said. “We weren’t asked to vote on it, but we could vote on it.”
Marion Gruber, director of the offices of vaccine research at the FDA, though, neutralized that idea, citing the “complexity of the situation” and the fact that they did not ask the committee to vote on the same issue at the Pfizer trial. The hearing ended without a resolution.
“I think we gave FDA a sense of our with that we could do a crossover blinded design, but the realization that that may be impossible,” committee chair Arnold Monto said. “FDA will be negotiating with Moderna about the way they will address this problem.”
https://endpts.com/in-historic-vote-mrna-vaccines-go-2-and-0-as-fda-experts-unanimously-back-modernas-covid-19-vaccine/
Ino’s DNA vaccine competition in Korea called Genexine with their GX-19 decided to change their formula to GX-19N and restarting their clinical trials. They initially tried electroporation device and an air injection device but now they decided to go with electroporation device moving forward. This could mean that Inovio is a couple steps ahead of them.
Genexine "Corona 19 Vaccine'GX-19N' Prepares for Variant Virus"
Input 2020-12-17 16:15
Genexine announced on the 17th that it announced the results of phase 1 clinical trials of the COVID-19 prevention vaccine'GX-19' and the upgraded development plan to'GX-19N' at the'Corona 19 Pan-Government Working Committee Vaccine Sub-Conference'.
As a result of the phase 1 clinical trial of GX-19, there were almost no side effects of systemic or severe or more serious side effects, and the incidence of mild adverse reactions was also very low within 5%, confirming superior safety compared to other vaccines. In terms of immunogenicity, antigen-specific T-cell immune responses were higher than those of patients in the recovery phase, and the neutralizing antibody response showed a statistically significant increase after administration compared to the baseline, but lower than those in the recovery phase. Based on these phase 1 results, Genexine selected 3mg and electroporator (EP) as the recommended dose and administration device for the next-stage clinical trial.
Genexine, as a latecomer in the development of the Corona 19 vaccine, decided that GX-19 needs to strengthen its competitiveness, and has revised its development strategy to the next-generation vaccine GX-19N that can prepare for reinfection after the occurrence of a variant of the recently emerged corona virus and recovery.
GX-19N secured excellent safety by using the same platform as GX-19, and additionally loaded Nucleocapsid antigen with high sequence integrity to the existing Spike antigen to respond to strains of the Corona 19 virus or additional pandemic situations. It is a designed vaccine. Through animal experiments, we have confirmed a wide and strong T cell immune response and improved antibody response, and it is being developed as a stable vaccine for more than 3 months at room temperature considering future storage and transportation.
Genexine is focusing on the function of T cells in the development of a vaccine for preventing COVID-19. According to a paper recently published by Public Health England, a UK public medical institution, after a four-month follow-up observation of the correlation between T-cell immune response and COVID-19 defense efficacy in 2826 essential workers of public institutions, the group with low T-cell response was coronavirus I was infected with 19. Even without antibodies, if the T cell response is high, Corona 19 infection does not occur at all, so it was confirmed that the T cell immune response is more important than the neutralizing antibody to sustain the protective effect against Corona 19.
Genexine plans to develop a vaccine that can protect against coronavirus re-infection and mutants based on T-cell immunity, and develop a'game changer vaccine to end the recurring corona 19 infection situation in the future. In order to minimize the delay in the speed of development, after conducting a large-scale clinical trial at the same time in Korea and abroad based on the results of the interim analysis in the later phase 2a, it is applied for emergency use approval.
Seong Young-cheol, CEO of Genexine, said, "The time to enter phase 3 clinical trials may be a little later than we initially planned, but we will repay you with an excellent vaccine."
https://rnglin2geb277rxqjsnwmplesm-adwhj77lcyoafdy-m-etoday-co-kr.translate.goog/view.php?idxno=1975176
Equitable-access-to-vaccines-is-the-best-way-out-of-COVID-19
17 Dec 2020
By Richard Wilder
Firstly, when it comes to making actual vaccine investments, CEPI ensures that the specific characteristics of the vaccine candidates it is supporting align with the WHO’s target product profile for COVID-19 vaccines. In addition to safety and efficacy requirements, this product profile also includes factors that will be crucial for distribution in low-income and middle-income countries (LMICs), such as storage conditions, method and route of administration, cost of goods, and number of doses required (ie, one vs two doses).
Thirdly, CEPI’s R&D investments are closely interlinked with increasing manufacturing capacity to meet global demand and provide doses for fair allocation through COVAX, to reduce the risk of LMICs being left behind in this time of crisis. Early in the pandemic, CEPI identified the urgent need to develop manufacturing capacity in parallel with clinical trials to ensure rapid supply of vaccine once approved by regulators. Therefore, CEPI has made substantial investments, at financial risk, to bolster global vaccine manufacturing capacity. Equitable access has guided these investments too. To date, CEPI has committed over US$1.1 billion in COVID-19 vaccine R&D and manufacturing agreements. If all of these investments yield safe and effective vaccines, based on current estimates from the manufacturing processes under development, COVAX could potentially be given the right of first refusal for over one billion doses of CEPI-funded vaccines. In a world where wealthy countries are competing to secure bilateral agreements with vaccine manufacturers this is critically important to achieving equitable access for all to vaccines.
https://cepi.net/news_cepi/equitable-access-to-vaccines-is-the-best-way-out-of-covid-19/
COVAX Contract Detail with Inovio
Summary of Agreement with Inovio
Scope of agreement
? Vaccine Development
Scale-up of manufacturing
Supply of vaccine
Inovio is a public company with its headquarters in Pennsylvania, USA. Inovio and CEPI had an existing agreement to develop non-COVID-19 vaccines. An initial investment of $9m was made under a new agreement to fund the phase 1 clinical trial of the COVID-19 vaccine. The nucleic acid vaccine requires a device for delivery and funding of $5m was provided to develop the device. A further $8m was provided in support of manufacturing work. CEPI’s funding ends upon completion of the phase 1 trial.
Where will the vaccine be made? USA
How much vaccine will be supplied to the COVAX Facility? Inovio agreed to develop an appropriate Equitable Access Plan with CEPI which may include offering doses to the COVAX Facility both during the pandemic and after the pandemic.
How will be the Price be determined? The agreement defines Equitable Access as meaning that appropriate products are first available to populations when and where they are needed and at prices that are affordable to the populations at risk, especially Low-income and Middle-income Countries, or to public sector entities that procure on their behalf. Thus, Inovio has agreed contractually with CEPI’s equitable access principles.
How will results support the research community? Inovio has agreed to abide by the guidance on access to data and open publications provided by WHO and Wellcome, and additional CEPI obligations in the agreement.
Enabling Equitable Access to COVID-19
Vaccines:
Summary of equitable access provisions in CEPI’s COVID-19 vaccine development agreements
V1.0, 17 December 2020
https://cepi.net/wp-content/uploads/2020/12/Enabling-equitable-access-to-COVID19-vaccines-v1-17Dec2020.pdf
Funding and Access to Development Tools. CEPI’s enabling science program provides the tools and knowledge for developers all over the world, including those in LMICs, to accelerate their programs and make smarter development decisions. This work involves developingstandardizedassays,developinganimalmodelsandenablingaccesstothem, and creating a centralized laboratory infrastructure for sample testing. The importance of not just developing but also standardizing these vaccine development tools and resources to guide development and regulatory approval cannot be underestimated. CEPI’s enabling scienceprogramisdesignedtobenefitvaccinedevelopersthroughouttheworld,including those which are not part of the CEPI COVID-19 portfolio.
Target Product Profile. The ability to deliver a vaccine in a pandemic setting will be critical to the success of vaccination programs. Several leading candidates will be challenging to deployforcountrieswithlimitedinfrastructureduetofactorslikecostandstorage requirements at very low temperatures. Therefore, CEPI is considering factors such as storage conditions, method and route of administration, cost of goods, and number of doses required when making initial investment decisions as well at stage gate reviews.
Clinical & Regulatory. CEPI engages in the clinical and regulatory aspects of COVID -19 vaccine development at both the project level and also within the broader environment of regulatoryauthorities.NoregulatoryauthorityhasexperiencewithlicensingCOVID-19 vaccines, and few have experience with licensing vaccines in pandemic settings.
As a project level example, CEPI has made its service provider, the Safety Platform for Emergency vaccines (SPEAC) Project (of the Task Force for Global Health), available to developers to enhance their regulatory strategy and submissions to licensing agencies as wellastoobtainanoverallsafetydatabaseforclinicaltrials.
To accelerate access to vaccines in LMICs, COVAX facilitates interaction between regulatory agencies, e.g. African Vaccine Regulatory Forum, European Medicines Agency, US Food and Drug administration, to discuss regulatory approaches for vaccines against COVID-19.Thereisanurgentneedforcollaborationbetweenregulatoryauthoritiesin developing an internationally harmonised approach to regulatory review of COVID -19 vaccines. This includes review of clinical trial applications, release of clinical trial material, safety and efficacy review, genetically modified organism (GMO)-classification and timely good manufacturing practices (GMP)-inspections and post-licensure commitments. This is a particularly critical element to avoid delayed authorization and hence enable timely access in developing countries with less mature regulatory agencies and procedures.
Manufacturing. A unique challenge for the COVID-19 pandemic is the need to invest in manufacturing of hundreds of millions of doses of vaccine before having the vaccine development data a developer would usually have to guide those major investments. There are also challenges with gaining access to the raw materials needed to produce those large quantities of vaccines. There is a significant risk to global equitable access posed by some countries taking steps to protect their populations by directly securing supplies of vaccines. Accordingly, CEPI is making investments in manufacturing capacity for some of thedevelopersitsupportsinparalleltotheirearlystagevaccinedevelopmentactivities.
Some COVID-19 vaccine developers have already planned for manufacturing and have access to the necessary expertise and facilities. In other cases, CEPI is making investments toprovidemanufacturingcapacitytoscale-upthedeveloper’sexistingcapacity.CEPIis also investing in manufacturing capacity to scale-out (expand production in other countries) to diversify locations of vaccine production to mitigate the risks of vaccine nationalismasthecompetitionfordosesisfierce.CEPIcollaborateswithdevelopersinthe selection of the additional manufacturers to enable sufficient manufacturing capacity and equitableaccess.Developersagreetotechnologytransfertotrustedpartners,and/or standing up manufacturing capacity in two or more jurisdictions, if applicable.
Jointly agreeing with developers, the sites for manufacturing and conditions under which CEPI will finance that work have been areas of major focus and negotiation. The Secretariat has focused on funding or shared-risk financing for increased production capacity in geographically dispersed manufacturing locations in return for a supply of doses to the COVAX Facility.
Competition for vaccine-related supplies is also fierce, particularly for the glass vials required to store vaccines. In response, the Secretariat has purchased 100 million 20-dose glass vials6 for use by CEPI’s developers and lent funds to developers to pay to reserve or procure items in short supply from manufacturing capacity to raw materials.
Through CEPI’s sustainable manufacturing program, the Secretariat has also undertaken matchmaking between developers and certain Contract Development and Manufacturing Organizations (CDMOs) for available manufacturing capacity. A significant hedge against the diversion of doses from the COVAX Facility may ultimately be where the doses are produced.
Special requirements have been included in CEPI’s evolving vaccine development agreements that focus on manufacturing. Especially important have been efforts to manufacture large amounts of vaccines in parallel to safety and efficacy trials. In other words, CEPI is making investments, at risk, in order to produce vaccines much sooner than would normally be the case through traditional vaccine development approaches. If the
vaccine is successful, then the people who need the vaccines will not lose time waiting for the manufacturing process to be organized and implemented.
If a developer cannot use the CDMO manufacturing capacity reserved using CEPI funds, that capacity can be used as directed by CEPI for other vaccines. Termination for breach of contract or key development failures are included in CEPI vaccine development agreements, although it should be noted that given the degree to which activities are running in parallel even with early termination most of the investment would not be returned.
Supply of doses. The overarching principle in the CEPI partnering agreements is that all manufacturingoutputcorrespondingtotheCEPI-fundedpartofdevelopmentaretobe offered first to the COVAX Facility.
As part of COVAX, CEPI’s primary focus is accelerating the development of safe and effective vaccines and establishing sufficient manufacturing capacity to enable billions of doses of vaccine to be supplied.
Since Gavi will directly negotiate price and supply with developers, the Secretariat is working with Gavi to enable a smooth transition as part of the end-to-end coverage that is necessary to move quickly.
Agreement terms on supply cover the amount to be supplied globally during the “pandemic period,” which is the time from when WHO declared a public health emergency of international concern (PHEIC) for COVID-19 and when they declare that it is over. Each agreement, where applicable, also agrees to the supply of a portion of vaccine production that will be available to LMICs (or to a purchasing agent on their behalf) in the “post- pandemic period.”
Lastly, the Secretariat is participating in a COVAX working group to develop approaches to address indemnification and liability, including a compensation scheme. The presence of such legal provisions will be a prerequisite for industry partners to deliver vaccines under the COVAX Facility, and for distribution and deployment of vaccines in any country.
Pricing. CEPI has sought to enable low pricing both by requiring developers to enter into procurement deals with Gavi for the COVAX Facility, and sharing the risk of inventory build. Where CEPI’s agreements require developers to enter into such procurement deals, the price will be determined in negotiations between the developer and Gavi on behalf of the COVAX Facility, consistent with the developer’s commitment to CEPI’s equitable access policy. If the COVAX Facility is not funded or does not enter into purchase agreements as anticipated, CEPI has the right to redirect the supply to another public sector procurer. All of the agreements require compliance with CEPI’s equitable access policy and/or contain similar commitments in principle, including pricing at levels that are affordable to the people who need the vaccines. Where appropriate, commercial benefits sharing is crystallised in a form most useful in the pandemic, including dose or price commitments. Several companies have declared publicly that they will sell vaccine at “no-profit, no-loss” pricing during the pandemic period.
Canada to contribute $485M to help developing countries cope with COVID-19
Canada is providing $485 million to help developing countries cope with COVID-19, including therapies to limit deaths and ease the burden on strained health-care systems.
International Development Minister Karina Gould and Public Services and Procurement Minister Anita Anand announced the funding during a news conference in Ottawa today.
"The faster we can get tests, treatments and vaccines out to people, the sooner this pandemic can be contained. Canada's support of global efforts to find successful medical solutions is a win for all," Gould said in a prepared statement.
In the funding announced today, $230 million will target the procurement of treatments, allowing UNICEF to buy three million courses of COVID-19 antibody therapeutics after clinical trials and regulatory approvals are completed.
The other $255 million will go to Access to COVID-19 Tools (ACT) Accelerator, a coalition of international organizations and countries that is overseeing the development, production and equitable distribution of affordable COVID-19 vaccines, therapeutics and diagnostics.
Today's announcement brings Canada's total contribution to ACT Accelerator to $865 million.
Canada's contribution could also help train front-line health-care workers to administer COVID-19 vaccines and therapeutics, to plan and execute mass vaccination campaigns and to procure supplies essential to the rollout of COVID-19 vaccines and treatments, such as syringes or personal protective equipment.
https://www.google.com/amp/s/www.cbc.ca/amp/1.5840273
With-Pfizer-and-Moderna-making-headlines, learn-about-vaccine-‘cousin’-undergoing-clinical-trial in metro
by: Regan Porter
Posted: Dec 17, 2020 / 05:22 PM CST / Updated: Dec 17, 2020 / 05:24 PM CST
SHAWNEE, Kan. — A red rash at the injection site is the only side effect Brandon Kenig had to show immediately after getting the COVID-19 vaccine.
“That eventually went away,” Kenig said.
In June, he had two trial vaccine inoculations followed by several appointments for testing.
Six months later, “No effects whatsoever,” Kenig said.
Forty people were initially injected with Inovio Pharmaceuticals’ vaccine to make sure it’s safe for others to fight COVID-19. There are clinical trials in 17 cities across the country, including Kansas City. Kenig is from Shawnee.
Only a handful of people reported the rash and Kenig said that’s been the extent of his symptoms since then.
“No fever, no soreness, no headache,” Kenig said. “I know others within my trial have said that they’ve had headache, mild nausea afterwards, but I didn’t really have that at all.”
Dr. Joseph Kim said Inovio’s vaccine is DNA based, not RNA, like the ones produced by Pfizer and Moderna.
“Many of the other advanced candidates have a lot more moderate and severe cases,” Kim said.
He said they’re similar, but different, like cousins.
“RNA is not that stable; that’s why you have to keep them frozen throughout the storage and distribution,” Kim said. “In contrast, DNA vaccines are extremely stable.”
Kim said Inovio’s vaccine can be stored at room temperature, stable for one year. Then stable in a refrigerator up to five years.
“It’s a good reminding that beyond the Moderna and Pfizer vaccines that there are other vaccines in the pipeline,” Kenig said.
As someone who’s seen the process first-hand, Kenig wants Americans to have confidence in FDA-approved vaccines.
“I can personally testify to the safety and efficacy and belay any anxiety or concerns Americans may have about taking a vaccine then it will all be worth it,” Kenig said.
Inovio is in Phase Two — going from 120 to 400 clinical trial volunteers. Also adding a placebo group in the mix.
Kim hopes the vaccine will be approved and out to the public by this time next year.
Inovio is still looking for volunteers, like Kenig, to participate in the phase two of the clinical trial.
If you’re interested, visit its website at inovioDoTcom/contact-us/
fox4kcDoTcom/news/with-pfizer-and-moderna-making-headlines-learn-about-vaccine-cousin-undergoing-clinical-trial-in-metro/
12/8 Nature biomedical engineering: 10 or 100 µg of mRNA-1273. NHP challenge: no CD8+ T-cell responses
Pardi, N., Weissman, D. Development of vaccines and antivirals for combating viral pandemics. Nat Biomed Eng 4, 1128–1133 (2020). https://doi.org/10.1038/s41551-020-00658-w
Published
08 December 2020
Issue Date
December 2020
DOI
https://doi.org/10.1038/s41551-020-00658-w
When tested in rhesus macaques, two immunizations with 10 or 100 µg of mRNA-1273 induced T-helper-1-biased CD4+ T-cell responses and neutralizing antibody responses in a dose-dependent manner27. Interestingly, no CD8+ T-cell responses could be measured in vaccinated non-human primates, but the mRNA-1273 vaccine could induce a high level of protection (particularly in the high-dose group) from viral replication in the upper and lower respiratory tracts.
There are a few clinical reports of the safety and efficacy of mRNA-based SARS-CoV-2 vaccine candidates tested in a small number of people29,30. In a study of Moderna’s mRNA-1273 vaccine29, 45 (mainly white) volunteers aged 18–55 received two intramuscular immunizations of 25, 100 or 250 µg mRNA–LNPs 4 weeks apart. The results are promising, as the median magnitude of neutralizing antibody responses measured in the vaccinees was in the upper quartile of values in convalescent serum samples, and antibody titres correlated with the vaccine dose. In general, the vaccine was well tolerated, although over half of the participants receiving the 100 and 250 µg doses reported fever and other adverse events (including fatigue, chills, headache, or pain at the injection site) after administration of the second dose. Vaccine evaluation in a phase 3 clinical trial (NCT04470427) will be necessary to confirm these results and to provide more detailed comparative data on vaccine safety and efficacy in different age and ethnic groups. The nucleoside-modified mRNA–LNP vaccine developed by Pfizer/BioNTech30, which encodes a trimeric form of the receptor-binding domain of the SARS-CoV-2 spike protein, has also been tested in human volunteers. Forty-five (mainly white) individuals aged 19–54 received two intramuscular immunizations of 10 or 30 µg mRNA–LNPs 3 weeks apart, or a single dose of 100 µg mRNA–LNPs. The safety and immunogenicity results were similar to those of the Moderna vaccine, with dose-dependent neutralizing antibody titres and mild or moderate adverse events. The booster immunizations elicited significantly stronger neutralizing antibody responses. Of note, using lower vaccine doses (10–30 µg) to achieve protection from viral infection can be a critical advantage when millions or even billions of doses of a vaccine need to be rapidly manufactured. Similar to the Moderna vaccine, a larger study (NCT04368728) will shed light on the potential differences in safety and efficacy between different ethnicities and age groups.
https://www.nature.com/articles/s41551-020-00658-w
Looking for an edge in vaccines, Thermo Fisher plots major expansions across global manufacturing sites in its portfolio
December 11, 2020 10:17 AM EST
In a big year for contract manufacturers, Massachusetts’ Thermo Fisher Scientific has emerged as a leading partner for drugmakers fighting the Covid-19 pandemic, particularly in diagnostics and therapeutics. Now, buoyed by that success and looking to scale up its vaccine offerings, Thermo Fisher is plotting big expansion across its global portfolio.
Thermo Fisher will expand its facilities in Greenville, NC; Ferentino and Monza, Italy; and Swindon, England, to expand its range of offerings for customers”whether it’s an emerging biotech working on a vaccine for a novel virus or a high-volume pharmaceutical manufacturer delivering necessary medicines at scale,” a spokesperson told Endpoints News.
Thermo is keeping the capital outlay for the projects under wraps, but here’s more about each site’s expansion:
Greenville, NC: A new, standalone 130,000-square-foot building which comprises two live-virus filling lines (operational in 2022), and seven other new lines including commercial-scale liquid filling lines and a development line for liquid and lyophilized drug products and syringes (operational in 2021).
Ferentino, Italy: A 28,000-square-foot development building will offer new capacity for one flexible line of development projects and small-scale commercial manufacturing (operational in 2022), with the space to add future capabilities. The site will also add on a new high-capacity commercial liquid filling line that will be operational in 2021.
Monza, Italy: This site will expand its sterile fill-finish line capacity, with three new lines expected to be operational in 2021, including one high-capacity line for liquid and lyophilized filling, one pre-filled syringe/pre-filled cartridge line for medium batch production and one flexible multi-purpose line for low volume filling of vials, pre-filled syringes and pre-filled cartridges in nest and tub configurations.
Swindon, England: The Swindon expansion will actually revamp the existing 30,000-square-foot site into a new, full-scale commercial manufacturing facility, the spokesperson said. The site, which will be operational in 2021, will add one production line for liquid and one line for lyophilized — in addition to “extensive” cold-chain storage for vaccines that require ultra-low temperatures.
The expansions make clear the ever-growing need for viable and sterile vaccine production, even outside of the current breakneck efforts to produce a Covid-19 vaccine. Thermo Fisher has waded into that race as well, agreeing in September to produce Inovio’s Covid-19 vaccine (INO-4800) beginning in 2021.
Also on the Covid-19 front, Thermo Fisher in May entered into a deal with California-based Humanigen to help scale up manufacturing of the biotech’s lenlizumab, a clinical-stage candidate for cytokine storms that the company is testing in patients with more severe cases of the respiratory virus. In September, Thermo Fisher agreed to a deal with the US government to produce the viral transport media tubes needed to transport Covid-19 test samples.
Prior to the four expansion sites announced this week, the company also announced recently an expansion in Singapore that includes a high-speed sterile line for live-virus filling. Thermo Fisher also agreed to a joint venture with Innoforce to build a new pharmaceutical services facility in Hangzhou, China that focuses on integrated biologics drug substance and sterile drug product development and manufacturing.
Both of those sites are expected to be completed in 2022.
https://endpts.com/looking-for-an-edge-in-vaccines-thermo-fisher-plots-major-expansions-across-global-manufacturing-sites-in-its-portfolio/
KB: INOVIO's Phase 2 vaccine clinical trials underway
By: Mimi Elkalla
Posted at 5:48 PM, Dec 16, 2020 and last updated 5:48 PM, Dec 16, 2020
SAN DIEGO (KGTV) - Like Pfizer, Moderna, AstraZeneca, and many others, INOVIO Pharmaceuticals has also raced to develop a COVID-19 vaccine this year.
“We’ve been working really hard to move our vaccine through the stages of clinical testing. Some things have taken a little bit longer than we hoped. I think that’s kind of always the case when you’re trying to go at great light speed,” said Dr. Kate Broderick, INOVIO Pharmaceuticals Senior VP of Research & Development based in San Diego.
Broderick said with funding from the U.S. Department of Defense, the biotech company started its Phase 2 clinical trial evaluating its DNA vaccine candidate, INO-4800.
The first U.S. participants received a dose of the experimental vaccine earlier this month. Approximately 400 adults in the U.S. are expected to be enrolled in the trial by the end of the month.
“We hope that in the early part of 2021, we’ll be going into a really large Phase 3 trial where we’re asking the question does our vaccine protect against the disease itself,” she said.
Broderick said the company hopes to enroll about 6,000 participants initially in its Phase 3 trial once they get the green light to begin.
A press release from the company last week stated that “The Phase 3 segment of the INNOVATE remains on partial clinical hold until INOVIO satisfactorily resolves the FDA’s remaining questions related to the CELLECTRA 2000 device that will be used to deliver INO-4800 into the cells of the skin.”
Earlier data released from Pfizer and Moderna’s studies showing high vaccine efficacy was positive news for INOVIO.
“We feel that we’re in a really good place. There’s eight billion people on the planet, and we’re certainly going to need quite a few different types of vaccines to ensure everybody is protected,” she said. “The Moderna and Pfizer vaccines are RNA vaccines; ours is DNA vaccine”
Broderick said one significant benefit of INOVIO’S DNA vaccine candidate is it doesn’t have to be stored in low-temperature freezers, making it easier to ship out worldwide if approved.
“In fact, we can keep it at room temperature, sitting on a desk somewhere for a year with no impact,” she said.
INOVIO is projecting to have 100 million doses of its vaccine ready in 2021.
“With these vaccines being approved, there is definitely an end in sight, but don’t let your guard down too fast,” she said. “Unfortunately, until everyone in the country gets vaccinated, we will still have to adhere to those kinds of annoying things, wearing masks, socially distancing. I know it’s frustrating, especially before the holidays, but just keep yourself safe and the people you love safe.”
https://www.10news.com/news/local-news/inovios-phase-2-vaccine-clinical-trials-underway
Evaluate the immunogenicity and protective efficacy of pGX9501 (INO-4800) in the Rhesus macaque model of SARS-CoV-2 challenge
Texas Biomedical Research Institute
Principal Investigator(s) Carrion, Ricardo
Research Start Date
12/01/2020
StatusActive
The purpose of this study will be to evaluate the immunogenicity and protective efficacy of pGX9501 (INO-4800) at a 0.5mg and 1 mg dose in the Rhesus macaque model of SARS-CoV-2 challenge.
https://sabioscience.org/projects/evaluate-immunogenicity-and-protective-efficacy-pgx9501-ino-4800-rhesus-macaque-model-sars
Inovio to develop COVID-19 DNA-encoded monoclonal antibodies
By The Science Advisory Board staff writers
December 15, 2020 -- Inovio, along with a team of scientists from the Wistar Institute, AstraZeneca, the University of Pennsylvania, and Indiana University, has received a $37.6 million grant from the Defense Advanced Research Projects Agency, a branch of the U.S. Department of Defense, to develop COVID-19 treatments.
The grant is for the use of Inovio's DNA-encoded monoclonal antibody (dMAb) technology to develop anti-SARS-CoV-2-specific dMAbs, which could function as both a therapeutic and preventive treatment for COVID-19.
The public-private partnership means Inovio can not only broaden the scope and application of its DNA medicines, but also open the door for better patient administration and more cost-effective, scalable production of monoclonal antibody products for other infectious diseases and cancers, the firm said.
Under the two-year grant, Inovio and Wistar will construct COVID-19 dMAb candidates mirroring AstraZeneca's traditional recombinant monoclonal antibody candidates that are currently being tested in clinical trials. The dMAb candidates can be developed and produced in vivo, which offers a cost-effective and scalable therapeutic option, the firm said.
Afterward, the dMAb candidates will be advanced into preclinical studies and then into first-in-human clinical trials within one year of funding.
Monoclonal antibodies: A Covid-19 treatment people might not know about
By Andrea Kane, CNN
Updated 10:25 AM EST, Wed December 16, 2020
CNN) There are very few drugs that prevent people with early Covid-19 from progress to severe disease, but monoclonal antibodies may be among them.
Early study results show they may reduce the rate of hospitalizations by up to 70% if they are taken in time, which can be life-saving, especially among people who are at high risk of getting very sick.
But it seems that the word is not getting out to those who need the medications the most, or their health care providers.
Eli Lilly's monoclonal antibody, called bamlanivimab, received an emergency use authorization from the US Food and Drug Administration in early November. Less than two weeks later, the agency granted an EUA to Regeneron's monoclonal antibody cocktail, made up of two monoclonal antibodies, casirivimab and imdevimab, and called REGEN-COV2. It was given to President Trump when he got infected at the start of October. Former New Jersey Gov. Chris Christie and Housing and Urban Development Secretary Ben Carson were also treated with monoclonal antibody therapy.
According to the FDA, monoclonal antibodies should be given as soon as possible after symptoms emerge and a person tests positive for infection. And, because of limited supply, the authorizations are limited to high-risk patients, such as people 65 and older, those who have a BMI (body mass index) of 35 or greater and those with other health conditions like diabetes, cardiovascular disease or chronic kidney disease.
"The monoclonal antibodies we've authorized seem to work best for preventing hospitalization in outpatients early in their disease -- typically within 10 days of the onset of symptoms, if you are a high-risk individual. So, over the age of 65, or over the age of 55 with a comorbidity, or... some preexisting illness to put you at risk," FDA Commissioner Dr. Stephen Hahn told CNN's Dr. Sanjay Gupta in mid-December.
"These antibodies, for the last month since authorization, have been distributed around the country. So, they should be available locally, and it's under state jurisdiction," Hahn said.
At a time when hospitals across the country are running out of beds and staff to care for the severely ill, monoclonal antibodies may have a real role to play. So why aren't more people trying to access these potentially life-saving medications, especially since both the drugs are mostly free, under Operation Warp Speed?
"We've got to get the therapeutics used. We need patients who test positive, who are at risk of hospitalization, to get on these monoclonal antibodies. We actually have more right now than there are getting used. We've got to get them earlier, so we keep people out of hospitals," Health and Human Services Secretary Alex Azar told CNN's Jake Tapper Monday.
An HHS spokesperson confirmed that a new report showed only 5%-20% of the available supply of monoclonal antibodies are actually being used -- an ironic statistic considering one big concern was that there would not be enough supply to meet demand. It is the first time HHS had requested utilization information from facilities and providers administering the drugs.
"We will continue working with stakeholders to learn more about drug utilization decisions," the spokesperson said.
How monoclonal antibodies work
To fight infections, the immune system produces different types of antibodies that target different parts of the invader, explained Gigi Kwik Gronvall, senior scholar at the Johns Hopkins Center for Health Security.
"When you have an infection, your immune system kicks into action and you produce antibodies," Gronvall said.
"The best antibodies stick to the pathogen -- in this case, it will stick to the virus and prevent the virus from infecting your cells. So, antibodies have a real role in stopping infections."
That's why convalescent plasma therapy is sometimes used to treat patients infected with coronavirus. It involves taking the antibody-containing plasma from someone who has recovered from Covid-19 and infusing it into a sick person in the hopes of kickstarting their immune response. But some antibodies work better than others and different people have different levels of antibodies, so results from convalescent plasma aren't always uniform.
Monoclonal antibodies to treat coronavirus Covid-19 are intensely focused, lab-made versions of convalescent plasma. Scientists looked for the antibodies that best blocked infection by the SARS-CoV-2 virus. "They picked a particular kind of antibody -- what they call a neutralizing antibody... and made a purified version of it to be used as a medicine," Gronvall said.
Eli Lilly's drug uses one particular antibody and Regeneron's drug uses a combination of two others. Early study results have shown they appear to reduce the changes of winding up in a hospital or the emergency room by between 55% and 70%.
Neither medication is fully FDA-approved and not everyone is convinced the evidence so far is strong enough to support routine use. The National Institutes of Health's Covid-19 treatment guidelines, for example, say "there are insufficient data to recommend either for or against the use" of either product "for the treatment of outpatients with mild to moderate Covid-19."
Similarly, a guideline panel for the Infectious Diseases Society of America "suggests against routine use of bamlanivimab for ambulatory patients with Covid-19." However, the panel noted that some people at increased risk of progressing to severe Covid-19 "may reasonably select this treatment after careful discussion with their clinician."
It's important also to note that monoclonal antibodies don't appear to help -- and may actually harm -- people who are hospitalized. Both Lilly and Regeneron ended trials of their drugs in severely sick patients.
Limited supply?
Azar told reporters at an Operation Warp Speed briefing in mid-December that more than 278,000 courses of the two antibody treatments have gone out to medical facilities, and that the administration is working to send out more.
The government initially bought 300,000 doses of bamlanivimab and in early December bought an additional 650,000 doses, according to an Eli Lilly statemen, which also says it "continues to manufacture bamlanivimab for use around the world, and the supply is expected to increase substantially in 2021."
A release from Regeneron notes it "expects to have treatment doses ready for approximately 80,000 patients by the end of November, approximately 200,000 patients by the first week of January, and approximately 300,000 patients in total by the end of January 2021."
While that may sound like a lot of doses in total, they come at a time when new coronavirus cases in the United States alone are averaging more than 215,000 per day -- although it's important to note that not everyone who is infected has risk factors for developing severe disease and so may not be a candidate for one of these medications.
Both companies told CNN in separate emails that supply is expected to increase in 2021 as additional manufacturing resources "scale up" (Regeneron) and "come online" (Eli Lilly).
In addition to Lilly and Regeneron's monoclonal antibody medications, there are more than 70 different antibody treatments for Covid-19 under investigation, according to BIO, an association that represents major biotechnology companies.
Other hurdles
There are several reasons why monoclonal antibodies are in scarce supply. For one, unlike most drugs, which are made by combining specific chemical ingredients following a precise process, monoclonal antibodies are very large and complex molecules that are complicated to produce. That's because they're what's known as a biologic: biologics are manufactured in a living system such as a microorganism, or plant or animal cells.
"It's not like aspirin or just, you know, when you're making a chemical [drug]; these are biologics and it takes a lot of work to make them, purify them and put them in a form for delivery. So there are lots of steps along the way," says Gronvall.
According to Fouad Atouf, the vice president of global biologics at US Pharmacopeia, the nonprofit organization that sets quality standards for medicines and related products, purification is "very laborious."
"But there is, thanks to the advances in science, specifically the recombinant-DNA technology approach, where you can use cell lines as factories. And now you can create synthetic copies of those antibodies," he said. In other words, cells can be genetically engineered and turned into factories for churning out monoclonal antibodies.
Because of this, according to Atouf, manufacturing capacity is limited. "You can only make fewer doses at a given time."
Another issue, he said, is sheer volume: you need to give a patient a lot more of a monoclonal antibody than, say, a vaccine or a pill.
A third issue, the one that worries him "a lot" the competition for the raw ingredients.
Despite the challenges, Atouf said monoclonal antibodies have a lot of potential. In addition to treating people with mild Covid-19, he said there are studies looking to see if they can be given prophylactically, to prevent an infection; there's also research looking into whether they can be used against existing and emerging coronaviruses.
Access to a monoclonal antibody
There are a couple of additional hurdles that need to be overcome to get monoclonal antibodies to people in time to help. One is to decide where the limited supply of medications get shipped to.
To make access as fair as possible, the medications are allocated weekly to each state by the government, under Operation Warp Speed, based on confirmed Covid-19 cases in that state during the previous seven days. The individual state health departments are then responsible for deciding how many doses to send to which health care facilities in their state. AmerisourceBergen, a national distributor, will deliver the allotted medications directly to the health care facilities overnight.
Another challenge with monoclonal antibodies is that they are not easy to administer, requiring a one-hour IV infusion and an hour observation period in an outpatient setting. So, any location that's going to administer these medications must be set up to keep Covid-19 patients isolated from their other patients during the two-hour infusion and monitoring process.
The FDA's Dr. Janet Woodcock, the head of the Center for Drug Evaluation and Research and an Operation Warp Speed leader, suggested during a news conference in early November that pop-up infusion centers may be one solution.
Another solution may be partnering with pharmacy chains. HHS recently tapped CVS's infusion care business, Coram, for a pilot program to administer 1,000 doses of bamlanivimab to qualified patients both at home and in long-term care facilities. The program launched on December 3 in seven cities and their surrounding communities, including Boston, Chicago, Cleveland, Los Angeles, Milwaukee, Minneapolis and Tampa.
Patient awareness also needs to be raised. "We're all going to need to get the word out that people with high risk have therapeutic option now, as outpatients. Up until this point, people been told to stay home unless they get very sick," said Woodcock.
Steve Rudner, the director of pharmacy network contracting at Vizient, a health care performance improvement company, agrees. "Like with many pharmaceutical agents or drugs, the patient might not know if they are in fact, a candidate for this," he said.
"If you're a health care provider and you just confirmed a case of Covid with a patient, and they fall into one of the high-risk categories ... it's your mission to make sure that that patient understands, 'Here is a one-hour infusion that could prevent you from going in the hospital,'" he said.
But there's a role for patients too, said Rudner. "If a patient reads [an] article and says, 'Wait a second: maybe I'm in one of these high-risk categories. If my physician doesn't ask me about it, maybe I should ask him or her about it because I just I just tested positive and I don't want to go into hospital,'" he said.
The FDA's Hahn echoed the sentiment. "I would encourage anyone who might be in the categories I described to talk to their provider about this, because as an outpatient, these can be infused to those folks who are in high-risk populations. We know that the clinical endpoint is prevention of hospitalization," Hahn said.
"God knows the health care systems are significantly overstressed at this point, so I would encourage your viewers to ask the providers about this."
Alaska-Health-Worker-Had-a-Serious-Allergic-Reaction-After Pfizer’s Vaccine
The person did not have a history of drug allergies. Two similar reactions happened last week in Britain.
Vaccines being prepared in Fargo, N.D., on Monday. The reaction was believed to be similar to the reactions two health workers in the U.K. experienced after receiving the Pfizer vaccine last week. They both recovered.Credit...Tim Gruber for The New York Times
By Noah Weiland, Sharon LaFraniere and Katie Thomas
Dec. 16, 2020
Updated 1:21 p.m. ET
WASHINGTON — A health worker in Alaska had a serious allergic reaction after getting Pfizer’s coronavirus vaccine on Tuesday and was hospitalized, according to three people familiar with official reports of the person’s health. The person was still in the hospital on Wednesday morning, under observation.
Government officials were scrambling on Wednesday to learn more about the case. The worker had no history of drug allergies but it was unclear whether he or she suffered from other types of allergies, according to one person familiar with the case.
https://www.nytimes.com/2020/12/16/health/covid-pfizer-vaccine-allergic-reaction.html