Life long Maverick: Seen it ALLl in 40 yrs of PROF. exposure as invest analyst/port mgr on the FRONT lines vs iHub Msg Bds.
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Inflammation-Driven Deterioration Of Structural Proteins Contributes To Aging
How to reduce inflammation
It's the secret to ageing well...
Inflammation: Prime Cancer Cause 3/2019 Cancer Research UK
Better Treatments Needed to Boost Brain Cancer Survival: Study
brain scans
FRIDAY, June 21, 2019 (HealthDay News) -- Glioblastoma brain cancer remains one of deadliest tumors, and new research shows five-year survival rates remain low for patients with the disease.
While there have been improvements in short- and medium-term survival rates for patients with the most common type of brain tumor in adults, only 6% of patients live for five years after diagnosis, according to the Mayo Clinic researchers.
Glioblastomas claimed the lives of both Sen. Ted Kennedy in 2009 and his colleague in the senate, John McCain, who succumbed to the cancer in 2018.
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The new study's authors believe more aggressive treatments need to be considered for all glioblastoma patients. They published their findings in July in the journal Mayo Clinic Proceedings.
the study was based on a review of nearly 49,000 glioblastoma cases in a national database from 2004 through 2009. It found that only 2,249 patients lived at least five years after diagnosis (or 4.6%).
Among those patients who lived for at least five years, the median length of survival was 7 years and 4 months.Median means half lived longer, half lived less time.
Those living longer were relatively younger adults, female and nonwhite, the study found. Other factors in five-year survival included generally good health; higher income; tumors that were on the left side of the brain or outside the brainstem; and radiation treatment.
Tumor size did not appear to have a significant effect on long-term survival, a finding at odds with previous studies.
"The introduction of chemotherapy in the treatment of glioblastoma was revolutionary, although this research suggests that chemotherapy serves more as a temporizing measure against disease recurrence and death," said study senior author Dr. Daniel Trifiletti, a radiation oncologist with the Mayo Clinic in Jacksonville, Fla.
"Considerable work needs to be done to provide hope for patients with glioblastoma," he added in a Mayo news release.
Trifiletti said that will likely require "novel and radical" approaches to treatment.
Gliomas represent about 75% of malignant primary brain tumors, according to previous studies, and glioblastoma, grade 4 glioma, is among the most aggressive forms of cancer.
Trifiletti and his co-authors said nearly all glioblastoma patients should be offered enrollment in a clinical trial. Several studies are underway to test new surgeries, radiation techniques and drug therapies.
"To me, the most exciting area is in cellular therapy," Trifiletti said. "In my lab, I am evaluating the possibility of using targeted cellular therapy as an agent that can synergize with existing therapies, including radiation."
More information
The American Brain Tumor Association has more on glioblastoma.
SOURCE: Mayo Clinic, news release, June 20, 2019
-- Robert Preidt
DIFFERENT STROKES FOR DIFFERENT FOLKS
https://www.bloomberg.com/news/articles/2019-06-20/neil-woodford-s-fall-holds-lessons-for-investors-everywhere
DIFFERENT STROKES FOR DIFFERENT FOLKS
Neil Woodford holds talks with Kent County Council over access to £263m pension investment
Evaluate: What you indicate may well be.
The words used were NOT mine:
IRANO: Immunotherapy Response Assessment in Neuro-Oncology (iRANO): A Report of the RANO Working Group
Lomustine-temozolomide combination therapy versus standard temozolomide therapy in patients with newly diagnosed glioblastoma with methylated MGMT promoter (CeTeG/NOA–09): a randomised, open-label, phase 3 trial
Study shows that glioblastoma patients survive significantly longer with combination chemotherapy
by University of Bonn Feb 2019
Prof. Dr. Ulrich Herrlinger and Dr. Christina Schaub with pictures of a glioblastoma patient after combination therapy. Credit: Katharina Wislsperger/Kommunikation und Medien des UKB
Cancer researchers at the University of Bonn have reported significant progress in the treatment of glioblastoma. About one third of all patients suffer from a particular variant of this most common and aggressive brain tumor. Survival of these patients treated with the new combination therapy increased on average by nearly half compared to patients who received the standard therapy. The study has now been published in the journal The Lancet.
In Germany, around 2,400 people are diagnosed with glioblastoma every year. Most of those affected are adults between the ages of 50 and 70. Following radiation therapy, patients currently receive chemotherapy with the substance temozolomide (TMZ). This is considered the most effective weapon against glioblastoma. The drug alters the DNA in the cancer cells, which die as a result. This stops the growth of the tumor for some time. However, the disease is not yet curable.
Temozolomide is particularly effective in treating a subform of glioblastoma. In this subform, a genetic sequence in the cancer cells, the so-called MGMT promoter, is chemically altered. Experts call this an MGMT promoter methylation. It causes the MGMT gene that is controlled by the promoter to be read less frequently. This allows temozolomide to attack the tumor better. However, its effect is limited, even in this patient group. Attempts were therefore made to combine the drug with other drugs in order to achieve better results—for a long time without success.
Well-tolerated side effects
A pilot study conducted several years ago gave rise to new hope. Scientists led by Prof. Dr. Ulrich Herrlinger (Department of Neurology and Center for Integrated Oncology (CIO), University Hospital Bonn) administered temozolomide together with CCNU, another cancer drug that has an effect on the DNA. "At the time, we found first indications that this combination might be able to significantly improve the prognosis," explains Herrlinger. "In order to confirm these results, we started a large patient trial with funding from the Federal Ministry of Education and Research. We have now been able to show that the administration of CCNU and TMZ actually significantly prolongs the survival time of our patients, and that with well-tolerated side effects."
A total of 17 centers in Germany with almost 130 patients were involved in the study that has now been published. On average, the patients receiving this kind of treatment survived about four years, more than 16 months longer than with TMZ alone. "This is a major success," says Herrlinger. "Since the initial approval of temozolomide in 2005, chemotherapy of glioblastoma had made virtually no progress." The researchers are now trying to further improve the therapy, for example by combining three drugs.
However, only patients with a methylated MGMT promoter benefit from the new treatment approach—just over one third of all patients. "This is a tailor-made therapy for this subgroup," says Herrlinger. "Ultimately, this is an initial step toward personalized cancer medicine for glioblastoma patients." The Neurooncology Center of the University Hospital Bonn now offers these patients the CCNU/TMZ combination also outside of clinical studies.
Explore further
MGMT promoter methylation associated with improved survival for patients with WHO Grade II Gliomas
More information: Ulrich Herrlinger et al. Lomustine-temozolomide combination therapy versus standard temozolomide therapy in patients with newly diagnosed glioblastoma with methylated MGMT promoter (CeTeG/NOA–09): a randomised, open-label, phase 3 trial, The Lancet (2019). DOI: 10.1016/S0140-6736(18)31791-4
Journal information: The Lancet
Provided by University of Bonn
Germany (Sickness Funds etc)German patients get the latest drugs for just $11. Can such a model work in the U.S.?
Patients who come to the Havelhöhe cancer clinic in the leafy outskirts of Germany’s capital are often very sick.
Struggling with advanced-stage cancers, many need strong doses of expensive, cutting-edge chemotherapy that can run into the hundreds of thousands of dollars.
But like all Germans, none of the patients sitting quietly in the infusion ward here pay more than 10 euros a prescription, or about $11. “We never talk about costs,” said Dr. Burkhard Matthes, a senior oncologist at the clinic.
Germany’s ability to provide citizens access to the latest drugs while keeping patients’ costs so low is made possible by a novel strategy launched in 2011 to rein in exploding prices that were threatening to bankrupt the nation’s healthcare system.
Mixing free-market incentives to encourage innovation with regulation and lots of transparency, Germany’s drug review process gives manufacturers the chance to bring new products to market and charge higher prices — but only if they can show the new medications are better than existing ones.
Nearly the entire process is open to the public, giving doctors, hospitals and patients access to not only new drugs, but also independent evaluations of how well they work.
And it’s kept drugs accessible. Just 7% of Germans reported cost-related problems getting medical care in the last year, compared to a third of Americans, an international survey found.
“There is a lot we could learn,” said Leigh Purvis, who oversees prescription drug policy for the AARP and has urged U.S. policymakers to more closely study the German model.
Germany, like the U.S., relies on private health insurers and private doctors. The German government doesn’t set drug prices, as some European nations do. And the country — home to some of the world’s largest drug makers — has a robust pharmaceutical market.
“Germans don’t believe the government should run the healthcare system,” said Franz Knieps, a former senior government health official who now heads an association of large German insurers. “But they wanted a system that’s affordable.”
Building that wasn’t easy, but politicians, healthcare leaders and industry officials settled on a compromise that has saved billions of dollars and won the acceptance of even many drug makers.
“We had a lot of doubts about the system when it first started,” said Dr. Markus Frick, a senior official at Germany’s leading pharmaceutical industry group, the VfA. “Now we see it works for many, though not all, cases.”
Germany’s drug pricing initiative was born of widespread fears — not unlike those driving today’s U.S. debate — that the rising cost of new specialty drugs would make health coverage unaffordable.
With roots that date to the 19th century when industrial employers offered health protections to head off a threat of socialism, the German healthcare system is built on a tightly regulated market of private, nonprofit insurers, known as sickness funds.
Germans are required to enroll in one of these funds, which are similar to U.S. health insurers.
There are strict limits on how much patients must pay for their medical care — a major difference from the U.S., where patients’ deductibles have been soaring. Co-pays, for example, are limited to 10 euros per prescription. There are no deductibles.
Sickness funds must cover new drugs as soon as they become available.
Importantly, the funds also must collect enough in premiums to cover the costs of their members’ medical care.
That meant that when drug prices started shooting up in the 2000s, sickness funds began running deficits and faced pressure to hike premiums.
“It was a situation we couldn’t accept,” said Daniel Bahr, a former minister of health. “We needed change.”
On the left, politicians clamored for government price controls. Germany’s powerful pharmaceutical industry, in an echo of arguments made in the U.S, warned that would choke off innovation.
Chancellor Angela Merkel’s right-of-center government chose a middle path.
New drugs would have to go through a system of rigorous evaluation. Using the evaluations, sickness funds — not the government — would then negotiate prices with drug makers.
Under this new system — known by its German acronym AMNOG — sickness funds must pay drug companies the list price for new drugs for one year after they are introduced, an important feature of the system designed to ensure patient access to new therapies.
But the foundation of the system is an independent, transparent assessment of new drugs that is undertaken when the drug enters the market.
Manufacturers must submit information about new drugs to a non-governmental agency that compares them to existing therapies.
The system “asks a very basic question: Is there an added benefit from a new drug? And it’s on drug makers to prove their case,” said Dr. Jürgen Windeler, head of theInstitute for Quality and Efficiency in Health Care, or IQWiG, the agency that conducts the analysis.
In a futuristic office park just outside the historic center of Cologne in Germany’s Rhineland, teams pore over thick dossiers of clinical trial data and other information submitted by drug companies.
The teams want to see not just that a drug works, a standard applied in the U.S. The agency demands evidence that companies have tested their therapies against alternatives. And it wants proof a drug improves long-term outcomes, such as helping patients live longer.
At the end of a three-month evaluation, the agency issues a report with a formal determination of whether a drug works better than available treatments, whether it offers no new benefit or whether there is not enough evidence to quantify the benefit.
Each report and all the evidence, neatly bound in a white spiral and kept on file at the agency, is public.
After the findings are published, drug companies, physician groups, patient advocates and other stakeholders can offer public comments on the report.
If a company can’t show its drug is better than existing therapies, it can only charge as much as the comparable existing drugs in the same category.
If, on the other hand, the new drug is shown to be better, the manufacturer can negotiate a price with the sickness funds.
In another important feature of the German system, the sickness funds maximize their leverage by negotiating collectively and settling on a maximum price that all funds will pay.
That is a major difference from the U.S., where insurers and pharmacy benefit companies negotiate their own prices with drug makers, based on their own evaluations, all of which are generally secret.
“The transparency is excellent,” said Dr. Wolf-Dieter Ludwig, chairman of the German medical association. “We get more information about new drugs and we get comprehensive, independent assessments.”
The Trump administration and many in Congress are increasingly calling for more transparency in the U.S. drug market as well. And congressional Democrats want Medicare to use its leverage to negotiate lower drug prices for seniors. But thus far, there has been little progress on Capitol Hill, where drug companies continue to wield influence.
Germany also ran up against industry. Pharmaceutical companies initially chafed at providing data, Windeler said.
The assessments have also been tough. Nearly half of the 338 evaluations conducted since the system debuted have found no clear advantage over existing therapies.
Nor are sickness funds always able to settle on a price with drug companies; in about a fifth of the cases, negotiations have gone to arbitration, a legal process for setting prices.
In a few cases, companies unhappy with how their drug was graded or dissatisfied with the price have pulled out of the German market.
In 2011, for example, Boehringer Ingelheim, a leading German manufacturer, and American drug giant Eli Lilly stopped marketing the diabetes drug Trajenta in Germany.
Most companies, however, have been reluctant to abandon Europe’s largest market.
At the same time, the review process has helped restrain prices, while still getting new drugs into the market, evidence shows.
When, for example, Pfizer in 2016 introduced a new breast cancer treatment called Palbociclib, the U.S. drug maker charged 66,000 euros, or about $74,000, for an annual course of the therapy.
That was far more than existing breast cancer drugs such as Tamoxifen, which cost just 71 euros, or $79, a year in Germany, or Anastrozol, whose annual cost was 303 euros, or $339, according to the assessment.
German evaluators didn’t give Pfizer’s drug a strong recommendation, concluding that while Palbociclib appeared to slow tumor growth, the drug didn’t appear to measurably prolong patients’ lives.
Physician and patient groups nevertheless argued strongly for access to Palbociclib. And the sickness funds agreed to negotiate with Pfizer. They ultimately settled on a price of 35,000 euros a year, or $39,000, an almost 50% discount off the original price.
Although many in Germany wish the system was saving more, it is generally credited with lowering overall drug spending by about 2 billion euros a year, or about 5%. In the U.S., that would translate into more than $18 billion in annual savings.
Total German spending on retail drugs — including what sickness funds and patients pay — is still among the highest in Europe, topping $775 per person annually, according to the Organization for Economic Cooperation and Development. But that is still considerably lower than in the U.S., where per-person spending exceeds $1,200, the highest in the world.
Equally important, the system has opened the drug market to public scrutiny, a marked contrast to the secrecy that cloaks the U.S. market.
Dr. Antje Haas, who oversees price negotiations with drug makers for the national association of sickness funds, known as the GKV-Spitzenverband, called the transparency “the real jackpot.”
At the AARP, Purvis noted that it wouldn’t be necessary to replicate all of Germany’s drug pricing system to help American patients.
If Congress and the White House only devised a more uniform system for assessing the value of drugs and making that information publicly available, as it is in Germany, that would be a major step forward, she said.
Support for this story came from the Assn. of Health Care Journalists' International Health Study Fellowship, funded by the Commonwealth Fund.
The latest from Washington »
More stories from Noam N. Levey »
Some PERTINENT answers about BioNTech:
BioNTech SE is Europe’s largest privately held biopharmaceutical company pioneering the development of individualized therapies for cancer and other diseases. The Company combines all of the building blocks of individualized immunotherapy under one roof – from diagnostics and drug development to manufacturing. Its cutting-edge technologies range from individualized mRNA-based medicines through innovative chimeric antigen receptors and T-cell receptor-based products to novel checkpoint immunomodulators. BioNTech’s approach is validated by six top-tier corporate partnerships with Genentech, Genmab, Eli Lilly and Company, Sanofi, Pfizer, and Bayer Animal Health. Founded in 2008, BioNTech’s shareholders include the MIG Fonds, Salvia and the Strüngmann Family Office, with the Strüngmann Family Office as the majority shareholder. Following the seed round fundraising in 2008, the Company completed a USD 270 million series A round of financing in 2018. The Series A round was led by the Redmile Group and joined by Janus Henderson Investors, Invus, Fidelity Management & Research Company and several European family offices. BioNTech has grown rapidly to more than 1000 employees.
PIPELINE:
https://biontech.de/pipeline-patients/
Cancer-Vaccine Maker BioNTech Considering an IPO in U.S.
By Ruth David and Naomi Kresge
February 5, 2019, 12:03 PM PST Updated on February 6, 2019, 4:48 AM PST
Potential advisers have suggested a value of about $5 billion
German biotech firm competes with Massachusetts-based Moderna
https://www.bloomberg.com/news/articles/2019-02-05/cancer-vaccine-maker-biontech-is-said-to-consider-ipo-in-u-s-jrs6zoab
DIFFERENT STROKES FOR DIFFERENT FOLKS
DFFN in ndGBM Ph3: latest details here:
http://secfilings.nasdaq.com/filingFrameset.asp?FilingID=13455636&RcvdDate=5/28/2019&CoName=DIFFUSION%20PHARMACEUTICALS%20INC.&FormType=424B5&View=html
DIFFERENT STROKES FOR DIFFERENT FOLKS
Hard knocks for brain cancer, again
Vantage Logo May 22, 2019
Amy Brown
In the wake of two phase III glioblastoma failures this month, from Abbvie and Bristol-Myers Squibb, hopes dim for another big readout from Tocagen.
Glioblastoma’s intractable and aggressive nature means that few novel agents make it to late-stage testing. Two phase III blow-ups this month have left the pipeline looking particularly bare, and news from Tocagen last night suggests that another asset could be heading for the scrapheap.
A pivotal trial of the viral gene therapy Toca511/FC will continue to final readout, the company said, dashing hopes of an early stop for efficacy. There is a small chance that a survival benefit will ultimately be seen, but the recent failures, of an antibody-drug conjugate from Abbvie and Bristol-Myers Squibb’s Opdivo, show just how hard it is to make progress in this disease.
These two setbacks arguably leave five active phase III trials of novel glioblastoma agents, including Tocagen’s. There were nine ongoing studies flagged as worth tracking last year, when Vantage last looked at the space, and no new names have made it into phase III since then (Therapy focus: no giving up on brain cancer, 12 March 2018).
This amounts to a disappointing lack of progress. True, there are many agents in earlier stages of testing: EvaluatePharma counts 49 phase I or II glioblastoma assets that are considered their respective developers’ lead, but in reality a number of these have probably already been quietly abandoned, and few will make it into larger trials.
Notable phase III novel agents targeting glioblastoma multiforme
Project Mechanism Company Trial ID Notes
Opdivo Anti-PD-1 MAb Bristol-Myers Squibb NCT02617589
NCT02667587 Checkmate-498, vs Temodar: failed May 2019.
Checkmate-548, on top of Temodar: data due this year.
Depatuxizumab mafodotin Anti-EGFR ADC Abbvie NCT02573324 Intellance-1 study, on top of Temodar in patients with EGFR amplification: failed May 2019.
Toca 511 & Toca FC Gene therapy & pyrimidine analogue Tocagen NCT02414165 Toca 5 study, on top of Temodar or Avastin. In May 2019 cleared to continue to final readout, due by end 2019.
DCVax-L Cancer vaccine Northwest Biotherapeutics NCT00045968 On top of Temodar. Recruitment halted 2015 WRONG: only SCREENING! was halted: https://nwbio.com/nw-bio-confirms-phase-iii-trial-of-dcvax-l-for-gbm-brain-cancer-is-ongoing/ still no final readout.
Trans sodium crocetinate Vitamin A analogue Diffusion Pharmaceuticals NCT03393000 Intact study, on top of Temodar, biopsy-only patients: primary completion 2021.
Marizomib Proteasome inhibitor Celgene NCT03345095 EORTC-1709-BTG study, on top of Temodar: primary completion 2022.
Source: EvaluatePharma and Clinicaltrials.gov.
First to Tocagen, which disappointed investors last night by saying the Toca 5 trial would continue to the final readout, due by year end. Shares plunged 34% this morning.
The interim look was conducted after 75% of the deaths required to trigger final analysis had occurred. With so few events remaining the chances of the trial ultimately showing a survival benefit are vanishingly small.
A small band of believers remain, however. They argue that because Toca511/FC works partly by boosting the immune system a separation of the survival curves should not have been expected at this stage.
Tocagen also reckons that a survival benefit will take time to develop. But, with little reason to believe that regulators will accept anything other than a clear hit on overall survival, the primary endpoint of the trial must be met at the final analysis for unequivocal success to be declared.
Setbacks and ways forward
The field would receive a well-needed boost should Tocagen succeed, given the two phase III failures earlier this month.
Abbvie said last week that the Intellance-1 study of its antibody-drug conjugate depatuxizumab mafodotin found no survival benefit at interim analysis. This was based on data from 638 patients, and the lack of any signal must have been indisputable; the company has halted enrolment into other studies.
Depatuxizumab mafodotin was designed to treat patients whose tumours have EGFR amplification. Whether the failure was a problem with the biomarker or the ADC itself is as yet unknown.
Opdivo’s stumble with Checkmate-498, meanwhile, marked the second phase III flop for the Bristol-Myers Squibb checkpoint inhibitor in glioblastoma, after the failure of the second-line Checkmate-143 in 2017.
The anti-PD-1 antibody failed to provide an overall survival benefit at the final analysis of 498, a first-line study, the company said earlier this month, without giving further detail. Bristol’s last remaining shot here is Checkmate-548, which tests Opdivo on top of Temodar.
The odds of success must be considered low, and the 498 setback seems to confirm what many believe: that immunotherapy has yet to find its place in this cancer. This probably partly explains why Merck & Co has declined to commit serious research dollars to Keytruda in this space. Several mid-stage academic studies of the checkpoint inhibitor are ongoing in various brain cancer settings, with Merck named as collaborator in only a handful.
Still, there are signs that the company is looking for a way in: it recently initiated the phase II Leap-005 study, of Keytruda plus Lenvima, which has a glioblastoma cohort among other tumour types. Meanwhile, a signal of activity was reported earlier this year in a small academic study that is no doubt being closely scrutinised at Merck. Patients treated with Keytruda before surgery lived twice as long as those who received it afterwards.
Other immune system harnessing techniques, CAR-T for example, are being trialled in earlier glioblastoma studies with varying levels of success. And in Norway academics recently launched a fairly large phase II/III trial of a trivalent dendritic cell therapy.
Elsewhere in the pivotal pipeline
Another project is Northwest Biotherapeutics’ controversial DCvax-L, though this company has been sitting on phase III data for years now, and the cancer vaccine seems unlikely to go anywhere.
Privately held(WRONG: :DFFN) Diffusion, meanwhile, continues to enrol inoperable glioblastoma subjects into its trial of trans sodium crocetinate. The company claims that this can re-oxygenate hypoxic tumour tissues, increasing susceptibility to radiation and chemotherapy. Results are some way off, according to clinical trial database entries.
And finally marizomib, a proteasome inhibitor owned by Celgene, is being put through a pivotal trial by an academic group. Researchers hope that the agent’s ability to eradicate glioblastoma stem cells, and the fact that it is an irreversible inhibitor of all three subunits of the proteasome, give it a chance to make a mark in this disease.
The trial only started last year, so data are not imminent. But, given the setbacks elsewhere, marizomib could yet turn into glioblastoma’s biggest late-stage hope.
EvaluatePharma (The RX BIBLE!) 6/19: Next 5 Yrs Top TEN Blockbusters in Late Stage Pipeline: NWBO's stealthy technology evades.
Pharma Innovation: Risk & Reward
Oncology continues to be the main R&D focus area in the
biopharma industry.
EvaluatePharma®
finds oncology to be the area with the highest
forecasted clinical development expenditure, unsurprisingly leading
to the highest forecast number of FDA approvals of any therapy
area.
Table 12! Oncology in 2018 was $124 BLN mkt growing to $237 BLN and increasing it's market share from 14% to 19%
Keytruda is forecasted to widen the sales gap between its competitor Opdivo to over $5bn in 2024. Sitting just outside of the top 3 with predicted 2024 sales of $11.3bn,the checkpoint inhibitor Opdivo continues to have strong sales in the anti-neoplastic MAbs segment despite contrasting analyst views with regards to its trajectory as we move towards 2024
DCVax-L, Northwest Biotherapeutics
by John Carroll | [NOT DATED: Easily over 3 yrs old IMHO ]
Drug: DCVax-L
Company: Northwest Biotherapeutics
Phase: Phase III
Class: Cancer vaccine
2020 sales: $2.04 billion
Net present value: $5.5 billion
DCVax-L is a cancer vaccine, which in and of itself is grounds for controversy. Some analysts don't give this one a chance because it is a cancer vaccine based on dendritic cell technology--a field that has seen weak responses in a slate of studies. And others hate it because the company has taken the, um, unconventional approach of regularly touting individual patients' positive responses as evidence of broad efficacy. It's fine to use anecdotes to illustrate a broadly positive efficacy profile--provided you have the data in hand to back it up. Northwest Bio ($NWBO) has also trumpeted a decision in Germany to make it available to brain cancer patients. Despite the controversy, EvaluatePharma sees this one as a potential standout, a new entry that is likely to get plenty of careful attention.
Thanks Longfellow for your exhaustive reply which clearly underscores the various necessary bureaucratic procedures entailed even amongst various agencies.
My sense is that with the FDA's recent RWE and the real time coordination amongst the 4 RA's which I believe are the countries involved in the L clinicals it maybe a toss up with a lean towards the UK.
Even PRIOR to the recent FDA RWE I was leaning towards your view of NICE/MHRA vs our FDA.
With what has evolved in Immuno Oncology most especially with expensive C_ART approval arena in the last 18 months, I think would IMHO argue favorably for better DC VAX L pricings than what would have been previously possible meaning even better gross margins.
AND compared to what I had posted EONS ago about NVCR Optune (STILL VALID!) it should be a slam dunk.
Regardless of Hard Brexit etc, IMHO the urgent need for UK/Europe GBM cases will OVERCOME.
Doubtful Longfellow is ever put on the spot: Rises to EVERY Challenge: in the GENES!
DIFFERENT STROKES FOR DIFFERENT FOLKS
Thanks Gary (skitahoe) for your reply which I am responding to these excerpts:
1)
I I don't know how flexible they will be in terms of accepting changes NWBO is looking to make in evaluating the Phase 3 Trial data.
In a speech, the U.S. Food and Drug Administration (FDA)acting Commissioner Ned Sharpless said that the agency is “open for business” in taking into consideration real-world evidence (RWE) for new cancer drugs. “The FDA is always going to want to see really well-designed beautiful trials with convincing endpoints,” Sharpless said in his talk. [color=red]“If you can do a large [randomized controlled trial] with overall survival as your outcome, there is nothing better.[/color]
I believe in Europe and elsewhere the authorities are more open to thinking for themselves about how drugs are working. If you have results showing that substantial numbers benefit from the drug, even if you failed to meet pre-established goals, I believe they will see the benefits and approvals will result.
Longfellow95 re:Perhaps they're not going to bother with the FDA...
So, Europe, UK, Canada, and Japan.
Recently, Davis et al. [2] reported that the majority of oncology drugs approved by the EMA between 2009 and 2013 were “…without evidence of benefit on survival or quality of life” [2]. The authors reported that, at the time of EMA assessment, significant prolongation of survival was reported for 24 out of 68 indications (35%) and there was an improvement in quality of life for seven out of 68 indications (10%). The clinical benefit of the new drugs remained uncertain for 33 out of 68 indications (49%) after a median follow-up of 5.4 years post-marketing authorisation [2].
In England, the National Institute for Health and Care Excellence (NICE) has a mandate to appraise drugs approved by the EMA in a timely fashion with a view to making recommendations regarding their routine use in the National Health Service (NHS) [3]. This mandate makes it necessary for NICE appraisals to be undertaken using the data available at the time of, or near the point of, regulatory approval. The level of evidence that informs the EMA’s conclusion of a positive benefit/risk balance therefore plays a large part in determining the level of uncertainty present in each NICE appraisal
Lorie3168: So clearly MANY ENTITIES will need to compete with PFE and others in this immuno realm. NWBO will be that missing piece of the puzzle for some big guy. My best guess has been and still is BMY!!!!!
Visionaire becomes reality for Pfizer’s Array Bio $11 Bln acquisition:
NWBO CEO Linda Powers stated this Feb 2019 ASM:
Colo-rectal cancer is the number two cancer, second only to lung cancer. And if you’ve noticed in a lot of the publicity about immune-therapies, there’s been surprisingly little attention to colon cancer. If you also notice in the literature, checkpoint inhibitors, which are the big darlings of the pharma industry right now, have had no effect, none at all, in any patients with colo-rectal cancer except patients who have what’s called MSI, microsatellite instability a particular version of colon cancer, which only 5% of colon patients have. So we think that’s going to be a very interesting combination trial and we are looking forward to the day when we have enough resources and we can go forward with it.
The company is also testing its triple combo therapy in colorectal cancer patients.
"(The acquisition) sets the stage to create a potentially industry-leading franchise for colorectal cancer alongside Pfizer's existing expertise in breast and prostate cancers," Bourla said.
FMI develops tests to help doctors understand the genetic profile of patients' tumors and guide them to effective therapies.
[img][/img]Thanks Dan88
To quell some key DiSTURBING issues Dan88 has raised by AVII, EXwan, Jerry, PLUS ? (major known knifing SUBVERSIVES with other MOLES plus more? as I saw from THE INCEPTION)
1) National Security Risk as it relates clearly to late 2018 Huawei’s new Sawston Campus real estate deal
2) Recent Trump administration crackdown on non US citizen Chinese medical researchers at US’s leading medical research facilities(Note: I actually met one a post Phd in Immuno-Oncology working the last two years a world renown Scripps Medical Research).
3) With the above Massive issues: Will NWBO survive??
All we have are these early Feb 2019
Annual Shareholder selectively excerpted remarks that may provide some comfort:
Question 9: Is the deal with Huawei strictly a real estate deal or is there possible future collaboration? Concern about IP theft.
"Answer (LP):"Right now the Huawei deal is just the Huawei deal, it's just real estate. I don't have any reason at this moment to think it's going to be more or different than that
“Question 5: Can NWBO ovecome all of the forces that are aligned against them?
Answer (LG): "We're still here. Lots of people didn't think we would be."
(LP) "I can only give a couple of comments from a personal perspective. Everyone in this company is committed in a deeply personal way to this company and this technology, for whatever their respective, personal reasons are. Nobody would go through this degree of abuse for this long a period of time for a business, and certainly not to collect a salary paycheck, as is regularly suggested on the message boards. I personally think that if we could get through what we've gone through the last three years, I kind of think we can get through anything. The year 2015, we had come out . . . we had just made very strong presentations, I believe many parties were surprised, at AACR, the largest research conference in the world, and ASCO, the largest clinical conference in the world. We were hit with multiple class-action lawsuits, we were hit with the anonymous Internet report, we were hit with an attempted hostile takeover. We were hit with just incredible things. When we look back on it now, it's just amazing. In 2016 and 2017, were pretty horrific in their own way. And I've must say, this team, everything we do we do as a team. We do everything by unanimity. Management and the board, we have just kept doggedly putting one foot in front of the other. And we do say to ourselves not infrequently, 'well, we're not dead yet.' And we take satisfaction in the fact that somewhere there's a conference room with the bad guys in it who are saying to themselves, 'what does it take to kill these people?' Because what's been thrown at us, stock manipulation, you name it, is staggering. But, this team will never give up. We might be crushed like a bug but we will never give up.”
Baylor To Launch Glioblastoma Vaccine Study
Brain cancer vaccine clinical trial approved for Baylor College of Medicine in Houston, Texas
. ][/June 8th, 2019 – A cancer immunotherapy research group at Baylor College of Medicine announced it secured Investigational New Drug regulatory clearance through the Food and Drug Administration to perform a phase I clinical study in newly-diagnosed adult patients with glioblastoma (GBM).
Glioblastomas are malignant Grade IV tumors, where a large portion of tumor cells are reproducing and dividing at any given time. It is a highly lethal form of brain cancer, with a 5-year survival rate of less than 10 percent in most age groups, says the American Brain Tumor Association.
This vaccine technology works by “tricking” the immune system into treating cancer as it would a viral infection through the reprogramming of powerful immune cells, known as dendritic cells.
“If you can convince the immune system that the cancer is a viral infection, you can generate a more powerful anti-cancer immune response than ordinarily possible through regular vaccination techniques,” said Dr. William Decker, associate professor of pathology and immunology at Baylor, in a press release.
Sponsored Links:
DiscountsAppointmentsClinical TrialsLab Tests
Despite continued efforts over several decades to develop new therapies for glioblastoma, none have appreciably improved how long patients live.
Researchers who study glioblastoma have been hopeful that immunotherapy might be able to succeed where other therapies have not. And in laboratory studies and human clinical trials, they are leaving no immunotherapy stone unturned.
Unfortunately, several immune-based treatments that looked highly promising in early-phase studies of patients with glioblastoma have not panned out in larger, phase 3 clinical trials.
”Just the fact that we have had some phase 3 trials in glioblastoma, where for years we had a hard time getting past phase 2 trials, is an encouraging sign,”Dr. Michael Lim said, in a Cancer.org statement.SEE BELOW———————
“We’re talking about a disease that has been one of the hardest to treat in the history of oncology,” said Mark Gilbert, M.D., director of the Neuro-Oncology Branch in NCI’s Center for Cancer Research. “And trying to develop and test immune-based treatments for glioblastoma, is a whole new realm.”
Fortunately that https://clinicaltrials.gov/ct2/show/NCT00093964#contactlocation
of Cilengitide (EMD 121974) for Recurrent Glioblastoma Multiforme (Brain Tumor) -
FAILED in Ph2: https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(14)70403-6/fulltext
DIFFERENT STROKES FOR DIFFERENT FOLKS
VERIFIED IT: TOCA 511 for RECURRENT GBM
https://tocagen.com/wp-content/uploads/pipeline-10-25-17.pdf
BTW IMHO poorly written article based on having to do more work!
DIFFERENT STROKES FOR DIFFERENT FOLKS
Perhaps on closer inspection re-reading that article this is dealing with Recurrent GBM: https://clinicaltrials.gov/ct2/show/NCT02414165
DIFFERENT STROKES FOR DIFFERENT FOLKS
Looks like it is SDO’s Toca 511:
https://detroit.cbslocal.com/2012/01/31/henry-ford-pioneering-new-treatment-for-aggressive-brain-tumors/
DIFFERENT STROKES FOR DIFFERENT FOLKS
Projected $12 Bln Chemo Cancer Drug (1 of 56 ADC’s being developed in the industry: ie SGEN) by Daiichi Sanyo/AZN (keep healthy Cells!/ limit?side effects of Roche’s Chemo: Herceptin for Breast Cancer) to Replace Chemotherapy May Reshape Cancer Care
https://www.bloomberg.com/news/articles/2019-06-11/drug-to-replace-chemotherapy-may-reshape-cancer-care
DIFFERENT STROKES FOR DIFFERENT FOLKS
The sale of Cognate BioServices or Sawston facility or potential of NWBO with it’s two platforms needs to aspire to the levels cited in this Bloomberg article.
Aspirational returns:
Drug Cop Worth $400 Million After Bets on Brooklyn Real Estate
https://www.bloomberg.com/news/features/2019-06-16/drug-cop-worth-400-million-after-bets-on-brooklyn-real-estate
BTW five years ago, despite TWICE being on Empty Gas in Manhattan!! (handily self resolved) ....in 20 hrs visited 40 yrs of my episodic life that did take in gentrified DUMBO (Down Under Manhattan Brooklyn Bridge Overpass area: https://en.m.wikipedia.org/wiki/Dumbo,_Brooklyn
which was a favorite of mine for taking twilight shots of The Lower Manhattan Skyline re Financial District when I was a teenager in mid 1960’s with my Nikon Photomic F.
I obviously updated my CT/NYC photos with a Leica lens of ALL my favorites spots!
DIFFERENT STROKES FOR DIFFERENT FOLKS
Baker Brothers are undoubtedly better stock pickers than Neil. I just hope retirees in the UK are diversified enough to absorb and transition away from his fund -- unless he pulls a miracle out of his arse. Elders do not typically have time to financially recover from substantial financial mistakes.
Flipper re:Maverick, didn’t you not notice that Dr. Liau stated in April 2014 in a non-simulcasted Grand Round this will probably be a single arm study while Dr. Bosch and Dr. Ashkan have recently stated while the data is promising you need to compare arms? It is as if Dr. Liau and Dr. Bosch are not on the same page. Did you not look at the enrollment chart starting in the middle of 2008? Do you not understand the difference between recruitment and enrollment?
Simple explanation vs consternation (for yearS: par 4 the course!)
DrBala: Re: flipper44 Post# 233379
I think she just got her dates incorrect in the UW presentation. I can't explain why. In the paper (29 May 2018)
https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-018-1507-6
of which Linda Liau and Marnix Bosch are co-authors (among a bunch of coauthors), the dates are clearly stated:
Quote:
Study patients
From July 2007 to November 2015, 331 patients were recruited in the trial, comprising the intent-to-treat (ITT) population. A flow diagram depicting the flow of patients through the screening and enrollment process is provided in Fig. 1. The median time from surgery to randomization was 3.1 months.
Replies:Flipper
Sunday, 06/16/19 02:15:09 AM
Re: Dr Bala post# 233445 0
Post # of 233457
That's all one can conclude. She's done this before, but just chalk it up to being a very busy person
Saturday, 06/15/19 08:09:40 PM
Re: flipper44 post# 233423 0
Post # of 233457
OMG, one more mystery Flipper44? take a break. It's a weekend.
Maybe AVII, EX, and the like can answer your new investigational question?
They are all geniuses hanging on message board 24/7/365 for years without taking a position, long or short.
some of really sick people
Flipper re:
I dare anyone to watch Dr. Bosch June 2019 June at ASCO the Dr. Liau April 2019 at UW and not come away scratching their head about what NWBO is asking for in that SAP. I watched both twice now, after reading message board critical comments, and come away wondering if Dr. Bosch and Dr. Liau have ever met
Maverick has chosen to NOT get involved in this Woodford TEMPEST and has gone BEYOND what Smokey has dutifully documented in the post I am responding to.
So, they met with the company at that time, and they see nothing untoward in this development. Who knows what they were told.
Northwest Bio controversy intensifies scrutiny of Woodford's biotech investment chops
December 10, 2015 | By Nick Paul Taylor
"Neil has an outstanding long-term track record, but it is important not to lose sight of the fact that this has been built principally around investing in large and midsized companies that chuck out dependable dividends--such as tobacco stocks," Jason Hollands, managing director of U.K. investment adviser Tilney Bestinvest, said. The nature of drug development--and the concept of the Patient Capital Trust--means it will be years before it becomes clear whether Woodford can perform consistently as well in the very different world of biotechs and other small, unlisted companies.
Northwest Bio will have a relatively minor say in the outcome of this process. While Woodford's 28% stake in Northwest Bio means he is of vital importance to the biotech, his fund won't live or die on the performance of the investment. Having funnelled $95 million into Northwest Bio, the company accounted for 2.3% of the Woodford Patient Capital Trust as of the end of November, making it the twelfth largest position in the portfolio. Prothena ($PRTA), Oxford Nanopore and Immunocore occupied the top three spots.
Nearly all of this was delivered by Woodford’s sector allocation, rather than the particular stocks he selected from within those sectors
For all Woodford’s enthusiasm for early stage investing, he owes his stellar reputation within fund management to the big sector calls he made at the helm of his previous funds, Invesco Perpetual Income and High Income. By avoiding technology stocks at the height of the tech boom of the early 2000s, and shunning banks ahead of the 2008 financial crisis, he was been able to deliver long-term returns to investors unmatched by rivals.Nearly all of this was delivered by Woodford’s sector allocation. His most famous move, to avoid the banks in the run-up to the financial crisis, was by far and away the biggest contributor to his performance over the period. Woodford on average held 17.4% less than the market in financials over that period, a stance that delivered 25.2% of the active return.
His heavy backing of utilities delivered 22.7%, while 15.9% came from his ‘overweight’ – holding more than the market – in consumer goods, while his relative shunning of the oil and gas sector gained him a further 13.4% of that active return.
Regulators from the Bank of England and the Financial Conduct Authority (FCA) are to be quizzed by a group of MPs about the suspension of the Woodford Equity Income fund
Nicky Morgan MP, chair of the Treasury Select Committee, said she will raise the issue of the suspension of Mr Woodford’s fund when she and her colleagues on the committee meet Ben Broadbent, a deputy governor of the Bank of England on 11 June, and Andrew Bailey, chief executive of the Financial Conduct Authority (FCA) on 25 June.
She has also called on Mr Woodford to waive his management fees while his fund is being suspended.
Mr Woodford’s £3.7bn fund was suspended on Monday, meaning investors cannot access their cash. The suspension will run for a minimum of 28 days from Monday, but can be renewed.
The fund manager said he had taken the step of suspending the mandate because the volume of outflows, which ran at about £9m per working day in May, meant it was difficult for him to get the best prices when selling assets, including the tranche of unquoted assets he has committed to selling by the end of the year.
Mr Woodford’s other funds, Patient Capital investment trust and the Woodford Income Focus fund, remain open, and investors can buy and sell their investments in those mandates.
Yesterday (6 June) wealth manager St James Place removed Woodford as manager of £3bn of its assets, or about 3 per cent of its total assets under management.
This came after Hargreaves Lansdown removed the fund from is Wealth 50 buylist on Monday, with Woodford's other fund, the £552m Woodford Income Focus fund, cut from the list yesterday.
Hargreaves also waived its platform fees for investors in the fund.
Ms Morgan said in a statement today (June 6): "Investors in the Woodford Fund have been locked out of accessing their cash. Yet it has been reported that Mr Woodford is taking in nearly £100,000 in management fees a day.
"The suspension of trading has provided Mr Woodford with some breathing room to fix his fund; he should afford his investors the same space and waive the fund’s fees while the fund is suspended.
"The FCA has rightly said that it is closely watching the fund. The Treasury Committee will no doubt raise this troubling episode, and what lessons can be learnt, when we take evidence from the FCA and Bank of England."
The FCA said in a statement yesterday: "The FCA is notified of the decision to suspend funds it does not approve them.
"Suspension is not an outcome the FCA seeks to avoid if it is in the best interest of fund investors. Suspensions are recognised as a legitimate tool internationally."
GGB:This weeks Journey's END on this topic:
maverick_1 Member Level Friday, 06/14/19 02:59:26 PM
Re: maverick_1 post# 233200
Post # 233327 of 233328
IMHO NWBO CEO Linda Powers sold 4.4 mln shs at 17 cts: a small part of her NWBO shrs/options at yrend '18 at a SUBSTANTIAL LT CapLOSS to clearly OFFSET her LARGE LT CapGAIN from the MLBO SALE of Cognate BioServices (CB):
NWBO Tax Side:
1)Safe to say that the NWBO shares used for the above were BOUGHT as high as $180: see this LT chart:http://bigcharts.marketwatch.com/quickchart/quickchart.asp?symb=NWBO&insttype=&freq=2&show=&time=20
2) CEO Linda Powers sold 4.4 mln NWBO shrs @ 17 CENTS
Cognate BioServices (CB) Tax Side:
1) CB was a NEW Memphis, TN bought 2005? from bankruptcy court in the liquidation of Gene SYS?
2) In the last few years that facility was substantially expanded
3) I indicated within the last two weeks IMHO Cognate BioServices likely was sold in EXCESS of $75 mln
4) In the last 4 yrs "similar" plants were SOLD:
a)Caladrius Biosciences (CLBS)sold it's CA plant
Quote:
Hitachi Chemical Signs Agreement to Purchase from Caladrius Biosciences the Remaining 80.1% Interest in PCT for $75 Million
March 16, 2017
https://www.caladrius.com/press-release/hitachi-chemical-signs-agreement-to-purchase-from-caladrius-biosciences-the-remaining-80-1-interest-in-pct-for-75-million/
CLBS is but one of a handful of BOMBED OUT Buy recommendations by Steve G (Pyrrh + 5 other alias')
b) Novartis spent $43 mln in 2013! to acquire south NJ Dendreon plant when the later was under financial stress due to CLEAR INeptitude from MANY perspectives of CEO Mitch Gold:
Quote:
Dendreon today said it sold to Novartis its immunotherapy manufacturing facility in Morris Plains, NJ, for $43 million cash—the latest move by the troubled prostate cancer drug developer to right its own ship following more than a year of weaker-than-expected sales.
https://www.genengnews.com/topics/bioprocessing/troubled-dendreon-sells-off-nj-plant/
I will NOT spend more time on the above as I have already demonstrated in SPADES and across a wide spectrum the level of clear inexperience aside from EGO of NWBO owners or Naysayers.
That's why I always go the EXTRA MILE!
Just like what CEO Linda Powers has done in the last few years.
AND IMPORTANTLY others may react: Narcissistic through their OWN EGO or feel threatened.
ONCE AND FOR ALL:
Everything I have indicated is the furthest from that of being narcissistic or egotistic
Even without experience in a WIDE spectrum of high level encounters I have with an OPEN MIND: excelled.
That's why:
DIFFERENT STROKES FOR DIFFERENT FOLKS
IMHO NWBO CEO Linda Powers sold 4.4 mln shs at 17 cts: a small part of her NWBO shrs/options at yrend '18 at a SUBSTANTIAL LT CapLOSS to clearly OFFSET her LARGE LT CapGAIN from the MLBO SALE of Cognate BioServices (CB):
NWBO Tax Side:
1)Safe to say that the NWBO shares used for the above were BOUGHT as high as $180: see this LT chart:http://bigcharts.marketwatch.com/quickchart/quickchart.asp?symb=NWBO&insttype=&freq=2&show=&time=20
2) CEO Linda Powers sold 4.4 mln NWBO shrs @ 17 CENTS
Cognate BioServices (CB) Tax Side:
1) CB was a NEW Memphis, TN bought 2005? from bankruptcy court in the liquidation of Gene SYS?
2) In the last few years that facility was substantially expanded
3) I indicated within the last two weeks IMHO Cognate BioServices likely was sold in EXCESS of $75 mln
4) In the last 4 yrs "similar" plants were SOLD:
a)Caladrius Biosciences (CLBS)sold it's CA plant
Hitachi Chemical Signs Agreement to Purchase from Caladrius Biosciences the Remaining 80.1% Interest in PCT for $75 Million
March 16, 2017
Dendreon today said it sold to Novartis its immunotherapy manufacturing facility in Morris Plains, NJ, for $43 million cash—the latest move by the troubled prostate cancer drug developer to right its own ship following more than a year of weaker-than-expected sales.
Reality Refresher: Since Summer 2014 I did highlight The Baker Bros to Larry Smith(Smith in Stocks: SOS) at least twice in an explicitly clear comment to him on his blog and also to Flipper (since he commented many times on SOS blogs).
The Baker Bros never experienced since their inception 2002 that’s ~ 17 yrs unlike what Neil Woodford’s funds have in any of the past ~ 5 years since setting up his own shop after a sterling couple of decades at Invesco.
The reasons I offered were spot on: Neil Woodford went OUTSIDE his historical expertise.
Meanwhile there was a clear lack of consensus here: just like ALL other key pivotal NWBO points....endless debates without ACTION verdicts or preoccupied with either Pyrrh or EXwan etc etc. sort of like who’s King of the Hill....
DIFFERENT STROKES FOR DIFFERENT FOLKS
Addendum re Woodford/Hargreaves connection: The move further distances Hargreaves Lansdown from Woodford, having historically sold and promoted the investment manager’s funds through its retail investment platform. It had already dropped its platform fees for clients affected by the suspension but is facing further scrutiny by the Financial Conduct Authority and the influential treasury select committee.
The Conservative MP and committee chair, Nicky Morgan, wrote to the Hargreaves boss Chris Hill earlier this week, asking how much money the firm had made in fees from customers who had invested in Woodford’s fund.
At the end of March, Hargreaves’s customers accounted for about £2bn of £10.6bn under Woodford’s management.
As Longfellow95 saiD:TERMINAL
DIFFERENT STROKES FOR DIFFERENT FOLKS