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$SPRY / $AQST: FDA Advisory Committee Votes in Support of Favorable Benefit-Risk Profile for neffy® (Intranasal (IN) Epinephrine) for the Treatment of Allergic Reactions (Type 1), Including Anaphylaxis
https://finance.yahoo.com/news/fda-advisory-committee-votes-support-230100445.html
$AQST
Aquestive will most likely benefit from this decision as it will simplify the eventual approval of their product (sublingual epinephrine film).
https://www.healio.com/news/allergy-asthma/20230315/sublingual-epinephrine-film-beats-syringes-autoinjectors-in-time-to-maximum-concentration
re: Epipen: $AQST epinephrine sublingual film
Aquestive Therapeutics Announces Positive EPIPHAST II Trial Data for AQST-109 When Compared to EpiPen
AQST-109 median time to maximum concentration (Tmax) of 12 minutes was faster than EpiPen® Tmax of 22.5 minutes
AQST-109 repeat dosing provided significantly higher drug plasma concentrations with a Tmax of 8 minutes after administration
Changes in systolic blood pressure and heart rate were similar after a single dose of AQST-109 when compared to a single dose of EpiPen
End-of-Phase 2 meeting with FDA scheduled for fourth quarter 2022 and remaining clinical studies will commence thereafter
Source: https://finance.yahoo.com/news/aquestive-therapeutics-announces-positive-epiphast-110000982.html
re: AQST
“We are surprised to receive this notification from the FDA. We accepted all of the Agency’s label edits for Libervant last week and, as the Agency stated in its notice today, there is no additional information needed from the Company at this time. Following the labeling discussions, we believe the package we submitted satisfies all of CDER’s requests,” said Keith Kendall, Chief Executive Officer of Aquestive.
---
What could be the reason for the delay and will it rather take days or weeks to solve this problem?
Imo good data for a small company like LPTX (market cap below $150M) but also 4 grade 5 AEs they did not explain in their PR.
DKN-01 + tislelizumab + capecitabine/oxaliplatin was well tolerated according to their abstract (no related G3/4 toxicities).
Trial is not on hold.
Hopefully more info on Thursday, 2:30 a.m. ET (ESMO presentation) and at their conference call on Friday, 8:00 a.m. ET.
LPTX - Leap Therapeutics to Present New Data from the DisTinGuish Study of DKN-01 Plus Tislelizumab at the ESMO 2021 Congress
Mon, September 13, 2021, 12:00 PM
- DKN-01 plus tislelizumab and chemotherapy demonstrated compelling activity in first-line patients with gastric or gastroesophageal junction cancer
- In patients who received a full cycle of DKN-01 therapy, the ORR was 68.2%, with 90% ORR in patients with DKK1-high tumors
- Further results will be presented at the ESMO 2021 Congress from September 16 to 21, 2021
- Company to host conference call on Friday, September 17, 2021 at 8:00 a.m. ET
https://finance.yahoo.com/news/leap-therapeutics-present-data-distinguish-100000549.html
FYI: Leap Therapeutics and BeiGene Announce Exclusive Option and License Agreement for DKN-01
Jan 03, 2020, 08:53 ET
[...]
Under the terms of the agreement, Leap will receive an upfront cash payment of $3 million from BeiGene in exchange for granting BeiGene an option to an exclusive license to develop and commercialize DKN-01 in Asia (excluding Japan), Australia, and New Zealand, and will be eligible to receive an additional payment from BeiGene upon BeiGene's exercise of the option following initial proof-of-concept studies. Additionally, Leap is eligible to receive payments from BeiGene based upon the achievement of certain development, regulatory, and sales milestones for a total deal value of up to $132 million, together with tiered royalties on any product sales of DKN-01 in the licensed territory. BeiGene will also make a $5 million equity investment in Leap as part of the contemporaneous $27 million equity financing.
[...]
https://www.prnewswire.com/news-releases/leap-therapeutics-and-beigene-announce-exclusive-option-and-license-agreement-for-dkn-01-and-leap-announces-27-million-equity-financing-300980854.html
https://clinicaltrials.gov/ct2/show/NCT04385771
Recruitment Status: Suspended (security concerns based on preliminary results from preceding CYCOV-I-study suggesting higer mortality in cytokine adsorption group)
Last Update Posted : March 15, 2021
Earnings Call Transcript
Cytosorbents' (CTSO) CEO Phillip Chan on Q4 2020 Results
https://seekingalpha.com/amp/article/4412713-cytosorbents-ctso-ceo-phillip-chan-on-q4-2020-results-earnings-call-transcript?source=feed_f&utm_campaign=twitter_automated&utm_content=article&utm_medium=social&utm_source=twitter_automated&__twitter_impression=true
That said, we recently just met again with the Agency and believe that we are now aligned on the positive benefit-risk profile of the therapy and the additional clinical data needed to support approval.
[...]
There is another point that makes U.S. FDA Breakthrough Designation even more meaningful. Last month, the Centers for Medicare & Medicaid Services (CMS) announced the Medicare Coverage of Innovative Technology pathway that will provide national Medicare coverage as early as the same day as FDA market authorization for breakthrough medical devices, where coverage would last 4 years. This program is expected to speed adoption of CytoSorb, if approved, across the U.S. for this application.
CytoSorb for reducing risk of bleeding during cardiac surgery
Medtech innovation briefing [MIB249]Published date: 02 February 2021
Summary
The technology described in this briefing is CytoSorb. It is used for the removal of the blood thinning medication, ticagrelor, from blood during on-pump urgent or emergency cardiac surgery.
The innovative aspects are that it is the first medical device that can be used to remove ticagrelor from the blood during urgent or emergency cardiac surgery. Using CytoSorb in emergency cardiac surgery could reduce resource use for management of bleeding complications, and in urgent cardiac surgery could reduce length of hospital stay before the procedure and the use of adjunctive bridging treatments.
The intended place in therapy would be as an alternative to surgical management of bleeding in emergency surgeries (when ticagrelor is not removed) or as an alternative to a 5- to 7-day delay in urgent surgeries for natural ticagrelor washout.
The main points from the evidence summarised in this briefing are from 6 studies (4 observational studies, 1 bootstrap analysis based on a retrospective case series and 1 case study) including a total of 209 people. They show that CytoSorb may be more effective than no CytoSorb adsorption in people having cardiac surgery.
Key uncertainties around the evidence or technology are that 3 small comparative observational studies focusing on emergency cardiac surgery were included. In most studies people were given ticagrelor or rivaroxaban. No comparative studies were included for people having urgent cardiac surgery. None of the studies were done in the UK.
The cost of CytoSorb is £1,500 per unit (excluding VAT). The resource impact would be less than standard care for emergency cardiac surgery (a UK cost-utility analysis reported a cost saving of £3,941 for CytoSorb compared with no removal of ticagrelor), and less than standard care for urgent surgery (about £1,575).
Source: https://www.nice.org.uk/advice/mib249/chapter/Summary
re: NY-Times and Nature
https://www.nytimes.com/interactive/2020/science/coronavirus-drugs-treatments.html
https://www.nature.com/articles/s41581-020-00352-9
Btw., one of the authors, Swapnil Hiremath, is very active on twitter:
https://twitter.com/hswapnil
Now is the right time to introduce Donald Trump to Cytosorbents Corp. and their blood filter.
He will love them.
Tonight, @FLOTUS and I tested positive for COVID-19. We will begin our quarantine and recovery process immediately. We will get through this TOGETHER!
— Donald J. Trump (@realDonaldTrump) October 2, 2020
Part D prescription drugs are also affected: New version of Executive Order (not online yet).
https://publicpool.kinja.com/subject-executive-order-on-lowering-drug-prices-by-put-1845042893
Executive Order on Lowering Drug Prices by Putting America First
Issued on: September 13, 2020
https://www.whitehouse.gov/presidential-actions/executive-order-lowering-drug-prices-putting-america-first/
Trump just signed a new Executive Order to lower drug prices.
Just signed a new Executive Order to LOWER DRUG PRICES! My Most Favored Nation order will ensure that our Country gets the same low price Big Pharma gives to other countries. The days of global freeriding at America’s expense are over...
— Donald J. Trump (@realDonaldTrump) September 13, 2020
Terumo Corporation
https://en.m.wikipedia.org/wiki/Terumo
Terumo Cardiovascular and CytoSorbents Collaborate to Commercialize CytoSorb® in Ten U.S. Hotspot States under Emergency Use Authorization for COVID-19
https://finance.yahoo.com/news/terumo-cardiovascular-cytosorbents-collaborate-commercialize-110000565.html
$CTSO A recent study showed the use of CytoSorb resulted in 100% survival vs. 57% mortality rate in the control group. #COVIDTreatment https://t.co/imIOTMJFsF
— Marty Milner, Pattern Recognition Specialist (@martymilner) July 8, 2020
BARDA partnering with SepsisAlliance to develop educational webinars on connections between #COVID19 and #sepsis. Early sepsis treatment & monitoring for long-term effects can improve patient outcomes & #SaveLives.
BARDA partnering with @SepsisAlliance to develop educational webinars on connections between #COVID19 and #sepsis. Early sepsis treatment & monitoring for long-term effects can improve patient outcomes & #SaveLives. #solvingsepsistogether https://t.co/D09jQn2gOX #SolvingSepsis pic.twitter.com/8mQ2qys3CH
— BARDA (@BARDA) June 11, 2020
Cytosorbs mentioned in The New York Times
https://www.nytimes.com/2020/06/11/health/coronavirus-cytokine-storm.html
For example, the Food and Drug Administration has authorized the use of a cartridge that continually filters excess cytokines from the blood, similar to the way a dialysis machine removes toxins. The purified blood is then pumped back into the body.
The device, called CytoSorb, is about the size of a drinking glass and is filled with coarse polymers, each roughly the size of a grain of salt. Every grain, or bead, has millions of pores and channels that add up to a surface area of roughly seven football fields and filter out molecules roughly the size of cytokines. One cartridge can purify an entire body’s blood volume roughly 70 times in a 24-hour period.
Bigger objects like cells go around the beads and are unaffected, and smaller things like electrolytes go straight through, said Dr. Phillip Chan, the chief executive of CytoSorbents Corporation, which makes the device. CytoSorb may also remove some proteins that the body needs.
But “in a life-threatening illness when you have a cytokine storm,” Dr. Chan said, “it’s more or less a race to remove what will kill you versus the temporary inconvenience of removing things that your body manufactures all the time anyway."
In Europe, where CytoSorb has been commercially available since 2013, it has been used more liberally. But in the United States, the device had been allowed only for patients who had exhausted all other options. Even now, during the pandemic, its use is authorized only in coronavirus patients who are critically ill, with imminent or confirmed respiratory failure.
Dr. Stephan Ziegeler, who leads a specialized pulmonary intensive care unit at a hospital in Ibbenbüren, Germany, has so far treated eight people with CytoSorb. (Since 2018, he has received speaking fees from CytoSorb’s manufacturer, totaling 5,000 euros, or about $5,600.) Of these people, three have been discharged, three are being weaned off ventilation and two have died.
Patients with bacterial sepsis typically need a maximum of three cartridges — one per day at $1,200 — but coronavirus patients have such astronomical levels of cytokines, Dr. Ziegeler said, that some have needed dozens of cycles, with two fresh cartridges per day.
“It seems that Covid-19 has a prolonged cytokine storm — a prolonged, really effective inflammatory state compared to other sepsis states,” he said.
Some patients who are severely ill have only moderately high levels of cytokines, however, and Dr. Ziegeler said it was not yet clear whether they would benefit.
He recalled the case of one 45-year-old physician who had been hooked up for three weeks to an extracorporeal membrane oxygenation machine, or ECMO, which removes blood from the body, infuses it with oxygen and then returns it to the body. Coronavirus patients who get to that point tend to stay sick for a long time, Dr. Ziegeler said, and since they are already having their blood pumped out to be oxygenated, adding on the CytoSorb filter does not add risk.
So, even though this patient did not have levels that were “sky-high,” doctors treated him with 14 rounds of cytokine adsorption. The man responded well, Dr. Ziegler said, and was discharged soon after.
CytoSorb is not the only mechanical approach being used; the F.D.A. has also authorized the use of another device, called Oxiris, for coronavirus patients. And there are plans to try CytoSorb in combination with tocilizumab.
With an estimated population of 1.2 billion, India is the world's second most populous country after China.
Registry of CytoSorb Therapy in COVID-19 ICU Patients (CTC REGISTRY)
Recruitment Status : Not yet recruiting
First Posted : May 18, 2020
Last Update Posted : May 18, 2020
Brief Summary:
The CTC Registry collects patient-level clinical data on CytoSorb hemoadsorption provided to COVID-19 ICU patients via integration of the CytoSorb device into ECMO, CRRT, or hemoperfusion extracorporeal circuits under the FDA Emergency Use Authorization for this CytoSorb device use. The intent of the registry is to gain understanding on how CytoSorb hemoadsorption provides clinical benefit to COVID-19 ICU patients.
Study Type : Observational [Patient Registry]
Estimated Enrollment : 1000 participants
Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration: 30 Days
Official Title: Registry of CytoSorb Therapy in COVID-19 ICU Patients (CTC REGISTRY): Registry of Patient-level Clinical Data on CytoSorb Hemoadsorption Provided Via Integration of the CytoSorb Device Into Extracorporeal Membrane Oxygenation (ECMO), Continuous Renal Replacement Therapy (CRRT), or Hemoperfusion Extracorporeal Circuits in COVID-19 ICU Patients
Estimated Study Start Date : May 2020
Estimated Primary Completion Date : May 2021
Estimated Study Completion Date : August 2021
source: https://clinicaltrials.gov/ct2/show/NCT04391920?term=Cytosorbents&draw=2&rank=3
PS: I hope we will get a press release today... (see i.e. $DVAX)
Thanks. To make your message complete, here is the Authors’ response:
Herbert Schöchl, Marion Wiegele, Eva Schaden
To the editor
We would like to thank Honore et al. for their interest in the Austrian interdisciplinary consensus statement on diagnosis and treatment of traumatic brain injury (TBI) patients on oral anticoagulants. The author state that bleeding patients on ticagrelor and non-vitamin K antagonist oral anticoagulants (NOACs) might benefit from extracorporeal removal of these drugs using CytoSorb® haemoperfusion (CHP). Indeed, in emergency open-heart surgery CHP of ticagrelor and rivaroxaban resulted in reduced bleeding complications and less drainage volume compared to a historical control group [5].
Neither platelet transfusion nor desmopressin has been proven to be efficient in ticagrelor-associated bleeding. An in vitro study revealed that CHP removed >?99% of ticagrelor from human blood samples within 3?h [2]. Albumin represents an alternative approach to bind ticagrelor. An experimental study using high-dose albumin spiking of blood samples containing ticagrelor resulted in a significant improvement of platelet function [6]. This might be considered a less invasive and more rapid option compared to CHP.
The role of CHP as an effective and easy to use alternative for NOAC removal in major bleeding is currently unproven. Experimental data revealed that within 1 h of CHP, 91.6% of rivaroxaban was effectively eliminated from the blood [4]. No data for edoxaban and apixaban or for the thrombin inhibitor dabigatran have been published so far.
For dabigatran reversal, the humanised antibody fragment idarucizumab has been proven efficient. The drug is widely available and its cost is acceptable. Thus, idarucizumab clearly represents the therapy of choice in dabigatran-related bleeding. The evidence is less clear for the specific Xa inhibitor antagonist andexanet alfa. The drug costs are considerable, prothrombotic side effects have been reported and the clinical efficacy of andexanet alfa is not fully proven. A current meta-analysis revealed that prothrombin complex concentrate (PCC) showed comparable haemostatic efficacy to andexanet alfa, but PCC is currently not approved for Xa-inhibitor reversal [7]. Thus, before suggesting CHP in bleeding TBI patients, we would highly recommend PCC as a more rapid, widely available, and less invasive alternative for Xa-inhibitor reversal compared to CHP.
We agree with Honore et al. that CHP might represent an interesting alternative to eliminate ticagrelor. For bleeding patients under NOACs, a variety of specific and unspecific reversal agents are available. Thus, before recommending an invasive procedure such as CHP in TBI patients, both safety and efficacy have to be confirmed in vivo.
source: https://ccforum.biomedcentral.com/articles/10.1186/s13054-020-02922-6
You can find a transcript of the call at: https://seekingalpha.com/article/4343440-cytosorbents-corporation-ctso-ceo-phillip-chan-on-q1-2020-results-earnings-call-transcript?part=single
Here is what was said about scaling up manufacturing.
Andrew D'Silva
Okay. Thank you very much for the update on that. I just have two more quick questions. You provided an update in an 8-K, I believe it was last month and at the end of the 8-K you referenced expanding your manufacture – or scaling your manufacturing capabilities.
I was just a little bit curious on what we should be thinking about there. Would you be looking to establish a new facility or just add capacity within the existing facility? Any color in that would be useful. And also if you could just tie in where you are in your capacity utilization right now that would be interesting too?
Phillip Chan
Sure. Let me turn over to Vince Capponi who's been doing a great job in terms of managing that up taking capacity. Vince?
Vincent Capponi
Yes. Thank you, Phil. So just let me take that and just a couple of parts here. First, the capacity we're currently at, obviously with this surge in requirements related to COVID-19, we've really cranked up to seven days a week, 24 hours a day, right now in order to meet the demand as Cathy and Phil mentioned, we had a backlog at the end of Q1. And obviously the orders are still coming in. So we're working very rapidly to fulfill that.
We said we could supply essentially an $80 million business. We'll give exact percentages, but we're using a significant portion of the capacity of the plant. Obviously we're taking a look at potentially what the next level of expansion is going to be. Given what we've just experienced now and the fact that Christ is continuing to drive sales in Germany in the core business and treating sepsis, et cetera, we need to take a look at that and we would probably not do it within this existing facility because it's starting to get pretty large from a scale standpoint and this is really not quite designed to do that kind of work here. So we would be looking outside this facility.
But we are currently evaluating that and obviously looking very closely what the trend is in the market for us to best determine what that path will be going forward.
Webinar: COVID-19 Patient Transport and Cytosorb Use - YouTube
More details about the D2000 Adsorption Cartridge
https://www.fda.gov/media/136839/download
Btw. the manufacturer Depuro LLC is 100% owned by the Swiss company Marker Therapeutics AG, not Marker Therapeutics Inc ( $MRKR ).
New IEEE Spectrum article featuring Cytosorb:
"Brita Filter for Blood" Aims to Remove Harmful Cytokines for COVID-19 Patients
[...]
“This is a fascinating idea,” said Jessica Manson, consultant rheumatologist and honorary senior lecturer at University College London Hospital. She is one of six co-authors of a 13 March letter to the journal The Lancet arguing that doctors need to be aware of so-called cytokine storm syndrome when treating critical COVID-19 patients.
[...]
Manson says she recently talked with an official at University College London Hospital to see if they could set up a clinical trial to test a blood filtration idea for other cytokine storm-like conditions. Although this conversation was “pre-COVID.”
The evidence is still preliminary as to whether CytoSorb will be effective as an emergency COVID-19 intervention. That said, Manson says she’s at least convinced of the concept behind the therapy. “I think this is genius,” she says. “It’s something we should really work on.”
https://spectrum.ieee.org/the-human-os/biomedical/devices/blood-filtration-tech-removes-harmful-cytokines-covid19-patients
What is your view on Cytosorbents Corporation (CTSO)?
Their product, CytoSorb®, is an extracorporeal cytokine adsorber designed to reduce the "cytokine storm" or "cytokine release syndrome".
It is approved in the European Union and widely used in Germany.
This is from their latest press release:
Over the past two weeks, multiple patients with at least respiratory failure, shock, or kidney failure, in multiple hospitals in Wuhan, China have been treated with CytoSorb. Based on preliminary positive feedback on patient outcomes, we have responded to a request for additional devices and have now delivered a second shipment of CytoSorb devices to our partner in China, intended for new critically-ill COVID-19 patients.
https://www.prnewswire.com/news-releases/cytosorbents-provides-update-on-cytosorb-and-covid-19-coronavirus-activities-301022338.html?tc=eml_cleartime&fbclid=IwAR2zyZ3RvPwg1mBM96MbV1BSnFaO9NLs0Q6cylzAxROPYvbjqO5bp68064U
re: Cytosorb / HA380 / Coronavirus / Claudio Ronco, MD
Coronavirus Epidemic and Extracorporeal Therapies in Intensive Care: si vis pacem para bellum
[...] However, according to information collected from Chinese colleagues who faced a large proportion of patients with complicated COVID-19 syndromes in their ICUs, a significant benefit seems to have been obtained with the use of direct HP with cartridges containing highly biocompatible sorbents and microporous resins [26]. Such therapies, designed to remove the excess of circulating cytokines, seem to have displayed a remarkable benefit in terms of hemodynamic support and organ function recovery [2]. The suggested scheme of application of HA380 cartridges (Jafron Biomedical Co., China) was 2-1-1, that is, 2 units utilized for 12 h in the first 24 h and 1 unit per day utilized for 24 h in the following 2 days. In Europe, we had matured some experience with the use of Cytosorb© cartridges (CytoSorbents Corporation, NJ, USA), exactly for the same purpose of controlling deadly inflammation in critically ill and cardiac surgery patients [27, 28]. {...]
source: https://www.karger.com/Article/FullText/507039
Dr. Chan continued, "We are also pleased that on March 3, 2020, the National Health Commission in China issued the official, updated "Diagnosis and Treatment of New Coronavirus Pneumonia (7th Version)" guidelines, which now includes the following translated statement as a treatment recommendation, "For severe and critically ill patients with cytokine storms, in order to remove inflammatory factors, block "cytokine storms" and increase "blood purification treatment".
Germany has 543 confirmed Coronavirus cases and no deaths.
Have they been using CytoSorb to treat Coronavirus-patients?
Other countries are doing much worse than that.
https://www.worldometers.info/coronavirus/
AFMD: new Corporate Presentation (May 29, 2019)
https://www.affimed.com/wp-content/uploads/20190529_Affimed_Corporate-Presentation.pdf
AFM13 @15th INTERNATIONAL CONFERENCE ON MALIGNANT LYMPHOMA (15-ICML)
Lugano, Switzerland
oral presentation (June 22, 2019): 12-month data for AFM13 + Keytruda® (pembrolizumab)
+ poster: Interim data for monotherapy in TCL
see also: http://www.lymphcon.ch/icml/website/doc/15-ICML_ScientificProgram_website.pdf (page 21)
H2 2019 (not H1 2019): Initiate registration-directed study (monotherapy in TCL)
study update: AFM13+pembro in HL completed, AFM11 in NHL terminated
Study of the Combination of AFM13 and Pembrolizumab in Patients With Relapsed or Refractory Classical Hodgkin Lymphoma
Recruitment Status : Completed
First Posted : January 28, 2016
Last Update Posted : May 16, 2019
https://clinicaltrials.gov/ct2/show/NCT02665650?term=affimed&rank=2
Safety Study to Assess AFM11 in Patients With Relapsed and/or Refractory CD19 Positive B-cell NHL
Recruitment Status : Terminated (Non-favorable risk/benefit profile with studied dosing regimen)
First Posted : April 8, 2014
Last Update Posted : May 16, 2019
https://clinicaltrials.gov/ct2/show/NCT02106091?term=affimed&rank=3
This was already announced March 27th, 2019 =>
Sure - but the main intention for Affimed is to deal it to a partner who may do whatever they want with AFM11.
— `((,(Dieter 'Hovekamp)))🇺🇦👥🤝👥🇷🇺 ☮️🕊️ (@dhovekamp42) April 24, 2019
FYI the whole answer from the last $AFMD conference call https://t.co/DPdQjQwLQG pic.twitter.com/G09GPTjV7j
AFMD: new Corporate Presentation (May 7, 2019)
https://www.affimed.com/wp-content/uploads/20190507_Affimed_Corp-Pres_.pdf
No partmership with Nektar Therapeutics anymore (page 3 + 26).
See also Presentation from April 4, 2019: https://www.affimed.com/wp-content/uploads/20190405_Affimed_Corp-Pres_.pdf