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The article discusses making 100 million doses using conventional egg based virus cultivation. Neither Moderna or Pfizer make an egg based influenza vaccine AFAIK. Sanofi and GSK would be the players here.
Enanta's patents for Paxlovid and EDP-235 are what are known as "composition of matter" patents. For a pharmaceutical company, these are the best kind of patents to have as the patentee has exclusive rights to the use of that molecular entity.
Just a guess on my part but I think the headcount reduction may not be from layoffs but from the elimination of open positions. Enanta had around 20 open positions on the careers section of their website that were recently removed. If you consider approved positions that are not yet filled to be headcount, then cutting these openings could be construed as a 15% reduction in the workforce.
Did it occur to you that they may not have been able to get the trial design they wanted?
As I said, I expect the CD approval to be based primarily on the strength of the clinical data package. While Revance has had some execution problems with manufacturing, IMO they have done a very thorough job of conducting the clinical trials. I don't recall any FDA issues with glabellar (sp?) lines clinical trials. There are others here who could better comment on the quality of the CD trial data but from my recollection of the results I would consider approval to be highly likely. Maybe that equates to a 90/10 probability of approval.
I think your 60/40 probability of approval for CD is too pessimistic. There is not likely any facility inspection required as the bulk process issues were resolved with the Daxxi approval and they just had a prior approval supplement for the Ajinomoto fill/finish facility granted. I would expect the review of the CD indication to be based almost exclusively on the clinical trial data.
Why would they need another inspection?
I was clearly wrong about the reps claim and completely unaware of the composition of the peptide, so thanks to you and Boraborak for educating me on that. I understand that your comments regarding the peptide were probably made tongue-in-cheek but still people should know that Daxxify is a bacterial protein toxin just like Botox and all the others.
BTW the issue of immunogenicity of botox/daxxi you raised is one I have wondered about since they are both administered parenterally and repeatedly. I think the reason why they do not elicit an antibody response is that the amount of protein is so minuscule. I do remember reading a long time ago that people who suffered from tetanus and survived still did not have a protective immune response. I'd be interested if anyone here knew more about it.
I was not disputing what you said. My comments were to Mouton regarding the nature of Daxxify, and what may or not be possible based on what I have heard about the manufacturing process for current botulinum toxin products.
I think you are a little off base here. I think the rep was referring to the fact that Daxxify does not use human serum albumin which could potentially be contaminated with HIV proteins as it is a blood derived product. ASAIK, Daxxify is also botulinum toxin that has been treated to attach a peptide that results in the longer duration. It is also derived from a bacterial culture of Clostridium botulinum and likely contains small levels of other intrinsic contaminating proteins from the bacterial culture. Clostridium species produce some of the most potent toxins known to man and those toxins are all proteins.
All the politicians, university deans, corporate executives, etc, who issued vaccine mandates regardless of prior Covid infection could not seem to grasp that possibility.
Minor point Dew but Paxlovid is a drug not a biologic. The panel will be reviewing an NDA not a BLA.
The reason why mRNA vaccines can be produced so quickly is they don't involve a fermentation or cell culture process for making the antigen. I don't know any details of the current mRNA Covid vaccine processes, but I am pretty sure they are chemically synthesized and not grown in fermenters or bioreactors. Conventional vaccines require significant time in developing the cell line, and significant time for developing a process specific for that cell line once it becomes available. Operation warp speed would have been pretty much impossible with anything other than an mRNA vaccine.
Considering that Enanta owns the patent on Paxlovid, they should be able to make their own clinical trial supply if necessary.
Agree with you on this one Dew. There is no statutory requirement to apply cGMP regulations to the execution of development batches. However, if they have an SOP that indicates they must use the deviation process for certain development runs, then they can be dinged for not following their SOPs. In either case, these are minor issues IMHO.
If the current crop of Covid vaccines were highly efficacious, no one would worry about whether some child was also vaccinated. Smallpox and polio vaccines were highly efficacious, and conferred life long immunity once primary immunization was given. Efficacy of the mRNA vaccines is below 50 % after six months. And no one knows how long the booster doses will work. Vaccine company execs are making statements about annual boosters. What are they basing that on? A five year old child would have somewhere around 30 injections before he is old enough to buy a beer. How safe is it to get even a third booster? Nobody knows. The probability of a severe cardiac adverse event goes up ten-fold between the first and the second Pfizer shot. How much does it go up between the first and the tenth dose? I don't know what your family situation is, but you should do a little more due diligence before subjecting your children and grandchildren to this outrageous human experiment.
Here is what I don't understand. Considering the vaccine's weak efficacy, questionable safety, and the low risk of serious disease among most people, why are politicians and public health authorities so adamant about vaccine mandates for everyone, along with draconian restrictions on the freedom of people to go about life as they please?
Not true. The data are from the Moderna and Pfizer clinical trials, and it speaks for itself. And the data support the argument that for most people the vaccines will have a minimal affect on mortality. For children, I think there is a fair probability that the vaccine will be responsible for more mortality than Covid.
Dr Allon Friedman made an argument in his article that the threat from Covid for most people has been grossly exaggerated. Dewophile in his response to you bolstered Dr Friedman's argument.
In Australia, the military is rounding up Aborigines in the desert and putting them in camps where they will be quarantined and force vaccinated. In the USA, MSNBC TV celebrity, Jim Cramer is foaming at the mouth ranting that the US military should be doing the same to the unvaccinated here.
Read this for a little bit of sanity:
https://brownstone.org/articles/vaccine-mandates-unscientific-divisive-and-enormously-costly/
This isn't going to be good either. Keep in mind the study is after two doses.
https://t.co/ft6Ike37ze?amp=1
https://theconservativetreehouse.com/blog/2021/11/27/explosive-interview-uk-cardiologist-highlights-link-between-mrna-vaccines-and-heart-disease-while-noting-researchers-withholding-data-fearful-of-losing-funding/
I see no reason why this product could not receive EUA in 2022 if it performs well.
Superior can be measured in areas besides just efficacy. Safety and convenience are two areas where the Enanta product should have a big advantage. And if you keep in mind, that this is going to be given pre-hospitalization, safety and convenience will matter more to the majority of the target market who are not at high risk of serious disease.
I think you are way off here Dew. By everything I can see, the Enanta product is far superior to the Pfizer product. Enanta may have to partner in order to get the regulatory access they need to streamline approval but they should be able to do that on very favorable terms. If Pfizer results (which are from an interim analysis) hold up, you can forget Merck or Roche, the contest is between Enanta and Pfizer. Yes, Enanta needs to get into the clinic, but small molecule trials on a therapeutic are much easier to conduct than RCTs on vaccines. The Phase 1 Enanta is planning is on 75 healthy volunteers, how hard should that be to enroll?
I'm pretty certain these are not recombinant strains.
That is my best guess. How big an issue it is would depend on what changes were made. If they added something to the seed without disclosing it in a filing to FDA would be major. My guess is whatever changes they made were considered to be benign by Revance. A more conservative approach would have been to shorten the expiration dating on the working seed and change nothing. They had around nine years of production with it so that is more than adequate to work with in routine production. And that could still be an option to discuss with FDA when they do have their Type A meeting.
The preparation of the WCB or possibly the seed expansion of the WCB.
https://www.fda.gov/media/153014/download
So here is the FDA 483 report. It is heavily redacted but if you read observations 1 and 2, it is clear that they are related. Observation 1 is regarding stability of the WCB and it references an investigation as well as a CAPA 21-07. A CAPA is a "corrective and preventive action" which is a standard pharmaceutical quality system requirement for addressing significant issues identified during an investigation of deviations. That same CAPA is referenced in observation 2 which addresses changes made to the commercial process. The 483 says "There was a redesign of the Growth Performance (redacted) as a time course...." There is also some language regarding the implementation of an "in process control" to address the growth issue. So it isn't possible to know exactly what changes were made but I do think a careful reading of the 483 makes it clear what step was changed and why.
I think you are way off base in your thoughts of what was changed in the process. I had a chance to see the actual redacted 483 today and now have a better understanding of what may have been changed in the process and why. It likely had to do with problems with the WCB and nothing to do with patent work arounds or process efficiency to reduce COGs. The production process for Daxi is likely a fairly low tech small scale operation in comparison to a typical biopharmaceutical operation. The good news for investors is that this product is very, very cheap to produce. Some scale-up from clinical batches to commercial scale production batches is routine and should not have been a big issue with FDA even if it was done with Daxi as long as there was good data to support it.
I will post the 483 tomorrow and give a little more perspective on what I think the issues are and what would be needed to remediate them.
Yes
Certainly, but without knowing more specifics we can only guess.
This one should be an easy fix. Commit to produce and qualify a new working cell bank, and also to do a stability study to establish a more realistic expiration date for the working cell banks. Of course, I'm just guessing but I would say my guess is as good as (any probably better than) most here.
I think it very unlikely that there would have been any genetic drift due to maintenance of the cell banks. Typically, bacterial seed cultures used for biologics manufacturing are stored as lyophilized ampoules for the master cell bank and as deep frozen sub-cultures for the working cell bank. The lyophilized ampoules have a very long shelf life but the frozen working cell banks will gradually lose viability when stored. My guess is Revance chose a long (ten year?) expiration date for the working cell bank without any data to support it. They then began to experience poor growth in the production vessels as the working cell bank aged and lost viability, but were not experienced enough to realize this when they investigated.
It is not a fair comparison to lump Covid in with the other childhood diseases for which the US requires immunization. Even though most of the viral vaccines given are attenuated they do not result in disease symptoms and once the immune response is achieved, the immunity is complete and long lasting, or at least for the period when the child is at highest risk.
Seasonal influenza is a much more serious disease in children than Covid. Yet there have never been mask mandates, school closings, mandatory vaccination or anywhere near the fear mongering that the public is currently being subjected to. The current Covid vaccines do not protect against infection, disease, or transmission of the virus. Although they can be characterized as generally safe they are not completely safe. And they have only been demonstrated to be effective for a matter of months.
That isn't the message that came from Fauci or JB.
Also, when asked on CNN by Sanjay Gupta recently if people with natural immunity from prior infection should be included in the OSHA vaccine mandate, Fauci responded that he had no firm answer to that. Does anyone truly believe that the number one infectious disease expert in America hasn't given that issue enough thought to be able to offer an opinion?
https://www.bmj.com/content/374/bmj.n2101/rr-0
Kudos to Philip Krause and Marion Gruber for doing something to restore credibility in the FDA. Although too bad they had to resign to do it.
https://els-jbs-prod-cdn.jbs.elsevierhealth.com/pb-assets/Lancet/pdfs/S0140673621020468-1631529799470.pdf
https://www.medrxiv.org/content/10.1101/2021.08.30.21262866v1
I think it depends which age/sex cohort you are talking about. Keep in mind many colleges and universities have mandated Covid vaccines for all students including those who have natural immunity because of prior infection. Prior Covid infection was an exclusion criteria for participating in the clinical trails so safety data on this group was not obtained.
There is a reason why it usually takes about ten years and not six months to develop and test a new vaccine. The current vaccines were not adequately tested for either safety or efficacy IMO. On efficacy, would these have been even approved for EUA if it was known that they would lose close to half of their efficacy in less than six months? Even now, there is no good information on how often boosters may be needed. Trudeau of Canada was boasting the other day that he was in negotiations to purchase up to sixty million doses of vaccines annually to cover the period up to 2024. That is two boosters a year. And yes you are absolutely right Jbog there is no long term data on safety. So why not make them mandatory for every man, woman, and child in America?