$RLFTF DD by Sparks (copy) : Sharing a summary of the interview with Dr. Javitt I put together for myself because of the confusion this week with PRs etc. Dr. Javitt appeared to be confident and very encouraging.
Regarding primary endpoint: The primary endpoint is recovery from respiratory failure - meaning patients get better and go home - it is NOT mortality. This was discussed with the FDA early on in the study, along with a timeline of 60 days based on what they saw with Dr. Youssef's open label study at Houston Methodist last fall. The 28 day timeline was included originally because that has been the historical standard since the 90's for ARDS studies but it isn't really relevant anymore. The FDA told them that ultimately they care about how patients feel, function and survive.
Regarding the timeline: the last patient was enrolled on Dec 24 and Day 60 for that patient will be February 20th. At Houston Methodist, they achieved statistical significance and a larger difference between days 28 and 60.
Regarding the release of topline data to the public: they are tracking and cleaning it in real-time and not waiting for the last patient but it can still take a week or two after the last patient is finished to look at the entire dataset and clean up discrepancies etc.
Regarding the EUA: they don't have to submit a new application and they are building off of the previous application from last fall by adding important new data from this study. The FDA told them they wanted randomized control data to make a decision about the EUA and so they are providing that now. The drug did not have a meaningful safety database previously either until now, and so they can now say with confidence that it is safe.
Regarding additional information: For additional supportive information they are having radiologists review x-rays in a blinded manner to see if they are consistent with the open label results.
Regarding the PRs: They released the PR this week because it is material information that investors should be aware of and it is significant because there is a precedent with Remdesivir as it was approved for EUA based on a statistically significant reduction in hospital days and Zyesami shows this as well in a more significant way.
Regarding the significance of secondary endpoints like reduced hospital days, reduced ICU days and improved NIAID scores : They are showing statistical significance across the board. There are obviously the financial and logistical benefits to having people go home earlier, but more importantly for the study it shows that something biological happened to get them better and home sooner. they now need to look at the data further to calculate the time to resolution for respiratory failure.
Regarding manufacturing: they have teamed with Nephron Pharma for the inhaled sterile products and are feeling good about that, they have built a supply chain and can supply as much raw material (aviptadil is the raw material) as needed in North America and Israel now and within a few months will have enough for the rest of the world.
Regarding marketing: Robert Besthof is handling building up a commercially capable company. Some large partnerships will be announced in the near future regarding this. He did say that Cardinal Health is the logistics partner that can get the drug anywhere overnight.
He isn't too worried about marketing - if the FDA grants the EUA people will know about it and Drs will want it - the drug speaks for itself. Regardless they have a team, a plan in place and some partnerships they will be announcing.
He talked about a bunch of other stuff like requirements for NDA (new drug approval) versus EUA, the inhaled trial they have started with UC Irvine and will announce additional study sites in the next few weeks, how Zyesami is included in the I-SPY trial supported by Barda that will compare multiple promising new drugs against each other (this will be the inhaled version), they are actively looking into chronic covid longhaulers and how this can help with acute lung injury. He said that even if covid disappears in a year ARDS continues to be a problem and the previous studies for this didn't advance mainly due to no commercial supply or long term formulation available. He said that Zyesami should work with the new variants because of what it targets as opposed to vaccines that target a specific protein. They are working on standing up a research program in the next couple of months to measure this.
A great call and put my mind at ease - I hope this helps you if you don't have time to watch the video.
