Veru Inc. - VERU
Will the FDA grant an EUA and eventually approve Sabizabulin?
I pointed this name out a while back, and eventually took it off my list once all of the hype had died down. Well, it’s now back, so I thought I’d stick it back on the radar.
Back on April 11th VERU announced that their oral COVID drug candidate worked so well during their phase 3 trial that the independent monitoring committee administering the trial recommended cutting the trial short for ethical reasons.
The company then met with the FDA about submitting an Emergency Use Authorization (EUA) based on the trial results, which it submitted in due course on June 7th.
A couple of days ago, VERU announced that the New England Journal of Medicine Evidence published the full trial results. So finally we get to see under the hood all of the numbers the company has so far not provided.
https://evidence.nejm.org/doi/full/10.1056/EVIDoa2200145
Now, the NEJM Evidence is not the same as the NEJM. As they state in the announcement for NEJM Evidence, not everything submitted to them is worthy enough to get published.
https://www.nejm.org/doi/full/10.1056/NEJMe2118588
If you peel back some of layers on the VERU trial and take a look at some of the numbers, one might begin to see why the NEJM took this approach and why that may not bode well for a future EUA approval, much less an outright FDA approval. The first doubts that things may not be up to snuff came from this NY Times article, which didn’t really delve into any of the specifics, other than to just say that the trial size was rather tiny all things consideredl and that cutting off trials so early is typically a bad idea. They suggested that a larger and more expansive trial would have been a better idea.
https://www.nytimes.com/2022/07/06/health/covid-drug-cancer-sabizabulin.html
The study size was rather tiny. Of the 176 patients that were originally slated to take part in the study, only 150 eventually moved on to take part, with 98 in the trial group and 52 in the placebo group, and not every one of those was counted in the final data processing. The trial also was not conducted solely in the United States, but rather had over 50% of participants come from either Brazil, Argentina, Bulgaria, or Mexico. From the thousands of patients coming down with this monthly, they couldn’t have had this much trouble getting volunteers. The trial didn’t require anyone to give up any currently prescribes therapeutics like Remdesivir, but simply to also take Sabizabulin in conjunction with it.
https://evidence.nejm.org/action/showPublicationFigures?doi=10.1056%2FEVIDoa2200145&figureId=f1
The “demographics and clinical characteristics of patients” data has a few odd numbers. While some of the descriptive characteristics like Sex, Age, and Race, are all roughly in the same ballpark, the differences in some of the more meaningful measures start to stand out.
https://evidence.nejm.org/action/showPublicationFigures?doi=10.1056%2FEVIDoa2200145&figureId=t1
Take the WHO 9-point ordinal scale for improvement scores. Here, the placebo group had double the percentage of WHO 6 participants, which were pretty much the worst off of the patients that they would accept into the study.
Oxygen saturation, which was required to be under 94% for the trial, had some differences. The trial group’s range was from 84 to 100 while the placebo group was 48 to 100. Perhaps those extra WHO 6 folks already on ventilators skewed those numbers lower.
We also know obesity, measured here by the BMI, has been an important factor. BMI levels for the placebo group ranged from 22.9 to 69.4 while the trial group was 20.2 to 61.7. While the means and medians each skewed in the favor of the placebo groups, those outliers are the one’s that were likely most at risk.
When it comes to COVID, the FDA has been rather sloppy in what type of data they will or will not accept and consider, and studies that would ordinarily be thrown back at companies are now routinely granted approval. Whether or not any of this ends up mattering remains to be seen, but as more therapeutics get approved perhaps the FDA will begin to revert to the FDA of old. Then again, perhaps this new politicized FDA is here to stay.