Biotech Values

[iwfal]

SRPT

1) I predict that meaningful SAE will show up for Etep or its cousins for other exons. All but one of the oligonucleotides run in big RCTs have shown bad SAE related to oligo technology that was not readily apparent in the smaller, single arm or shorter ph2s. (interesting note - the only oligo that did not show oligo related toxicity in their ph3 RCT was miplomersen. It's interesting because it has really unpleasant SAE of another form - huge injection site reaction - and it has target releated SAE in liver enzymes. Finally note that in the REMs it has apparently shown thrombo, so it is not actually immune to standard oligo SAE.)

There is an interesting piece recently published in Scientific American (of all places) by someone who is making FOIA requests of the FDA with regards to Sarepta. The most interesting piece of the article, from this perspective, is:

For example, in several of the documents, frequently encountered adverse events—side effects and other negative consequences that occur during a treatment—are occasionally redacted. In some cases, other sources give us a hint of what these adverse events likely are. For example, one document states that "The most commonly reported [adverse events] included procedural pain, oropharyngeal pain, [REDACTED], cough, nasal congestion, and extremity pain," Luckily, one table below a nearly identical redacted section is intact, and it implies that the censored portion is drawn from the following: hypokalemia (low levels of potassium), vomiting, "balance disorder," headache, fever, back pain or a certain kind of blood clot known as a hematoma. (Vomiting and balance disorders are listed as possible side effects on eteplirsen's label.) In other cases, though, it's all but impossible to figure out what the FDA is attempting to block us from seeing: an updated listing of adverse events in a follow-up study says that "the most common [adverse events] overall were procedural pain [REDACTED.]" Also expunged from the document were possible indicators of kidney problems and issues related to blood clots.

And I would suggest the most interesting piece of this excerpt is what I put in italics since the two most common SAE for oligonucleotides are renal issues (almost universal) and blood disorders (although generally thrombocytopenia). In any case the FOIA results will be interesting - especially as the RCT populations get bigger.

Full article is here: https://www.scientificamerican.com/article/is-the-fda-withholding-data-about-a-controversial-drug-to-protect-its-manufacturer/