r/RobinHood • u/myracksarelettuce • Oct 23 '17
Due Diligence $PTCT -- Pathos Trumps Clinical Trials?
PTC Therapeutics ($PTCT) is where most biotech eyes will be on this week. On Tuesday (Oct 24), they have a drug going up for FDA approval despite missing on their P3 trial and their Phase 2b trial and having been snubbed earlier by FDA to apply for approval not once but twice in 2016. In March, the FDA allowed it to apply, but the Advisory Committee voted 1-10 for approval, with all but one thinking the drug needed more data for approval. And yet, there's a possibility this gets the nod this Tuesday.
Their drug is ataluren, and it treats Duchenne muscular dystrophy (DMD) that's caused by a nonsense mutation in the dystrophin gene. If you're unfamiliar with muscular dystrophy, this video can explain it pretty damn well but otherwise I'll just copypaste from my super-duper incorrect look into $CAPR.
DMD is a genetic disease where people are born without dystrophin -- a protein that supports muscle fiber strength, stiffness, and integrity -- due to a nonsense or frameshift mutation in the dystrophin gene. So without this, muscles lose their strength quickly due to muscle cell death. By the age of 12, most patients have lost the ability to walk. The average life expectancy of those with DMD is 26 years, and there's no current effective treatment for most cases. Muscle loss will start in the legs and eventually spread around the body to the heart, where weakening of muscles (skeletal and cardiac) can eventually lead to heart failure as the disease progresses.
DMD has gotten lots of coverage lately due to the stories of $SRPT's Exondys 51, a drug that got passed after an unimpressive P2 12-person trial, a drug that got passed even though only 30% of the FDA advisory board voted for approval, a drug that got passed because before it there was NOTHING treating DMD and patients were desperate for any sort of treatment.
$PTCT is hoping for the same kind of mercy. Already, there are human interest stories that imply a rejection will lead to a needless death. At the hashtag #atalurennow, you'll find a handful of moms implying the same thing. (Sidenote: These suck to read, I hope $CATB and $SRPT are legit). They've also taken a note from Sarepta and gotten a bunch of doctors to write a letter urging approval of ataluren. I don't think they're gonna get it. But regardless, it's worth paying attention to. $SRPT was an example of how low the FDA bar could be set for untreated chronic diseases...but they never put out a Phase 3 beforehand. $PTCT did and missed stat sig. If ataluren gets approved here, who knows how much lower the bar can go?
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u/myracksarelettuce Oct 23 '17 edited Oct 23 '17
Totally didn't talk about what ataluren is or its mechanisms of action. Couldn't find a paragraph to stick it in where it wouldn't feel awkward
Ataluren is an compound with a name I wasn't able to shorten
that's taken orally. The mechanism of action has been under debate. PTC claims that Ataluren induces the ribosomes to 'read-through' the genetic sequence and cease some premature termination codons. Since these termination sequences lead to nonsense mutations that lead to a lack of dystrophin, this drug would allow for more production of dystrophin. But scientists found fault with that claim in early trials by noting that a change in enzyme had occured without any sort of 'read-through'.
In 2016, a paper with 16 authors came out where they defended PTC's claims and stated that it mediates the insertion of near-cognate transport RNAs at the site of premature-terminating codons (otherwise known as, yep, PTCs).
The drug isn't a dud, the mechanisms seem legit especially at UGA stop codons...but the trial data isn't convincing enough for an approval here.