Andrew Bary has written positively about Sarepta before. But BMRN's FDA briefing docs are so scathing of the clinical trial's efficacy outcomes, Drisapersen's safety profile, and lack of dystrophin data, that any reasonable person would conclude this drug shouldn't be approved. That's one of the big takeaways from his article.
This brings some measure of relief for DMD boys and their parents, but only fully realized when this drug is approved and accessible. It's about quality of life for them; sadly, not a cure.
For investors like us, who have been steadfastly long, it's a win that will be realized more fully in the coming days/months/years. We can wait. Boys with DMD do not have that luxury, and Bary's article, in its conclusion, makes that point well.
Small N has been the primary issue all along, and what the shorts have capitalized on.
But all of the longs here, and parents who support Etep approval, know why Etep works, and get why it will eventually be approved.
Bary sums up his piece in Barron's nicely:
"The issue with Sarepta is whether a favorable 12-boy study can be deemed conclusive or just the result of luck.
The company’s backers argue that eteplirsen deserves a chance, especially given its safety, and that a large, ongoing Phase 3 study of the drug should settle the matter of efficacy in a few years. In the meantime, 2,000 boys or more could benefit from treatment.
It’s tougher to make the case for drisapersen, given its questionable clinical and safety record. All of this suggests that the FDA should grant Sarepta’s eteplirsen accelerated approval and finally offer some hope to boys with DMD."
"The drisapersen safety issues aren’t trivial. The injection-site reaction, affecting about 75% of the boys in the trial, can involve ulcerations and permanent scarring.
Sarepta’s eteplirsen, which is delivered by infusion rather than injection, has shown no significant negative reactions at the infusion site.
The lead investigator for the Sarepta trial, Dr. Jerry Mendell, head of the gene therapy program at Nationwide Children’s Hospital in Columbus, Ohio, said last month, “This is the only trial I have ever been involved in that hasn’t had a single adverse event.” He added that he had been involved in clinical trials for more than 40 years.
Eteplirsen has a different chemical backbone than drisapersen that appears to help on safety. “The body can’t degrade it, but it can excrete it,” Wilton says of eteplirsen. When the body degrades drugs, toxins can be produced that create problems in the kidney and liver.
If both are approved, eteplirsen probably has the edge. “I haven’t met a U.S.-based family that would prefer drisapersen over eteplirsen,” Baird’s Skorney says. “The perception among patients and their families is that eteplirsen is the better drug, and perception is everything.”
Small N issues are fading like a bad paint job, lol.
Andrew Bary: "Based on the results of the Sarepta and BioMarin clinical trials, FDA comments, discussions with experts in the field, and parents of patients, we give a strong edge to Sarepta in the duel. Its shares appear sharply undervalued based on the sales and profit potential of DMD drugs."
Over the years, you have been one of the leading lights in the discussion about the differences in chemistry, MOA, and safety issues between Drisa and Etep. Your education, training and experience has contributed much to the scientific discussion on this board, and you are to be commended, sir!
Since Srpt's AdCom date is "tentative" what's the chance that if Drisa panel presages failure of approval, that Srpt's AdCom date gets moved up?
Patient advocacy for approval (which is what they are counting on), will be somewhat muted by the abysmally bad efficacy/ safety data, and equally abysmal lack of transparency to parents by BMRN about potential for significant Adverse Events. The "choice" is clear, and it doesn't include Drisapersen.
In FDA's discussion of the multi-year 12 pt study (which shows preservation of
6MWT over 177wks), FDA states these patients had typical preserved function at
baseline (given their age) so this trial “does not appear to provide any support for efficacy.”
No pulling the wool over these scientists. BMRN's smokescreen failing from every direction.
Would you like some extra sharp cheese with that whine? LOL You sound like an entitled investor, who isn't willing to do their own DD, and blame losses on others. GL
Well, maybe Ed Kaye's proclamation: "We will own the DMD space" will become reality. If Kyndrisa is rejected, for all the right reasons, then all that's left is the clear winner in this race: Eteplirsen.
"Choice" is the pc thing to say, given the dire need for something that even hints of efficacy in DMD treatment. The strategy is this: If FDA approves Kyndrisa, they must approve Eteplirsen. Parents will have a choice, and they will choose Etep.
Really? Give this lady a break. We are mere spectators to the real hardship and heartache the parents of DMD boys experience day after day, for YEARS. Don't you think Jenn's as knowledgeable about each of these drugs, their safety profile and potential efficacy, as any long-standing person on this YMB?
Parents of DMD boys are desperate for something that may work, even if the safety is questionable. Maybe their reasoning is this. If you (FDA) are willing to approve Kyndrisa, then you must also approve Eteplirsen (which is the drug we really want our boys to be on). Perhaps this is their strategy, and who is to judge them if that's the case.
I think the "choice" rhetoric is really just a PC way of not dissing a legitimate effort by a company to help alleviate the suffering of DMD boys and their families. It was a worthy effort by Prosensa, but then BMRN tried to resurrect this failed drug and pull a slick willy to get it past FDA, thinking that Srpt was too flawed to get their act together.
The "choice" is really this for DMD boys and their parents: If FDA approves Kyndrisa, we have the option of trying this drug (which may have some efficacy), until a safer and better drug gets approved. Parents are desperate to being treatment, even if it's questionable in its efficacy and has toxic side effects. If Etep is just two months behind Kyndrisa, many parents would opt to start w/ Kyndrisa and then switch. Of course, this is all assuming that FDA grants approval of a drug where efficacy is questionable and safety is poor.
*Sees expectations for drisa in DMD as "overdone", expects drug to face competition from Sarepta's eteplirsen
*Says FDA briefing docs due Friday and Nov. 24 AdCom panel will probably focus on "lackluster dystrophin data" , Failed Ph 3 study and adverse events; resulting in negative impression for drisapersen among doctors and patients will be difficult to reverse.
An analyst who totally gets it.
Thanks, jrrt1. Seems that this pretty much puts a giant question mark about that sub-set of 12 boys, under the age of 7, relative to their positive performance on the 6-MWT.
I know that their use is considered best practice, but what I don't know is at what age they are most commonly prescribed. It would be useful to know how many of the subset of 12 boys in BMRN's sub-set (where they are claiming clinical benefit) were taking steroids. If this is the case for even half, it would skew the data to show somewhat of a clinical benefit, no?
"Results of these analysis have important implications for the field's understanding of disease natural history as well as for clinical trial design. Confirmation of the previously reported age dichotomy for the sub-set of steroid-treated patients amenable to exon skipping, showing a rapid and consistent decline in ambulation, endurance and muscle function as measured by the 6-MWT in boys with DMD in boys who are equal to/or greater than 7yrs of age, while those less than 7 years old are stable or increasing in their 6-MWT distance, supports the exclusion of patients less than 7 years old from studies that aim to prognostically enrich for a declining population."
Anybody know if the sub-set of 12 boys that BMRN is attempting to show efficacy with were taking steroids at the time? Even if not on steroids, boys less than 7 years of age, do not typically show rapid decline in muscle strength, which makes their data set for these 12 boys very suspect, as many here have previously reported.
Very well said. The FDA neuro dept. is acutely aware of the importance of getting this right. Which is why Drisa will be scrutinized particularly hard and looked at from every angle. In the end, it's about 1) Safety; more than a few concerns there, and 2) Efficacy; which is legitimately questionable.
In cases where drugs that are up for approval, for patients who are dying from cancer, a drug that extends life by a few months, over current standard of care, is often approved even if adverse events are present. However, in the case of a drug that will likely be taken by a DMD boy for years, safety becomes paramount. So when you look at the "Risk/Benefit" analysis of a drug like Drisa, where the efficacy is questionable at best, and the negative side-effects are well established (at least in the short-term), what's the rationale to approve such a drug?
And, if you're an AdCom member, do you want to put your "thumbs-up" vote on a drug that potentially turns out to cause long-term health problems for a child with DMD, particularly when the efficacy is in doubt? I see a split panel vote coming.