Markets just learned that the advisory panel tasked by the FDA with reviewing and recommending the approval of, or the turning down of, Sarepta Therapeutics Inc’s (NASDAQ:SRPT) Eteplirsen – the company’s development stage Duchenne’s muscular dystrophy (DMD) candidate – has recommended against approval as things stand. The drug has long been on the radar of those who keep an eye on the biotech space, and the advisory panel meeting was not only watched closely by biotech investors, but also a large number of individuals and families with a vested interest in the agency’s final decision. The whole situation has brought up a scenario that the FDA would rather not be involved in – that is, caught in the middle of emotional sufferers of the disease and their families, and the statistical standards by which it normally requires development stage drugs to adhere. As mentioned, the advisory panel recommended against the FDA’s approving of Eteplirsen, despite what amounted to a record showing to the panel review meeting and up to four hours of debate and deliberation (compared to the usual one hour review). Of course, the FDA doesn’t have to follow the opinions of its review panel – which begs the question, what should the agency do now?
Let’s take a look.
First, then, a quick review of the data. Across the sample population, which was double blinded, Eteplirsen met both of its co-primary endpoints – an increase in the distance DMD sufferers were able to walk, post treatment, and an increase in functional dystrophin. There were few, if any, serious adverse events across the trial, and all patients carried through to completion.
From this paragraph, there looks to be no reason why any review panel would recommend the non-approval of the drug in question. But there is a catch. The trial on which Sarepta’s Eteplirsen NDA is based only tested twelve patients. Further, only eight of these underwent Eteplirsen treatment from day one – the other four were placebo.
To get an FDA approval based on the treatment of 12 patients is unheard of. It’s very difficult to prove the long-term efficacy of a treatment with such a small sample size, however rare the target indication.
And therein lies the problem. There’s no arguing that the drug was effective in its albeit small population, but this is no guarantee that – when expanded – this efficacy will replicate.
The review panel believes Sarepta should conduct an expanded trial, but this in itself poses some problems. Take, for example, the patients currently undergoing Eteplirsen treatment as an extension to the initial trial. How many of these will want to volunteer for an expanded trial when there is a very real risk that they will end up in the placebo arm?
The situation is this: there are no currently available treatments for individuals with this condition, and a large anecdotal evidence suggests efficacy.
Sarepta even brought in some data from Europe that used DMD sufferers, and their respective symptoms as they relate to the two already mentioned co-primary endpoints, in an attempt to use this data as an expanded placebo arm. When compared to this European data, the Sarepta patients in the US demonstrated a statistically significant improvement in walking abilities, and dystrophin expression. The European data was historical in nature, however, and there have been numerous cases in the past where historical data has been proven not representative of current data.
So, what should the agency do?
It is in a position where sufferers and their families want Eteplirsen approved, even if its efficacy is only marginal, and demonstrable in small population, because it offers an option where there are currently none.
On the other hand, the agency was put in place to stop drugs that have not yet proven effective in a wide patient population hitting markets, and in turn, stop members of the public being fooled into paying large sums of money for treatments that might not work.
By the strictest definition of the agency’s raison d’etra, therefore, the FDA should really decline Eteplirsen while Sarepta undertakes, and demonstrates efficacy of the drug as part of, an expanded population.
There is a first time for everything, however, and this may be the occasion on which the agency breaks protocol and flexes slightly in response to patient demand – demand that is playing a bigger and bigger part in the global healthcare space every year.
Definitely one to watch – PDUFA is set for May 26.