If there is a controversial subsector of biotech at the moment, it’s the Duchenne’s muscular dystrophy (DMD) space. yesterday, we discussed the advisory panel recommended an FDA declined for Sarepta Therapeutics Inc’s (NASDAQ:SRPT) lead DMD development candidate, Eteplirsen. We opined that in order for the agency to approve the drug, it would have to break its own protocol and do so on one of the smallest pivotals in modern drug development history.
We followed this up with the suggestion that this doesn’t necessarily mean the agency won’t approve Eteplirsen – it is under considerable pressure (albeit controversially) to do so from families and sufferers the condition, rooted in the fact that their currently exists no other treatment option.
After markets closed on Tuesday, however, we got word that a second company working on a DMD treatment just advance its development program. When the FDA meets on May 26 and delivers its decision on Eteplirsen, one of the factors taken into consideration will be those drugs that are currently behind the aforementioned in the development process, but in the not too distant future, could provide a superior alternative. the drug that this second company – London based Summit Therapeutics PLC (ADR) (NASDAQ:SMMT) – is working on will almost certainly be one such consideration. With this in mind, here is a look at the science behind the drug, and what’s the latest step forward means for both Summit, and the DMD space as a whole.
So, the science. Summit’s candidate is called Ezutromid, and is part of a family of drugs called utrophin modulators. The most advanced clinical stage treatments, including Eteplirsen, worked to increase the level of dystrophin in DMD patients. The root cause of the condition lies in a mutation that creates dysfunctional dystrophin, and working to overcome this dysfunction is a logical approach. With utrophin modulation, however, things are little different. When muscle fibers are created, utrophin is used to provided and help develop structure during the early phases of creation. After the early phase completes, however, our bodies stop producing utrophin and start producing dystrophin. In DMD sufferers, this is where the problems start. Summit is hoping to use Ezutromid to ensure that – in DMD patients – production of utrophin doesn’t stop. The latter is structurally identical to the former, and they both perform almost identical functions, so – in theory, at least – as long as one or the other remains functionally active, muscle fibers shouldn’t break down and the underlying cause of DMD symptoms should be fixed. Interesting, right?
That is the theory. So what did to the latest updates tell us about the development process, and what are we looking for going forward? Further, what might this mean for Eteplirsen’s chances, come the end of May?
The announcement reported that the FDA had has cleared Ezutromid’s investigational new drug (IND) to expand an ongoing Phase 2 proof of concept clinical trial called PhaseOut DMD to trial sites in the US. The trial is ongoing in the UK, and while it is still early days (primary endpoint as things stand relates to pharmacokinetics rather than efficacy) the trial could pave the way for a much larger global trial if primary and exploratory suggest efficacy. Interestingly, one of the exploratory endpoints is the same as that of Eteplirsen’s phase III primary – walking distance post treatment.
The trial is set to start during the third quarter of this year in the US, and while we don’t have a fixed topline date, it’s is expected to last 48 weeks, meaning we should get some confirmatory data before the close of 2017.
So what does this mean for Sarepta and Eteplirsen? Well, the phase 2 is set to enroll 40 boys between ages five and 10 years, which already exceeds the scale of the Eteplirsen phase 3 by nearly 4 times. Of course, with Eteplirsen’s PDUFA set for the end of next month, the FDA won’t have any conclusive data as to the efficacy of Ezutromid ahead of its decision deadline. However, that there is a much larger scale trial in this indication ongoing, and especially given its alternative mechanism of action, there is every chance that the FDA will issue a CRL requesting an expansion of Eteplirsen’s trial that falls in line with that of Ezutromid. Speculation, of course, but a reasonable conclusion nonetheless.
Whatever happens, the DMD space is going to be an interesting one to watch across the next 24 months. That treatment alternatives are finally getting to the late stage can only be a good thing for sufferers and their families, and as a speculative investment prospect, it makes for very interesting analysis.