BioMarin Pharmaceutical Inc. (NASDAQ:BMRN) just announced that the FDA has delayed its PDUFA for the companies lead Batten Disease candidate, meaning the agency won’t get round to offering up a decision until April 27, 2017. The news has knocked the company down a bit, and heading into the US session on Wednesday, it looks as though we might see a little bit more selling pressure as markets digest the news.
We see this as an opportunity to pick up an exposure to BioMarin at a small discount. The PDUFA extension looks like pretty standard procedure, and markets have sold off a bit on the headline, as opposed to the detail.
First, a quick look at the drug and the indication. Many reading might be new t oBatten Disease. It’s very rare neurodegenerative disease that begins in childhood, and is genetically inherited from parents. Its symptoms are early onset, and can include vision loss, blurry vision, seizures and – a little later down the line, spine curvature, hyperventilation, muscle mass loss severe motor skill issues. There’s no cure, and its terminal.
BioMarin’s drug is called Brinuera, and it targets a specific form of Batten called CLN2. The disease is caused by mutations in various genes, and as the name of this subtype suggests, the mutated gene in this instance in CLN2. This mutation leads to the deficiency of an enzyme called tripeptidyl peptidase 1 (TPP1), which in turn leads to the excessive storage of lysosomal material that would normally be metabolized by the enzyme. This material builds up in various organs, creating the symptoms and issues associated with the condition. The drug is an enzyme replacement therapy. It’s a recombinant version of the TPP1 enzyme, designed to perform the function of the enzyme it replaces – the TPP1 enzyme that the mutated CLN2 gene doesn’t produce correctly.
Data supporting efficacy is very solid. After 81 weeks post treatment, patients that underwent Brinuera therapy had motor-language (ML) scores representing substantial attenuation of disease progression compared to natural history. The data that underpins this statement follows data from a 48 week follow up, which showed a similar result.
Safety and tolerability proved no real issue, and given there is no currently available treatment for what is essentially a terminal sentence, the agency will likely be more than willing to let s number of AEs slide just to get a treatment to market, and then let the physicians and patients decide whether they are happy to accept the AEs (assuming they are not too serious, of course) in return for some level of reprieve.
So what’s the issue?
Well, the FDA requested that the company submit some updated efficacy data from its ongoing continuation trial as part of its initial assessment of the drug’s BLA. BioMarin’s data looked to support the initial hypothesis, so the request seemed not to impact the drug’s chances of approval. However, upon acceptance of the additional data, the agency decided that the scope of the data qualified as what’s called a substantial revision. Substantial revisions mean the agency is allowed to extend its review period, and that’s what has happened here.
The review division in question. The Division Of Neurology Products, is pretty infamous for extending PDUFAs like this, so it shouldn’t be looked on as indicative of the drug’s chances of approval or failure come review date. The FDA is just like any other governmental or private entity – it is subject to review, and performance quotas. These reviews have become particularly harsh over the last ten years or so, as public calls for quicker and more efficient drug review have come to the fore. One of these review points is meeting PDUFA dates.
Just as with any other entity, therefore, the agency will look for ways to avoid falling short of this review. One such method is to extend the PDUFA, and one way to extend the PDUFA is to file the additional data as a substantial amendment.
This isn’t to say there’s anything under-hand going on, it’s pretty standard practice, but there is no doubt an element of self interest in the decision.
Whatever the driving factors behind the action, however, the important thing to recognize is that it says nothing about how well, or not, Brinuera performs. The bottom line is we’ve got a drug that seems to work, and safely, targeting a currently unmet need. Come PDUFA in April, we expect a green light from the agency.