A Look At The Upcoming BioMarin Pharmaceutical Inc. (NASDAQ:BMRN) BLA

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BioMarin Pharmaceutical Inc.(NASDAQ:BMRN) just put out its second quarter earnings for 2016, and held a conference call to address the numbers. We sat in on the call and picked up some insight into the company’s expectations for its development stage phenylalanine drug Pegvaliase. The drug is targeting an indication of Phenylketonuria, a disease that causes increased levels of phenylalanine in the blood of sufferers. Pegvaliase data from a topline hit press earlier this year, and the numbers were ok, but not perfect, and markets have been looking to Biomarin for some insight into how the company is going to respond to the results from a marketing authorization perspective. The latest call shed some light on the subject. Here’s what we know.

First, for those not familiar with this one, a quick introduction to the indication and the drug. Phenylketonuria, which we’ll call PKU, is an inherited disorder that causes an unusual buildup of the above mentioned phenylalanine in the blood. Phenylalanine is an amino acid, which are the things in our bodies that build proteins. If the levels get too high, it can result in intellectual disability issues, as well as a host of physical symptoms – seizures, skin conditions, etc. The buildup is caused by an absence of what’s called phenylalanine hydroxylase (PAH), the enzyme responsible for breaking down phenylalanine. Biomarin’s drug, Pegvaliase, is designed to seek out phenylalanine and break it down, acting as a substitute for the missing enzyme. Simple. Well, the theory is simple, at least.

The data, not so much. The trial was a pretty unique design – all patients initially took a dose of the drug, and those that showed some reaction continued into either a placebo arm of an active arm split into two dose. The primary endpoint was a reduction in phenylalanine, and 64% of patients in the active arm recorded a stat sig reduction, meaning the trial hit the endpoint.

The secondary endpoints, however, failed to record hits. These related to mood, cognitive condition, that sort of thing. Basically the primary was to show the drug had a solid MOA. The secondaries were to prove that the result of this MOA was improved symptom profiles. The active arm showed no stat sig improvement in cognitive condition over placebo (in fact, across a portion of the trial trend was weighted in favor of the latter) and so as things stand Biomarin doesn’t really have any proof that reversing the high levels of phenylalanine with its drug can counter the symptoms of the condition. In the call, the company said that the FDA has asked for some clarity on certain elements of the data before it will accept a BLA submission, and we believe these questions will probably relate to this portion of the application.

Specifically, the company is going to have to pick apart its data to show that the reduction of PHE can lead to an improvement in cognitive function, and then submit the data using this as the basis of an approval request.

It seems like a longshot, but it’s not really. The drug is probably going to target the most severe of the patient population, so it may be approved as a second line therapy. A currently approved drug that Biomarin creates is currently SOC, and this is just designed as a supplement to dietary control. It works in most cases, but the company has developed this one with the goal of removing the need for dietary control. As such, it can probably apply for an approval with the agency based on the fact that the most severe cases don’t have too much of an option (dietary control can be difficult given the number of foodstuffs that contain phenylalanine) and this drug is meeting that need.

Whatever happens, and whatever the FDA needs from Biomarin before it will give the drug a green light, Biomarin believes it can get the BLA with the agency before the close of this year, or at the very latest, during the first quarter of next.

One to watch, if only to see how the FDA is treating BLAs like this right now.

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