Here’s Our Take On The Latest BioMarin Pharmaceutical Inc. (NASDAQ:BMRN) Submission

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It is Independence Day in the US today, meaning the US financial markets are closed until the market open on July 5. This doesn’t mean we don’t have anything noteworthy happening in the biotechnology sector, however. At the end of last week, we got word on a number of major updates; updates that, depending on how they play out, could be pivotal for the companies (and the assets) they address.

In yesterday’s biotech analysis coverage, we highlighted the Intellipharmaceutics International Inc. (NASDAQ:IPCI) advisory panel meeting scheduling and the resubmission of a Biologics Licensing Application (BLA) by Aeterna Zentaris Inc. (NASDAQ: AEZS) for Macrilen (macimorelin) in patients with growth hormone deficiency in adults (AGHD).

Today, we’re going to look at another BLA submission, but this time by multi-billion-dollar biotech behemoth BioMarin Pharmaceutical Inc. (NASDAQ:BMRN).

On Friday, June 30, BioMarin reported that it had submitted a BLA for one of its lead development assets to the FDA in the US, a drug called pegvaliase, which is (and forgive us for the jargon here, we’ll clear things up shortly) what’s called a PEGylated recombinant phenylalanine ammonia lyase enzyme product.

It’s designed to reduce blood phenylalanine levels in adult patients with a condition called Phenylketonuria (PKU) who have uncontrolled blood Phe levels on existing management. Phenylketonuria is a rare genetic condition that translates to a patient having uncontrollably high levels of phenylalanine in their blood. Phenylalanine is an amino acid that – in healthy patients – is broken down and removed as waste. The buildup of phenylalanine, as occurs in patients with PKU, can result in a whole host of different symptoms, including mental disorders, visual problems, seizures and intellectual disability.

The idea behind the treatment is relatively simple.

Normally, an enzyme called PAH is responsible for breaking down the phenylalanine in the body. PKU is generally caused by a PAH deficiency and treatment with pegvaliase is essentially an enzyme replacement therapy, designed to top up (or more actually, account for the deficiency of) PAH enzyme.

That’s the MOA, what about the drug in practice?

The application that BioMarin has submitted is a bit of an unusual one, in the sense that it is not strictly based on data that demonstrates an improvement in the underlying condition. What it has shown, however, is that a consistent and steady increase in levels of the PAH enzyme is brought about on the back of consistent administration of the drug in question, pegvaliase, and the assumption is that this maintained increase should translate to an improvement in the side effects or symptoms of the condition itself. In other words, it is a sort of surrogate type treatment.

So, what are the chances of approval?

Well, while the data hasn’t necessarily shown improvement in disease severity, it has performed well against the above-mentioned PAH increase endpoint and the FDA has indicated in the past that it would be willing to approve this drug if the company could prove that it was both safe and effective in terms of inducing an increase in PAH. BioMarin has done this and so – as things stand – there doesn’t seem to be any clear reason why the agency won’t approve the drug come decision day.

Of course, this is development stage biotechnology and nothing can be taken for granted. We don’t have the actual submission, and so there may be certain elements of it that negate chances of approval going forward.

On numerous occasions, we have seen things like manufacturing issues come into the picture and affect what otherwise seemed like a sure thing application. There’s every chance that this might happen with BioMarin’s latest submission and therein lies the risk associated with picking up an exposure to the company ahead of the drug’s approval date.

With that said, however, this is an (albeit rare) unmet need and one for which the current standard of care treatment doesn’t really make the grade in terms of being able to claim effective treatment. With this drug demonstrating a relatively clean safety profile (there was some anaphylaxis demonstrated, but nothing that cannot be treated post-occurrence) we think there’s a good chance of it bringing in a regulatory green light this year.

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