BioMarin Heads to FDA With Mixed Data For Rare Disease Drug

BioMarin Pharmaceutical had a setback in January when a gamble it had made on a Duchenne muscular dystrophy drug failed. The company has been rallying around data from other drugs in its pipeline, however, and one of its most important tests was a Phase 3 study that produced results this morning.

Those data are mixed. On one hand, the drug, known as pegvaliase, met its main goal in a Phase 3 study of 86 patients with Phenylketonuria, or PKU. The drug bested a placebo in lowering patients’ levels of the amino acid phenylalanine, which builds to dangerous levels in people with PKU and can lead to a number of other health problems, including mental impairment. There was a 62 percent difference in blood phenylalanine levels between the two groups.

On the other hand, pegvaliase didn’t meet its secondary goals. The drug didn’t lead to a statistically significant benefit in inattentiveness or mood. A small exploratory sub study including nine patients also only showed “trends of improvement” in the cognitive function of nine of them. Still, the study tested these measures over the course of eight weeks. San Rafael, CA-based BioMarin (NASDAQ: [[ticker:BMRN]]) said in a statement that longer-term evaluations it has conducted of patients in the Phase 3 program provided “supportive evidence” of a link between reduced phenylalanine levels and an improvement in attention span.

As has been the case before, the most significant side effect associated with pegvaliase is hypersensitivity (about 39 percent of patients, compared to 14 percent on placebo), an immune reaction to the drug. Other side effects included joint pain, headaches, and fatigue. No one dropped out of the study.

“Treatment with pegvaliase has resulted in dramatic [phenylalanine] decreases down to within normal levels which have not been achievable in the past with other PKU treatment options,” said study investigator Cary Harding, a genetics professor at Oregon Health & Science University, in a statement.  “Blood [phenylalanine] reductions at this level have the potential to have a meaningful impact on the lives of PKU patients.”

The question is whether all this is good enough for regulators. BioMarin said that it hopes to file for approval of the drug by the end of the year, but that is “subject to further discussions” with the FDA. In a research note, RBC Capital Markets analyst Michael Yee called its approval prospects “murky and uncertain” given the drug didn’t hit its secondary goals and the cognitive improvement trend was exploratory only. He added that the path forward in Europe is “not completely clear yet as well and needs better visibility.”

One in every 14,000 babies born in the U.S. is diagnosed with PKU every year, and the available treatment options are a strict diet and BioMarin’s own sapropterin (Kuvan), a pill that only works in about half of patients. That drug generated $239.3 million in revenue for BioMarin in 2015. Pegvaliase is an injectable treatment given once a day meant for the folks that don’t respond to sapropterin. A couple of young Boston-area biotech startups, Synlogic and Rubius Therapeutics, are also developing treatments for PKU, although neither have entered clinical testing as of yet.

The PKU results mark the second important data release for BioMarin since January, when the FDA rejected its Duchenne drug drisapersen. Earlier this month, BioMarin released positive data from study of a drug for a form of the genetic condition Batten disease, and aims to apply for approval. But there’s some risk there as well. The study is a small, open-label trial, and while RBC’s Yee wrote in a previous note that the drug appeared to produce a “major treatment effect,” he also added “whether FDA will approve this is not clear.”

BioMarin shares dipped just over 5 percent in pre-market trading on Monday. The company is holding a conference call this morning to discuss the PKU results.