Still licking Duchenne wounds, BioMarin makes an early run at Batten drug OK

BioMarin CEO Jean-Jacques Bienaimé

Just weeks after getting snubbed at the FDA over its "contradictory" case for the Duchenne muscular dystrophy drug drisapersen, BioMarin ($BMRN) is winding up for another try at an approval with new data gathered from a small, single-arm study of its new therapy for a type of Batten disease. And analysts have quickly begun raising a fresh set of questions about whether the biotech is setting itself up for another rejection.

Investigators for BioMarin say they tracked clear signs of disease stabilization among 23 patients with rare and lethal cases of CLN2 disease, a type of Batten disease, after 48 weeks of treatment in a Phase I/II study. Treated with 300 mg of cerliponase alfa--a recombinant human tripeptidyl peptidase 1 (rhTPP1)--BioMarin reported that their rate of decline in language and motor function was about 80% less than the expected rate of decline based on historical averages.

The study did not use a placebo arm to compare the drug's effect, a point which will earn careful scrutiny at the FDA.

Investors certainly weren't convinced. By late morning BioMarin's shares were trading up a bit more than 1%.

The drug is designed to be inserted into the fluid around the brain, spurring TPP1 enzyme activity that eradicates the toxic material that causes CLN2. And BioMarin says it plans to file applications for an approval on both sides of the Atlantic in the next few months, confident that its researchers can make the case that the drug can significantly delay the rate of decline most patients can expect.

Coming just after the FDA's resounding rejection of drisapersen, though, BioMarin is facing some skepticism over whether it has the data needed for an approval. Barclays' Geoff Meacham says that the 36-week abstract that BioMarin posted yesterday was "encouraging" but possibly insufficient to warrant an OK at this point.

"While a stat. sig p-value, we question if these data will be sufficient for regulatory approval--especially in light of recent setbacks in DMD (Kyndrisa, eteplirsen, and atalauren)," Meacham noted. "We believe that FDA could require some sort of a placebo-controlled trial to approve cerliponase alfa."

Safety data will also be carefully scrutinized.

"Seven (29%) of the subjects experienced a total of ten serious adverse events (SAEs) assessed as related to cerliponase alfa by the study investigators, which included eight events of hypersensitivity and two events of infusion-related reactions," the company stated. "Eight of the ten related SAEs were Grade 1 or 2 in severity, and two were Grade 3 (hypersensitivity). Seven (29%) patients experienced 15 device-related adverse events: 14 out of 15 were Grade 1 or 2."

Meacham and others have pegged peak potential sales at about $300 million. But BioMarin could also use some added respect now in order to make a case that it has the late-stage pipeline necessary to move the company forward.

"BioMarin is humbled by the substantial benefit that cerliponase alfa has shown for many of the children with CLN2 disease in this trial. Maintaining one or two points on the CLN2 disease-specific rating scale could mean the important difference between a child being able to continue to walk and talk or not," said Dr. Hank Fuchs, the chief medical officer of BioMarin. "We have pushed out a medical frontier by developing a potential first enzyme replacement therapy administered directly into the brain ventricles for a form of Batten disease. We are planning to apply for regulatory approval in the U.S. and Europe with this study, which is a very rapid registration approach justified by compelling data in this devastating disease."

- here's the release