- BioMarin Pharmaceutical has withdrawn its application for approval of its Duchenne muscular dystrophy (DMD) drug in the E.U., after discussions with the European Medicines Agency "clearly indicated" a key committee would recommend rejection for the drug, the company said Tuesday.
- The FDA rejected the drug, known as drisapersen or Kyndrisa, four months ago for failing to demonstrate substantial evidence of effectiveness in treating DMD.
- BioMarin will also discontinue development for three follow-on products to drisapersen, BMN 044, BMN 045, and BMN 053, which are in mid-stage trials for specific forms of the muscle-wasting disease.
BioMarin made a big bet on drisapersen in 2014 when it acquired Prosensa Holding N.V. for $680 million to gain access to its DMD assets, headlined by drisapersen. Even though drisapersen had already failed a phase 3 study, prompting GlaxoSmithKline to back out of development, BioMarin thought it would be able to push forward with a retrospective analysis of sub-populations.
Since then, the company has invested over $66 million into development for drisapersen, including $16.4 million in the first three months of 2016.
Trouble began last fall, when an FDA advisory panel criticized the evidence backing up the drug. The FDA subsequently rejected the drug in January.
BioMarin's last hope for drisapersen was in Europe, where it was still under regulatory review. But a May meeting with the key Committee for Medicinal Products for Human Use (CHMP) "clearly indicated" the panel would recommend rejection, the company reported Tuesday.
"The withdrawal of the [application] and discontinuation of our current experimental drugs for Duchenne is a difficult but necessary decision at this time," said BioMarin CEO Jean-Jacques Bienaimé.
The decision, while expected, is still a another heavy blow to DMD patients and families. In the U.S., drisapersen's rejection was followed by a rejection of another DMD drug from PTC Therapeutics.
A third, Sarepta's eteplirsen, is still under review after the FDA delayed a final decision originally set for last week. But a panel of independent experts has criticized the methodology of Sarepta's trial supporting eteplirsen, and voted in April against recommending approval.
Patients and advocates made an impassioned case in favor of eteplirsen at that April meeting, arguing clinical evidence from Sarepta's small trial showed proof of efficacy. Rejection from the FDA still looks likely although the delay gave some hope for approval and sent Sarepta shares higher. Eteplirsen represents the last near-term hope for a DMD treatment, particularly after the termination of BioMarin's program.
"BioMarin did everything possible to bring this treatment to the Duchenne community. It’s very sad that both regulatory bodies, the FDA and EMA, did not see the benefit that so many boys have received from drisapersen," said the patient advocacy group Cure Duchenne in a statement on BioMarin's decision.
Ending the program could result in a write-down of "all or a significant portion" of the costs related to BioMarin's acquisition of Prosensa. The company already recognized a nearly $200 million impairment charge to IPR&D assets tied to drisapersen in the fourth quarter of last year.
Although revenues climbed nearly 17% in the first quarter compared to a year prior, BioMarin posted a net operating loss of $81 million. BioMarin expects to hit non-GAAP break-even or better by 2017.
And it seems BioMarin won't give up on DMD completely. Bienaimé said the company would push forward with "next generation oligonucleotides" in hopes of developing another treatment.