All Eyes Turn to Sarepta as BioMarin Shutters Its Kyndrisa Duchenne Program

All Eyes Turn to Sarepta as BioMarin Shutters Its Kyndrisa Duchenne Program June 1, 2016
By Mark Terry, Breaking News Staff

San Rafael, California-based BioMarin Pharmaceutical announced today that it is abandoning its Kyndrisa (drisapersen) program for Duchenne muscular dystrophy (DMD).

In January, the U.S. Food and Drug Administration (FDA) rejected the company’s application for Kyndrisa. In November 2015, 15 of 17 members of the FDA’s Peripheral and Central Nervous System Drugs Advisory Committee indicated they felt BioMarin’s late-stage study lacked statistical significance.

Of the three trials the company ran on Kyndrisa, two did not meet their statistical endpoint, which was getting patients taking the drug to walk farther in six months. This is a standard assessment for drugs being tested for similar diseases.

DMD is a muscle wasting disease caused by mutations in the dystrophin gene. The mutations result in a lack of production of the dystrophin gene. The disease is progressive and typically causes death in early adulthood, with serious complications that include heart or respiratory-related problems. It mostly affects boys, about 1 in every 3,500 to 5,000 male children.

The drug was still being evaluated by the European Medicines Agency (EMA), but part of BioMarin’s announcement today was the company’s withdrawal of its Marketing Authorization Application (MAA) in Europe. The company, based on its talks with the FDA and the FDA’s Complete Response Letter (CRL), plans to fold the Kyndrisa program in addition to three other first-generation follow-on products, BMN 044, BMN 045 and BMN 053, which are currently in Phase II trials for specific types of DMD.

“The withdrawal of the MAA and discontinuation of our current experimental drugs for Duchenne is a difficult but necessary decision at this time,” said Jean-Jacques Bienaimé, chairman and chief executive officer of BioMarin, in a statement. “We want to extend our sincere gratitude to all of the families and caregivers who supported our efforts over the last year to bring Kyndrisa to patients with Duchenne. Our plan now is to invest in research of next generation oligonucleotides with the goal of making a safe and effective treatment available for boys with this devastating disorder.”

BioMarin acquired Kyndrisa when it bought Prosensa of Leiden, Netherlands, in November 2014 for $680 million. In addition to the cash, there were two $80 million milestone payments related to regulatory approvals in the U.S. and Europe, which Prosensa shareholders will now not receive.

BioMarin’s abandonment of Kyndrisa once again puts the focus on Sarepta Therapeutics . That company’s DMD drug, eteplirsen, has been on a very dramatic roller-coaster ride. Its FDA review was postponed in January until April due to a pending snowstorm on the East Coast. In February, 109 members of Congress sent a letter to the FDA urging it to accelerate approval of a DMD drug, not specifying any drug, but suggesting it should approve any treatment, and soon.

In March, 36 DMD experts signed a letter to the FDA urging approval of Sarepta’s eteplirsen. It was written by Carrie Miceli and Stanley Nelson, co-directors of the Center for Duchenne Muscular Dystrophy at UCLA.

In April, the FDA held a hearing that was a bit of a media circus. It went on for 12 hours and had 52 public commentators, often offering emotional cries for help, including several boys with DMD and their parents. The final decision was to be made on May 26, but on May 25 the FDA and Sarepta announced that the FDA was going to miss the deadline because “they are continuing their review and internal discussions related to our pending NDA for eteplirsen.”

Some people feel that BioMarin’s announcement today will place some pressure on the FDA to approve Sarepta’s eteplirsen.

“There’s only one standing now,” said Christine McSherry, executive director of the Kingston, Massachusetts-based Jett Foundation, to the San Francisco Business Times. McSherry is also the mother of a 20-year-old Duchenne patient, Jett, who was involved in clinical trials of both drugs. “There would seem to be some sideways pressure (on the FDA) to approve” eteplirsen.

Jett McSherry received three doses of drisapersen, but had a reaction at the injection site. Upon receiving Sarepta’s eteplirsen, he was stable after nine weeks and, according to Christine McSherry, he recovered some fine motor skills. “Honestly,” she told The San Francisco Business Times, “I think the drug saved his life.”

BioMarin has indicated that it still expects its 2017 adjusted profit to break even at the very least, but had previously indicated that it might need to write off all or most of the costs tied to the Prosensa acquisition. The company has also indicated the change may result in layoffs, although how many, when and where has not been indicated.

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