BioMarin Gets Unfavorable View From Panel on Duchenne Drug

  • Panel voted failed final-phase trial weakens earlier studies
  • Sarepta is developing a related drug for the rare disease

BioMarin Pharmaceutical Inc.’s experimental drug for Duchenne muscular dystrophy got an unfavorable review from U.S. regulatory advisers, possibly hurting its chances of becoming the first therapy on the market for the genetic disease that affects mainly young boys.

A panel of outside Food and Drug Administration advisers voted at a meeting Tuesday that inconsistencies in clinical trials of the drug weakened BioMarin’s argument that the treatment would work.

The FDA is scheduled to decide whether to approve Kyndrisa, also known as drisapersen, by Dec. 27. BioMarin shares have been halted throughout the day. The stock had risen 14 percent in the last 12 months through Monday.

Sarepta Therapeutics Inc. is working on a similar drug that the agency will decide whether to approve by Feb. 26. Sarepta shares gained less than 1 percent Tuesday to $37.32. PTC Therapeutics is working on a drug for Duchenne muscular dystrophy as well that it hopes to submit for approval by the end of the year.

Two of the three clinical trials that BioMarin relied on to try to persuade the FDA to approve Kyndrisa failed to meet their main goal, which was to help patients taking the drug to walk farther in six minutes -- a standard assessment used in treatments for similar diseases.

Totality of Data

BioMarin has argued that while the trial results may not have been perfectly consistent, the data taken as a whole argues in favor of the drug. At the panel, 15 of 17 eligible members voted that the failure of the largest trial to meet its primary goal weakened any positive effects seen in smaller, earlier trials. Two panel members voted the issues had no effect.

BioMarin’s largest trial was a final-phase study that included 186 boys with the disease and that panelists felt best portrayed how the drug would work in the real world. Drugs are typically tested in three stages before being submitted to the FDA.

Duchenne muscular dystrophy is a progressive disease in which the body lacks a protein, called dystrophin, that keeps muscles intact. It strikes in childhood, and patients typically end up in wheelchairs. Many die by age 25 from lung disorders, according to the National Institutes of Health.

Kyndrisa is supposed to raise dystrophin levels, but the trials also failed to show a noticeable increase in the protein in patients on the drug.

Wishful Thinking?

Patients and families told heart-wrenching stories during the meeting about improvements the drug made in their lives during clinical trials, from being able to shower themselves and climb stairs to riding bikes and even roughhousing with their brothers.

“This simply cannot be wishful thinking or placebo effect,” one of the mothers said.

It’s tough to reconcile the families’ testimonies with the data that show the drug isn’t yet ready, said Chiadi Onyike, a panelist and professor of psychiatry and behavioral sciences at Johns Hopkins University School of Medicine in Baltimore.

“I think there are suggestions that it could be beneficial for some individuals,” said Michelle Mielke, associate professor in the Department of Health Sciences Research at the Mayo Clinic in Rochester, Minnesota.

Mielke said the “some” still must be determined.

Christopher Cassidy, a patient representative on the panel with Duchenne muscular dystrophy, even expressed concerns with BioMarin’s data and voted that it weakened earlier study results as well.

Sales Estimates

Analysts lowered their estimates for how much revenue Kyndrisa would generate to $332 million in 2018, from an earlier average projection of $402.5 million, after FDA staff released their briefing on the drug on Friday.

In clinical trials of about 300 people, patients experienced blood platelet levels low enough that they could cause serious bleeding complications, kidney toxicity and injection site reactions including ulceration, irreversible scaring and atrophy, the FDA staff said. If the drug is approved, FDA staff recommended a boxed warning on the drug’s label, describing the side effects, and laboratory monitoring for blood platelet levels and kidney toxicity.

Kyndrisa is designed to fix a mutation in patients’ genetic code, in effect “skipping” the mutation to help the body produce dystrophin.

Henry Fuchs, chief medical officer at BioMarin, explained how the drug works by using the image of wooden toy train tracks that click together with male and female ends. Patients with Duchenne muscular dystrophy are missing a part of the track, so pieces of the same gender are touching and the train gets stuck. Kyndrisa “skips” the broken piece as well as the next one so the track lines up properly.

About 2,300 patients in the U.S. would be eligible for the treatment, BioMarin said during the meeting.

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