January 15, 2016
By Mark Terry, BioSpace.com Breaking News Staff
The U.S. Food and Drug Administration (FDA) announced yesterday that it did not approve San Rafael, Calif.-based BioMarin Pharmaceutical Inc. ’s application for Kyndrisa (drisapersen). Kyndrisa was being tested for treatment for Duchenne muscular dystrophy (DMD).
In November 2015, the FDA’s Peripheral and Central Nervous System Drugs Advisory Committee met to discuss the drug and at that time, 15 out of 17 members said they felt BioMarin‘s late-stage study lacked statistical significance. There was some controversy over that meeting, with The Street’s Adam Feuerstein describing the panel’s discussions as “often convoluted and off-target, as if they really didn’t understand the drug or Duchenne muscular dystrophy.”
DMD is a muscle wasting disease caused by mutations in the dystrophin gene. Those mutations result in a lack of production of the dystrophin protein. 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.
Kyndrisa is still under review in the European Union. Meanwhile, BioMarin is reviewing the FDA Complete Response Letter and plans to work with the FDA on what its next steps might be.
This rejection not only shifts some attention to competitor Sarepta Therapeutics Inc. ‘s efforts to get approval for its own drug for DMD, but on the nature of drug research and approvals for rare diseases. As BloombergBusiness writes, “Pharmaceutical companies are willing to go to great lengths to create medicine for rare diseases because they can charge hundreds of thousands of dollars per patient.”
The FDA argued that Kyndrisa didn’t show enough benefit. Of the three trials BioMarin ran, two didn’t meet their primary endpoint, which was getting patients taking the drug to walk farther in six minutes. This is a standard assessment for drugs being tested for similar diseases.
In addition, Kyndrisa’s adverse side effects were serious—low platelet levels that could lead to serious bleeding problems, kidney toxicity, and ulceration, scarring and atrophy at the injection sites.
The November meeting was marked by sad and often harrowing stories by patients and parents of patients with DMD. The BloombergBusiness article has a somewhat disconcerting statement: “Advocates working to get treatment on the market for DMD, which affects about 1 in every 3,500 to 6,000 boys born each year in the U.S., will focus their efforts on getting the FDA to allow patients and families to decide for themselves if the medicine is worth any potential risks.”
It’s a concept that completely undermines the reason for drug regulation and review. Families and patients often have the choice of declining any treatment, but there are legitimate safety reasons for determining drug approval, as well as efficacy reasons—why approve a drug if the science indicates it is ineffective and potentially dangerous?
“This is a relentlessly progressive disease, with no ebbs and flows,” said Debra Miller, founder and chief executive officer of CureDuchenne, to BloombergBusiness. “We know what happens with no drug. The boys all die.”
Originally scheduled for review on Jan. 22, 2016 by the FDA, Sarepta Therapeutics’ eteplirsen for DMD was turned down today by the FDA as well. Eteplirsen takes a different mechanism to treating DMD and has shown positive results in a very small trial of 12 patients. It also has shown fewer side effects than Kyndrisa.
As reported by The Wall Street Journal, the technical journal Annals of Neurology published the results of a midstage trial of eteplirsen that indicated a “slower rate of disease progression after three years of use.”
Although analysts generally feel that Sarepta’s drug had a better chance of being approved, the primary strike against it was the trial size. A trial with only 12 patients is very small. “It’s a different leap of faith you have to take with Sarepta,” Ira Loss, an analyst with Washington Analysis, told BloombergBusiness. “They do have patients who are still walking around after three years. The risk is you don’t have a lot of patients.”
BioMarin has taken a hit over the last year. Shares traded on July 20, 2015 for $149.13, plunged to $96.82 on Sept. 29, recovered to $117.04 on Oct. 30, then plunged again to $96.65 by Dec. 10. They shot up again to $106.07 on Dec. 29, but are currently trading for $82.23.
Sarepta is also suffering . Shares traded on Oct. 5, 2015 for $41.79, dropped to $42.98 on Oct. 23, rose to $38.67 on Dec. 30, and fell off a cliff recently, and is currently trading for $13.48.
