November 25, 2015
By Mark Terry, BioSpace.com Breaking News Staff
The U.S. Food and Drug Administration (FDA) Peripheral and Central Nervous System Drugs Advisory Committee met yesterday to discuss BioMarin ’s Kyndrisa (drisapersen) for Duchenne muscular dystrophy (DMD) and it was not pretty.
The committee, which doesn’t vote officially, but provides recommendations for an approval vote to be made on Dec. 27, nonetheless had 15 out of 17 members saying the company’s late-stage study lacked statistical significance. There has been some criticism of the advisory committee 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.”
Also of concern was that the panel discussion had the focus on families of or patients with DMD who were on the drug, as opposed to an emphasis on presenting supporting data. Feuerstein in particular notes that when the discussion would shift toward possible BioMarin approval, the FDA’s lead reviewer on drisapersen, Ron Farkas, would shoot it down, at one point saying “he believed the drug would kill Duchenne patients if used widely.”
DMD is a muscle wasting disease caused by mutations in the dystrophin gene. As a result of the mutations, the dystrophin protein is not produced. The disease is progressive and typically results in 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 essentially skips over the missing gene segment and “patches” another area, allowing the gene to produce dystrophin. However, there is some question as to the quality of the dystrophin produced, and whether the amount produced is adequate.
Analysts are all over the place in how they interpreted yesterday’s meeting. “I don’t think they (BioMarin) will necessarily be able to convince the FDA staff to change their mind,” said Heather Behanna, an analyst with Wedbush Securities.
Feuerstein himself gives the company a 5 percent shot of winning approval, and thinks his number may be optimistic. Feuerstein also takes aim at some of his fellow analysts, including Piper Jaffray’s Josh Schimmer, who gives approval odds of 65 percent, saying, “I like Schimmer personally but he’s insane.”
Michael Yee, with RBC Capital, gives his approval odds at 50 to 60 percent, and Evercore ISI’s Mark Schoenebaum and Barclay’s Geoff Meacham give a 50-50 roll of the dice. Alternately, Brian Skorney, with Baird, doesn’t think the drug stands any chance of being approved.
It also seems understandable, and rather sad, that parents of the boys with the disease who spoke at the panel indicated they believed in the drug, even if the clinical data doesn’t seem to support it. Most patients with DMD die around age 25 and usually before age 30.
“This simply cannot be wishful thinking or placebo effect,” one of the mothers testified.
Farkas, for his part, pointed out at the meeting that DMD patients often stabilize or improve before progression of the disease continues. And although BioMarin was arguing that the drug was causing the improvement, the clinical trials data “were indistinguishable from the natural history of Duchenne progress,” reported Feuerstein.
BioMarin sales were halted yesterday because of the meeting. Prior to the halt, shares traded for $97.80. They had tumbled 5 percent last week after a previous panel’s review.
Analysts typically believe BioMarin is quite strong, despite this setback, with a deep pipeline for rare drugs like achondroplasia, Batten disease and Pompe disease.
Sarepta Therapeutics has its own treatment for DMD, eteplirsen. The FDA panel will evaluate it on Jan. 22, 2016. It has shown positive results in a very small trial of 12 patients and seems to have fewer side effects than BioMarin’s drug. The company is expected to make a similar argument comparing the drug’s effects against the natural history studies of DMD patients.
