Muscular Dystrophy Drug Raises Superiority Issues In Breakthrough Path

Posted by: Christine McSherry on July 26, 2013

This blog post was sent to me by a fellow parent who has a son with Duchenne…interesting.


Muscular Dystrophy Drug Raises Superiority Issues In Breakthrough Path

FDA’s decision to grant a breakthrough designation to one of several Duchenne Muscular Dystrophy treatments in development could answer lingering questions on whether the new drug pathway could effectively force head-to-head superiority trials, as well as signal those circumstances in which FDA might rescind designations, sources said. An industry consultant said the simultaneous development of several DMD drugs presents a unique situation that could demonstrate whether the expedited approval of one drug could delay the development of others. FDA has said it has the discretion to grant multiple breakthrough designations for drugs with the same indication and rescind a designation should evidence show a product is not as effective as another available treatment.

Last month, FDA granted a breakthrough designation to GlaxoSmithKline’s drisapersen, an investigational treatment for patients with Duchenne Muscular Dystrophy (see FDA Week, June 28). An industry consultant said the designation could complicate the development pathway for other sponsors seeking approval for the same indication, who would be required to test their products against drisapersen if it receives approval. There are no approved therapies for DMD, but Serapta Therapeutics and Prosensa are also developing products to treat the disease.

“The question is if they offer fast track approval, are they going to force everyone that’s in trials right now to run head-to-head,” the consultant said. “If they run head-to-head, you could limit your options and there is not a history of FDA fast tracking three drugs with the same indication.”

The consultant called it an “oddball situation” that could make it more expensive to develop DMD drugs. It would not be beneficial to make development of these type of products more expensive, said the consultant, adding that muscular dystrophy patient groups would also likely want to ensure that all of the treatments were available.

An FDA spokeswoman said breakthrough designation requests could be granted to multiple products for the same indication, although the designations could also be rescinded if sponsors are unable to show their product is superior to other available therapies.

“If a product which has been granted a (breakthrough therapy designation) is subsequently approved, the FDA will evaluate other products granted a BTD for the same indication to see if all breakthrough criteria continue to be met,” the spokeswoman said. “If not, the FDA may rescind the BTD for those products which no longer offer substantial improvement over available therapy.”

The spokeswoman also said there will be no differences made between rare indications and indications that are not for rare diseases.

Breakthrough therapies are defined by the agency as those show high treatment effect early in clinical trials. FDA issued guidance last month on how companies could demonstrate their product was a substantial improvement over an available therapy, but also said determining whether a drug merited a breakthrough designation would be more challenging if an effective therapy was already available (see FDA Week, June 28).

A patient safety advocate agreed that there continues to be confusion about how the breakthrough pathway will affect drug development, but raised doubts about whether the availability of drisapersen would affect all DMD drugs in development since it will not treat all mutations of the disease.

“The problem with this particular drug is that it doesn’t target multiple mutations,” said Jane Larkindale, vice president of research for the Muscular Dystrophy Association. She said it is unlikely that drugs intended to treat different mutations of DMD would be required to prove superiority over GlaxoSmithKline’s product. If the company must show superiority, it could be more difficult to recruit patients, she said.

If there is already an available drug that patients know is effective, they will be less likely to want to participate in a trial where they could receive a placebo, she said. Companies that find themselves in that predicament would need to talk to FDA about the best pathway for their drug and ultimately decide if they feel their product is superior enough to an already marketed treatment to warrant further investment, Larkindale said.

She also said the Muscular Dystrophy Association has viewed the breakthrough pathway positively, but there are lingering questions about how the designations will affect drug development.

“We try very hard not to push for any for any one individual drug,” Larkindale said. “Our job is to get drugs for all of our patients. The situation where a good drug gets approval and an even better drug doesn’t, that does become a bit of a problem.”

Other groups have also pushed FDA to have patient advocates involved in identifying breakthrough drugs, saying patient advocates often come to the agency with more urgency than drug companies (see FDA Week, April 5).

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