Prosensa Will Pursue Accelerated Approval for Drisapersen to Treat DMD

The company plans to submit a New Drug Application to the U.S. Food and Drug Administration later this year, and has committed to conducting two confirmatory post-approval clinical trials

Biopharmaceutical company Prosensa outlined its plans to seek approval for drisapersen as a treatment for DMD in the United States and Europe in a June 3, 2014, press release and online presentation.
Article Highlights:
  • Dutch biopharmaceutical company Prosensa announced June 3 that it will apply to the U.S. Food and Drug Administration for accelerated approval of drisapersen in the United States for the treatment of Duchenne muscular dystrophy (DMD); the company also will pursue approval for the drug in Europe.
  • Drisapersen targets a section of the dystrophin gene called exon 51 and could provide treatment for 13 percent of the DMD population.
  • An accelerated approval designation allows patients to have access to a drug prior to full approval; Prosensa has committed to conducting two post-approval confirmatory studies aimed at getting full approval for drisapersen.
by Amy Madsen on June 6, 2014 - 9:56am

Dutch biopharmaceutical company Prosensa has outlined plans to seek accelerated approval in the United States for its experimental drug drisapersen, under development for the treatment of Duchenne muscular dystrophy (DMD). The company will seek approval for the drug in Europe as well.

Prosensa will file a New Drug Application (NDA) for drisapersen with the U.S. Food and Drug Administration (FDA) later this year, and has committed to conducting two post-approval confirmatory studies; an accelerated approval designation would allow patients to have access to the drug prior to full approval.

Drisapersen is an exon-skipping compound that targets a section of the dystrophin gene called exon (section) 51. It causes muscle cells to leave out (skip) that section of genetic instructions during the protein-making process and produce shortened but functional dystrophin protein molecules.

An estimated 13 percent of boys with DMD — those with dystrophin mutations near exon 51 — potentially can benefit from skipping exon 51.

“We’re very pleased with the positive response from the FDA and the pathway it has cleared toward accelerated approval of drisapersen to treat Duchenne muscular dystrophy,” said MDA Executive Vice President – Research, and Chief Medical and Scientific Officer Valerie Cwik. “MDA funded early-stage research into exon skipping as a therapeutic strategy, and the remarkable progress we’re seeing today with the development of drisapersen and similar experimental drugs is a direct result that we couldn’t be more proud of — and just one of the many ways MDA is working to save and improve the lives of people with muscle disease.”

Prosensa summarized its plans for regulatory approval for drisapersen in a June 3, 2014, press release and an online presentation, now archived on the company’s website.

Accelerated approval pathway is based on existing data

Prosensa’s plans to pursue accelerated approval for drisapersen are based on existing data for the drug and positive feedback from the FDA.

The company has been encouraged by the FDA to begin two confirmatory trials aimed at getting full approval for drisapersen as soon as possible. In a letter outlining approaches for the trials, the FDA suggested that:

  • A trial using a historical control group might be acceptable to confirm clinical benefit following accelerated approval; it would require that investigators confirm a large beneficial effect attributable to drisapersen that clearly leads to better outcomes in trial participants than would be expected in untreated boys.
  • Demonstration of a clear correlation between dystrophin protein production and a definitive clinical benefit, assessed on a six-minute walk test (distance walked in six minutes) or other measure in a randomized, placebo-controlled trial, could provide confirmatory evidence of drisapersen’s clinical benefit.

Clinical development of drisapersen

In addition to its two confirmatory trials of drisapersen, Prosensa plans to resume administering the drug to boys who have previously participated in clinical studies to test it.

Drisapersen has been tested in three double-blind, placebo-controlled trials, and two long-term open-label extension studies. For more, see DMD: What’s Next for Drisapersen?.

Prosensa currently has three other exon-skipping therapies (for exons 44, 45 and 53 of the dystrophin gene) in early-stage clinical trials and two other programs, targeting exons 52 and 55, in preclinical development. It is also conducting a study to better understand the natural history of DMD.

MDA's role in developing exon skipping

MDA has supported foundational work, including early laboratory development, of exon skipping since the 1990s. It continues to support the development and refinement of this strategy through grants to Steve Wilton at Murdoch (Australia) University; Judith van Deutekom, then at Leiden (Netherlands) University Medical Center, now at Prosensa; and others.

In addition, MDA’s Clinical Research Network studies of DMD disease progression in children under age 3 and in those who have lost the ability to walk are likely to provide crucial information for the future development of exon-skipping drugs and the design of clinical trials to test them.

To learn more about the experimental strategy, see Exon Skipping in DMD: What Is It and Whom Can It Help.

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