Prosensa Provides Exon-Skipping Program Update to DMD Community

Biotech company Prosensa says an analysis of drisapersen trials in Duchenne muscular dystrophy and a DMD natural history study will guide future exon-skipping drug trials

Prosensa and GlaxoSmithKline hope to have a complete analysis of drisapersen clinical trials by the end of 2013, after which a future course can be charted.
Article Highlights:
  • Drisapersen, Prosensa's lead exon-skipping drug for DMD, recently showed disappointing results in a phase 3 trial conducted by Prosensa and its collaborator, GlaxoSmithKline.
  • Understanding these and other drisapersen trial results and analyzing data from a current study of the natural history of Duchenne MD will be used to guide Prosensa's future exon-skipping drug trials, the company said in a Nov. 18, 2013, conference call and press release.
  • Prosensa has three additional DMD exon-skipping drugs in clinical trials and two in laboratory-stage studies.
by Margaret Wahl on November 19, 2013 - 1:00pm

In a Nov. 18, 2013, press release and archived conference call, Dutch biotechnology company Prosensa updated the community about the status of its exon-skipping drug development program for Duchenne muscular dystrophy (DMD).

The update, which covers the third quarter of 2013, comes two months after Prosensa announced disappointing results for a phase 3 trial of drisapersen, an experimental DMD drug it is developing in collaboration with GlaxoSmithKline (GSK).

Prosensa's pipeline

Drisapersen, originally known as PRO051, is designed to change how cells interpret genetic instructions for the dystrophin protein by targeting exon (section) 51 of the dystrophin gene. The dystrophin protein is missing in DMD-affected muscles because of any of a large number of mutations in the dystrophin gene.

Prosensa has three additional exon-skipping drugs for DMD now in clinical trials and two in preclinical (laboratory) testing.

PRO044 (targeting exon 44), PRO045 (targeting exon 45), and PRO053 (targeting exon 53) are being tested in early-stage clinical trials. PRO052 (targeting exon 52) and PRO055 (targeting exon 55) are still undergoing laboratory development.

Drisapersen analysis expected by end 2013

"We remain committed to drisapersen," said Hans Schikan, CEO of Prosensa on the Nov. 18 conference call. "And we will continue to work with GSK on [drisapersen] and our overall program, as well as working with patient groups in the U.S. and Europe to provide as much information as possible."

Schikan said they are now analyzing the results of all studies of drisapersen and expect to have the analysis completed by the end of 2013.

He also said Prosensa and GSK are making progress in their current study of the natural history (usual course) of DMD, and that this study and the drisapersen analysis will inform their current and future drug studies. "The timing of other studies may be affected" by new data, he said.

Seeking responders

Unfortunately, the phase 3 drisapersen trial (conducted at some 50 sites outside the U.S.) showed that the distance a trial participant could walk in six minutes ("six-minute walk distance") was not significantly different in those treated with drisapersen for 48 weeks compared to those treated with a placebo.

On the conference call, Schikan said the companies will look at how factors such as a participant's age, baseline six-minute walk distance and serum creatine kinase level (an indicator of muscle damage) may have correlated with six-minute walk test results. In so doing, they hope to identify possible subgroups of boys with DMD (for example, perhaps those below a certain age) who may have benefited from treatment with drisapersen.

He noted that it would be premature to discuss these analyses at this point and that the path forward for drisapersen is not known at this time.

Modifications to newer studies possible

Giles Campion, Prosensa's chief medical officer, said the drisapesen analysis "will help us gain insights into how we may need to adapt — if at all — our follow-on programs."

Campion also said that laboratory studies have shown the five exon-skipping compounds developed by Prosensa after drisapersen are more effective than drisapersen at causing exon skipping in cells.

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