Prosensa Looks To Take DMD Programs Forward; Remains Hopeful For Drisapersen

Prosensa Looks To Take DMD Programs Forward; Remains Hopeful For Drisapersen

ByJoseph Haas / Email the Author / View Full Issue
Word Count: 963 / Article # 14140114005 / Posted: January 14 2014 6:05 PM

Executive Summary

CEO Schikan notes that despite GSK’s exit from drisapersen collaboration, the four-plus year partnership left his firm with the largest clinical database in the rare disorder. Next step is meeting with stakeholders to find a regulatory path forward for the Phase III exon-skipping compound.

Few observers were surprised when GlaxoSmithKline PLC decided to terminate its Duchenne muscular dystrophy (DMD) partnership with Prosensa Holding BV Jan. 13, but the Dutch biotech is making clear that it hopes to continue developing drisapersen, an RNA antisense oligonucleotide exon-skipping compound, on its own, as well as the rest of its portfolio of DMD candidates.

In theory, drisapersen and Prosensa’s other candidates, three of which have reached mid-stage clinical development, address the underlying cause of DMD with exon-skipping technology that restores the expression of dystrophin protein. The rare muscle-wasting disease is caused by mutations that arise in certain exons during the transition of the gene that codes for the dystrophin protein, causing it to function improperly or not at all ("DMD Development Landscape Shifts After Prosensa Failure; Sarepta Continues Strong" — "The Pink Sheet," Oct. 7, 2013).

GSK paid $25 million upfront, with the potential for up to $665 million in milestones, in October 2009 for exclusive worldwide rights to drisapersen, as well as options on three other exon-skipping candidates [See Deal]. Although the antisense compound demonstrated efficacy, as measured by improvement in the six-minute walk test (6MWT) in two other placebo-controlled trials, the two companies announced Sept. 20 that drisapersen failed to meet its primary efficacy endpoint in the Phase III DEMAND III study.

GSK announced it was exiting the partnership on Jan. 13, with Prosensa issuing a release noting that it now has unencumbered ownership of its entire DMD portfolio. In an interview, Prosensa CEO Hans Schikan did not specify whether Prosensa paid GSK anything to re-acquire its intellectual property rights, including the options GSK had held, but said the multinational pharma holds no downstream rights for any of the DMD candidates.

Schikan also would not be pinned down on whether Prosensa will seek another co-development partner for drisapersen. The first order of business is to meet with stakeholders, including patients, clinicians, patient advocacy organizations and regulators, to see if there is a regulatory path forward for the compound, he said. Prosensa plans a presentation Jan. 16 at the J.P. Morgan Healthcare Conference in San Francisco, and a separate update for the DMD community on Jan. 21.

Prosensa earned at least $28 million in milestones under the collaboration with GSK, but Schikan said that cash was secondary in importance to the role GSK played in advancing drisapersen. Last September’s setback meant that competitor Sarepta Therapeutics Inc. might move into the lead in developing the first DMD drug to reach market, with its eteplirsen, also an exon-skipping compound. Prosensa and Sarepta currently are tied up in a patent dispute over European rights to exon-skipping technology.

“After this collaboration with GSK, and thanks to their commitment, we now have the largest database in DMD, which is still an unmet medical need,” Schikan said. “We at Prosensa probably never would have been in a position to develop this compound in this way. More than 300 patients have been treated in various clinical trials – three placebo-controlled studies and two open-label studies.”

Prosensa and GSK have agreed to share some of the data from those trials with the scientific community to advance overall understanding of DMD. The biotech also will continue a 250-patient study to develop a natural history of the disease that was begun as part of the collaboration, Schikan said.

Asked if drisapersen might have gotten lost in the R&D shuffle at a big pharma company, Schikan said GSK had dedicated the needed attention to drisapersen, but said that now it might be a better time for a company focused on rare diseases and DMD to take the program forward. “We won’t leave any stone unturned if there is a way to help patients with DMD,” he said.

Pooled Data Analysis Ongoing

In the aftermath of the DEMAND III data, the companies indicated they would study the database in hopes of identifying a sub-population in which the data could be shown as efficacious, perhaps when pooled with data from the successful DEMAND II and DEMAND V studies. Those reviews are ongoing, Schikan said. At the time of the trial failure, he had noted that DEMAND III treated patients with a more advanced disease state. In the previous two trials, patients had been required to be able to lift themselves up from the floor in seven seconds – that requirement was not enforced for participation in DEMAND III.

In a Jan. 13 note, Leerink analyst Joseph Schwartz maintained an “outperform” rating on Prosensa’s stock, but admitted GSK’s departure indicated that the sub-group and pooled data reviews had not succeeded. “While the data were not included in the press release, we believe that GSK’s strategic decision suggests that the post-hoc analyses did not show signs of efficacy sufficient to garner drisapersen regulatory approval,” he wrote.

Schwartz estimated that Prosensa had about $98 million cash on hand at the end of 2013, providing sufficient runway into mid or late 2015. The best approach forward with drisapersen, he said, might be yet another trial, which if successful could be pooled with the DEMAND II and V datasets to obtain FDA approval. Drisapersen has orphan drug status in the U.S. and EU and also was selected by FDA as a breakthrough therapy in 2013.

By skipping exon 51, drisapersen would treat about 13% of the DMD patient base, according to Prosensa. Its other DMD candidates, PRO045, PRO046 and PRO053, each would skip one specific exon implicated in the disease and would address 6%, 8% and 8% of the patient population, respectively, Schikan explained. Each currently is in Phase I/II of development.

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