FDA clears Phase 2 study of exon skipping therapy for DMD

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by Patricia Inácio, PhD |

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Having reached an agreement with the U.S. Food and Drug Administration (FDA), NS Pharma will be launching a Phase 2 clinical trial to evaluate its investigational exon 44 skipping therapy for Duchenne muscular dystrophy (DMD).

Trial details will be forthcoming once enrollment is imminent, according to NS Pharma, but the study’s goal is set: to assess the efficacy of the company’s treatment candidate NS-089/NCNP-02 for DMD.

To that end, the study will measure changes in the levels of dystrophin — a protein essential for muscle health — and motor function among participants.

“We are pleased to announce FDA’s clearance to proceed with our Phase [2] clinical trial in our endeavor to help patients with Duchenne amenable to exon 44 skipping therapy,” Takeshi Seita, vice president of R&D at NS Pharma, said in a press release.

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More details to come on trial of NS-089/NCNP-02

According to Vamshi Rao, MD, an attending physician at the Ann & Robert H. Lurie Children’s Hospital of Chicago, there are “no available antisense treatments that target Duchenne patients amenable to exon 44 skipping therapy.”

“Progress has been made in the treatment of Duchenne, but patients and families need new and more treatment options,” Rao said, adding that he’s “excited about this program and the potential advance of effective treatments for Duchenne muscular dystrophy.”

A Phase 1/2 trial of NS-089/NCNP-02 (NCT04129294), conducted in Japan and completed in May 2022, measured changes in dystrophin levels and motor function in six DMD patients, all male. The boys were infused with either 40 mg/kg (low dose) or 80 mg/kg (high dose) of the therapy, each given weekly for 24 weeks, or about six months.

The results showed that dystrophin protein levels increased to a mean of 10.27% of normal in patients treated with the low dose, and to 15.79% of normal in those treated with the high dose.

Motor function was either maintained or showed a trend for improvements, as assessed by the North Star Ambulatory Assessment score. No treatment discontinuations due to side effects were registered.

The six participants have joined the study’s extension Phase 2 part (NCT05135663), which will continue to assess the safety, tolerability and efficacy of the low and high doses of NS-089/NCNP-02, infused every week for about four years (216 weeks). The study is expected to be completed in July 2026.

“We are confident in our exon skipping drug discovery platform and excited about the future potential of our development program,” Seita said.

In Duchenne, a mutation in the DMD gene disrupts the production of dystrophin. Most DMD-causing mutations lead to one or more exons — the sections that code for the protein — being deleted from the gene sequence. That, in turn, makes the genetic code after the mutation fall out of alignment. As a result, cells end up producing a shorter protein that is rapidly degraded.

Dystrophin production can be restored by skipping certain exons, allowing the rest of the gene to be properly read. NS-089/NCNP-02 is an exon-skipping therapy designed to essentially jump over exon 44 of the DMD gene, to produce a shorter than normal, yet functional version of the dystrophin protein.

The therapy may benefit 7% to 11% DMD patients amenable to exon 44 skipping.

We are confident in our exon skipping drug discovery platform and excited about the future potential of our development program.

NS Pharma‘s Viltepso (viltolarsen) is approved in Japan and conditionally approved in the U.S. for people with DMD amenable to exon 53 skipping. A Phase 3 trial called RACER53 (NCT04060199) is underway to further evaluate Viltepso’s safety and effectiveness in these patients.

Nippon Shinyaku, NS Pharma’s parent company, has other investigational exon skipping therapies in preclinical development.

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