FDA Approves Viltolarsen, Now Viltepso, for DMD Patients With Exon 53 Mutation

The U.S. Food and Drug Administration (FDA) has conditionally approved NS Pharma‘s Viltepso (viltolarsen) for people with Duchenne muscular dystrophy (DMD) amenable to exon 53 skipping. 

Viltepso is given via intravenous (into-the-vein) administration at a dose of 80 mg/kg of body weight. Eligible patients can choose to receive the weekly hourlong infusion, done by a trained healthcare professional, at home, at a treatment center, or in a hospital. 

NS Pharma, the U.S. subsidiary of Nippon Shinyaku will provide individualized resources to families, physicians, and healthcare professionals through the NS Support program, and will host a series of webinars on the coordination of care. Webinar information and registration will be announced on Twitter and LinkedIn.

“The approval of Viltepso is an exciting development for DMD patients amenable to exon 53 skipping therapy and may rapidly become a foundational treatment for these patients,” Vamshi Rao, MD, an investigator in Viltepso’s clinical program from Ann & Robert H. Lurie Children’s Hospital of Chicago, said in a press release.

Viltepso had already been approved in Japan and was available in the U.S. for eligible patients under an expanded access program.

“The FDA is committed to fostering drug development for serious neurological disorders like Duchenne muscular dystrophy,” Billy Dunn, MD, director of the Office of Neuroscience in the FDA’s Center for Drug Evaluation and Research, said in a separate press release. “Today’s approval of Viltepso provides an important treatment option for Duchenne muscular dystrophy patients with this confirmed mutation.”

As part of the accelerated approval process, the FDA will require the company to confirm Viltepso’s clinical benefit in the Phase 3 RACER53 trial (NCT04060199). If the trial fails to confirm clinical benefit, the FDA may withdraw Viltepso’s approval, the agency said.

RACER53 is currently enrolling approximately 74 boys, ages 4 to 7, in several countries, including the U.S., Japan, Canada, and Europe. Information on clinical sites and contacts can be found here.

Participants will receive weekly 80 mg/kg doses of Viltepso or a placebo by intravenous infusion for up to 48 weeks. Measured outcomes include time to stand, time to run/walk 10 meters, the six-minute walking test, time to climb four steps, the North Star Ambulatory Assessment, and muscle strength assessed with a hand-held dynamometer.  

In approving Viltepso, the FDA considered the potential risks associated with the therapy, the life-threatening and debilitating nature of DMD, and the limited therapy options. The agency deemed NS Pharma’s data showing increased dystrophin production reasonably likely to predict clinical benefit in patients with a mutation amenable to skipping exon 53 of the DMD gene.

Dystrophin, a key protein to keep muscle cells together, is lacking in people with Duchenne. Viltepso is an exon-skipping therapy designed to “mask” exon 53 to produce a shorter but functional version of dystrophin. Nearly 8% of all DMD patients have mutations amenable to skipping this exon. (Exons are the DNA regions containing information to generate proteins.)

Viltepso’s approval was based on results of a Phase 2 trial (NCT02740972) conducted in North America, which included 16 boys, ages 4 to 9, with DMD amenable to exon 53 skipping who were able to walk. A second Phase 1/2 study (Japic CTI-163291), conducted in Japan, included 16 boys, ages 5 to 17.

In the North American-based study, all eight patients who received weekly 80 mg/kg doses of Viltepso showed an increase in dystrophin levels. Seven showed dystrophin levels of 3% or higher than normal. Overall, after 20 to 24 weeks of treatment, the mean level of dystrophin increased to nearly 6% of normal, in contrast to 0.6% at the study’s start.

“For decades, neurologists who treat DMD have hoped for the discovery of therapies capable of significantly improving dystrophin production, and the magnitude of dystrophin increases observed with Viltepso are impressive,” Rao said.

The most common side effects included upper respiratory tract infection, injection site reaction, fever, and cough.

While no patients experienced kidney toxicity during treatment, medications such as Viltepso may cause kidney damage. As such, a physician may want to monitor kidney health before and during treatment, according to NS Pharma.

“On behalf of NS Pharma and Nippon Shinyaku, I would like to express our deepest gratitude to the families and physicians who participated in our clinical trials and made today’s approval possible,” said Tsugio Tanaka, president of NS Pharma. “We are proud to now offer an important new treatment option to help address the significant unmet needs caused by this devastating disease.”

Viltepso is now the second treatment for DMD patients amenable to exon 53 skipping in the U.S., following last year’s FDA approval of Sarepta Therapeutics‘ Vyondys 53 (golodirsen).