The U.S. Food and Drug Administration (FDA) approved another therapy for Duchenne muscular dystrophy (DMD), this time NS Pharma’s Viltepso (viltolarsen). NS Pharma is a wholly owned subsidiary of Nippon Shinyaku Co.
DMD is a muscle-wasting disease caused by mutations in the dystrophin gene. It is a progressive disease that usually causes death in early adulthood, with serious complications that include heart or respiratory-related problems. It mostly affects boys, about 1 in every 3,500 or 5,000 male children.
It is caused by several different mutations to the dystrophin gene, which codes for muscle. Viltepso was approved for patients with DMD amenable to exon 53 skipping.
“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,” said Vamshi Rao, Ann & Robert H. Lurie Children’s Hospital of Chicago, who led the Phase II study the New Drug Application was built on. “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.”
The Phase II trial was a two-period study in DMD patients aged four to less than 10 years of age conducted in North America, and a multicenter, open-label trial in boys five to less than 18 years of age run in Japan. In Study 1, of the patients who received the recommended dose of 80 mg/kg/wk, 100% showed an increase in dystrophin levels and 88% showed dystrophin levels of 3% or greater than normal. The mean increase in dystrophin expression after 20 to 24 weeks of treatment was almost 6% of normal compared to 0.6% at baseline.
In a statement, the FDA said, “The FDA concluded that the applicant’s data demonstrated an increase in dystrophin production that is reasonably likely to predict clinical benefit in patients with DMD who have a confirmed mutation of the dystrophin gene amenable to exon 53 skipping. A clinical benefit of the drug has not been established. In making this decision, the FDA considered the potential risks associated with the drug, the life-threatening and debilitating nature of the disease, and the lack of available therapies.”
As part of the accelerated approval process, the FDA is requiring NS Pharma to run a clinical trial to confirm clinical benefit of the drug. It will evaluate whether the drug improves the time to stand for DMD patients with this particular mutation. If it doesn’t show clinical benefit, the agency may withdraw approval.
Common side effects of the drug were upper respiratory tract infection, injection site reaction, cough and fever. Although kidney toxicity wasn’t observed, the FDA notes that clinical experience with the drug is limited and kidney function should be monitored in patients receiving Viltepso.
The FDA approved Sarepta’s Vyondys 53 (golodirsen) for this same indication and mutation in December 2019. In August 2019, the agency issued a Complete Response Letter (CRL) over the risk of infections at intravenous infusion ports and renal toxicity observed in preclinical models. Sarepta also has another DMD drug, Exondys 51, which is for patients with a confirmed mutation amenable to exon 51 skipping.
Viltepso requires a weekly 60-minute infusion. The patients can receive it either at home or in a healthcare facility.
The original approval for a DMD drug, for Exondys 51 in 2016, was highly controversial. There were at least three major opponents to approval within the FDA at the time. Ronald Farkas, clinical team leader, left the agency just prior to approval. The agency’s acting chief scientist, Luciana Borio, and Ellis Unger, director of the office of drug evaluation, strongly opposed approval, arguing that Sarepta did not provide substantial evidence of Exondys 51’s effectiveness. But Janet Woodcock, director of the CDER, pushed it through, overruling her staff. The final decision then went to then FDA Commissioner Robert Califf. Califf reportedly had similar reservations as Borio and Unger, but sided with Woodcock.
Like with NS Pharma, Sarepta’s drugs for DMD were approved with a requirement of running confirmatory trials. However, the company has yet to provide that evidence. The trials are recruiting patients and expected to provide results in the next few years.
Meanwhile, Sarepta’s Exondys 51 and Vyondys 53 have similar prices, about $300,000 per year for patients who weight about 44 pounds. NS Pharma has yet to disclose a price for Viltepso.