Sarepta Therapeutics has some company in the Duchenne muscular dystrophy field.
The FDA on Wednesday approved NS Pharma’s Viltepso (viltolarsen) for DMD patients with a mutation amenable to exon 53 skipping—the exact same population as Sarepta’s Vyondys 53.
And it's the same type of approval that landed Sarepta and the FDA in hot water before. Sarepta's FDA win for Vyondys 53 and sister med Exondys 51 fueled concerns because they were both based on a surrogate marker—the level of a protein called dystrophin. In both cases, Sarepta lacked evidence that the drugs could actually improve symptoms or fend off disease progression. The agency handed Viltepso an accelerated approval based on the same controversial endpoint.
DMD is a genetic disorder in which the patient cannot produce the dystrophin protein, which is crucial to muscle functions, leading to life-threatening complications. In Viltepso's case, approval was based on two small phase 2 studies showing treatment raised dystrophin levels by single-digit percentage points.
The two trials involved a total of 32 male patients. In one study, conducted in North America among boys aged 4 to less than 10 years of age, all eight patients treated with 80 mg/kg of Viltepso showed an increase in dystrophin levels. After 20 to 24 weeks of treatment, seven patients’ levels were at least 3% of normal. Average dystrophin expression reached 5.9% of normal, versus 0.6% before treatment. Boys on a lower dose ended the 20 to 24 weeks of treatment with a mean of 5.7%. Data from another 16-patient study in Japan were not available.
Viltepso's nod comes after a couple of dramatic turnabouts at the FDA for Sarepta's DMD drugs. The agency's own reviewers recommended against approval of Exondys 51, and an FDA panel of independent experts narrowly voted to reject the drug. But the agency approved it anyway, creating a dramatic scene where internal disagreement among FDA staffers led to some high-profile departures. Vyondys 53 was initially rejected, but after the company disputed the FDA's complete response letter, the agency actually changed its mind.
Viltepso helped patients create more dystrophin than Vyondys 53 did in their separate studies, though cross-trial comparisons have their known caveats. Patients on Vyondys 53 previously had 1.02% of normal dystrophin production after 48 weeks, up from 0.1% at base line. The two drugs’ change in dystrophin levels, at about tenfold, were similar across trials.
Doubters have been questioning whether—or exactly how much of—an increase in dystrophin can translate into actual improvement in symptoms. As is the case with Vyondys 53, the FDA said existing dystrophin data from Viltepso is “reasonably likely to predict clinical benefit” in DMD patients. Nevertheless, it also acknowledged that the benefit “has not been established.” That’s why NS Pharma is running the confirmatory phase 3 Racer53 trial to establish Viltepso’s efficacy profile and to turn the conditional FDA approval into a full one.
Those who will likely respond to exon 53-skipping therapy constitute about 8% of the DMD patient base. In the first half of 2020, Exondys 51 and Vyondys 53 together brought in sales of $211.8 million, an increase of $30.1 million over the same period last year.