Risdiplam, Oral SMA Treatment, Up for Approval in Japan

Chugai Pharmaceutical, part of the Roche Group, is asking that risdiplam be approved as a daily oral treatment for spinal muscular atrophy (SMA) patients in Japan.

A new drug application seeking approval, submitted to that country’s Ministry of Health, Labour and Welfare (MHLW), may be given priority review in Japan, where risdiplam was designated an orphan drug in 2019.

“We will work to obtain the regulatory approval for risdiplam to provide this new oral therapy for people with SMA as soon as possible,” Osamu Okuda, president and chief operating officer of Chugai, said in a press release.

Risdiplam is a small molecule that works to increase the production of the survival motor neuron (SMN) protein, a protein essential for muscle health, and lacking in SMA patients. The medication boosts the ability of SMN2 — a gene similar to SMN1 that normally remains unaffected in this disease but can also provide instructions to make SMN — to produce the protein.

Risdiplam is approved to treat patients ages 2 months and older with all SMA types in the U.S., where it is marketed under the brand name Evrysdi by Roche and Genentech (also part of Roche). These companies developed the liquid treatment, available for at-home use, in collaboration with PTC Therapeutics and the SMA Foundation.

Evrysdi is under regulatory review in Europe for possible approval, and under review in Brazil, Chile, China, Indonesia, Russia, South Korea, and Taiwan. The company’s release did not state if that brand name will also be used in Japan.

Chugai’s application is supported by data from two Roche-sponsored clinical trials: FIREFISH (NCT02913482) and SUNFISH (NCT02908685).

FIREFISH, an open-label Phase 2/3 trial, is currently evaluating the safety, tolerability, efficacy, and pharmacological properties of risdiplam in infants, enrolled at ages 1 to 7 months, with type 1 SMA.

The study met its primary goal, with 29% of enrolled infants able to sit without support for five seconds — a motor milestone not seen in untreated infants with this form of SMA — after one year of treatment. Most of its 41 treated children were alive at one year, able to swallow and breathe, and showed clinically meaningful improvements in motor function.

SUNFISH, also a Phase 2/3 trial, is assessing the safety, tolerability, and efficacy of risdiplam against a placebo in people with type 2 or type 3 SMA, ages 2 to 25.

One-year data from this study’s second part showed that, compared with a placebo, risdiplam’s use significantly improved or stabilized motor abilities in 180 non-ambulatory patients. Greater motor gains, as expected, were seen in those treated at younger ages.

Two-year data from an exploratory efficacy analysis of SUNFISH also indicated risdiplam’s use led to significant improvements in motor skills, compared with untreated patients participating in natural history studies.

Risdiplam was generally safe and well tolerated in both trials. Common side effects associated with the medication included common cold symptoms, fever, and headache.

“As potentially the first oral drug for SMA, risdiplam demonstrated clinically meaningful treatment effects across infants and adults in two clinical studies for Types 1, 2 and 3 SMA. I believe that risdiplam will make a significant contribution to the treatment of SMA with its proven efficacy,” Okuda said.