Evrysdi for SMA Under Accelerated Review in Europe

The European Medicines Agency (EMA) has accepted and is now reviewing Roche’s marketing authorization application (MAA) requesting approval of Evrysdi (risdiplam) for treating spinal muscular atrophy (SMA).

Given that Evrysdi previously received the EMA’s priority medicines designation for SMA, enabling accelerated assessment of its application, a decision may be expected within 150 days, instead of the standard 210-day period.

“The acceptance of the MAA for Evrysdi marks an important milestone as we continue towards the goal of making this ground-breaking therapy available globally to a broad range of SMA patients,” Stuart W. Peltz, PhD, co-founder and CEO of PTC Therapeutics, said in a press release.

In 2011, Roche acquired an exclusive worldwide license to PTC’s SMA program. Evrysdi is the result of a collaboration between both companies, Genentech (a Roche subsidiary), and the SMA Foundation. Under the companies’ agreement, EMA’s acceptance to review the therapy triggers a $15 million payment to PTC from Roche.

“Evrysdi has consistently demonstrated clinically meaningful results in multiple clinical trials with a favorable safety profile. Evrysdi is an oral medicine that can be delivered and taken at-home, which is particularly important for SMA patients during the COVID-19 global pandemic,” Peltz said.

Besides the European Union, the therapy now is under regulatory review in seven countries, including Brazil, Chile, China, Indonesia, Russia, South Korea, and Taiwan.

EMA’s acceptance comes less than two weeks after the therapy was approved in the U.S. as the first oral and at-home daily treatment for all SMA types, ages 2 months and older.

Evrysdi is a small molecule that works to increase the levels of SMN — a protein essential for motor neuron and muscle health and lacking in people with SMA — in all cells of the body. It can be swallowed as a flavored liquid or given through a feeding tube once a day.

Evrysdi’s application was supported by positive top-line data from the ongoing Phase 2/3 FIREFISH (NCT02913482) and SUNFISH (NCT02908685) clinical trials and safety findings from the Phase 2 JEWELFISH study (NCT03032172).

Together, FIREFISH and SUNFISH are evaluating Evrysdi’s safety and effectiveness in a total of 221 people with SMA types 1, 2, and 3 from 1 month to 25 years old. Notably, SUNFISH involved type 2 or 3 patients, ages 2 to 25, making it the first placebo-controlled trial to include such a broad SMA patient group, by age and disability level.

Top-line data showed that both trials met their primary and most secondary goals, with one year of Evrysdi treatment resulting in significant improvements in motor milestones in infants with type 1 SMA, and in motor function in children and young adults with types 2 and 3 disease.

After one year of treatment, most of the 41 toddlers in FIREFISH’s Part 2 were alive, able to breathe and swallow, and achieved several motor milestones — “things that don’t happen in the natural history” of the disease, Paulo Fontoura, MD, PhD, said in an April interview with SMA News Today. Fontoura is Roche’s global head of neuroscience and rare disease clinical development.

While the greatest motor function improvements in SUNFISH were seen in the youngest age group (2–5 years old), nearly 60% of people in the oldest group (18–25) showed motor function stabilization, which is the main goal for older patients.

JEWELFISH is assessing Evrysdi’s safety, pharmacokinetics (the movement into, through, and out of the body), and pharmacodynamics (its effects on the body) in 174 people, ages 1 to 60 years, with all SMA types previously treated with other SMA therapies.

A total of 83 participants were treated previously with Genentech’s investigational compounds (including olesoxime), 76 with Spinraza (by Biogen), and 14 with Zolgensma (a gene therapy by Novartis and its subsidiary AveXis).

Preliminary one-year data showed that Evrysdi effectively raised SMN levels in these patients, and that its safety profile was consistent with that reported in other Evrysdi trials of patients not treated previously with an SMA-targeting therapy.

An open-label, Phase 2 trial, called RAINBOWFISH (NCT03779334), is still enrolling newborns up to 6 weeks old with a genetic diagnosis of SMA, but who have no evidence of symptoms (presymptomatic), at a dozen sites across eight countries, including the U.S. More information is available here.