CHMP Favors EU Approval of Evrysdi as 1st Oral, At-home SMA Treatment

Evrysdi (risdiplam) has been recommended for approval in the European Union (EU) to treat spinal muscular atrophy (SMA) patients, ages 2 months and older, with a clinical diagnosis of type 1, 2, or 3, or with one to four copies of the SMN2 “backup” gene.

“Our close partnership with the SMA community has enabled the development of the first ‘at-home’ treatment for SMA in infants, children and adults with varying levels of disease severity, the majority of whom remain untreated,” Levi Garraway, MD, PhD, the chief medical officer and head of global product development at Roche, one of Evrysdi’s developers, said in a press release.

“Given its proven efficacy and strong safety profile, coupled with the convenience of an at-home administration, we expect Evrysdi to become the treatment of choice for SMA patients and their families,” Stuart W. Peltz, PhD, co-founder and CEO of PTC Therapeutics — also instrumental in developing Evrysdi — said in a separate press release.

The recommendation was made by the Committee for Medicinal Products for Human Use (CHMP), an arm of the European Medicines Agency. CHMP opinions are generally accepted by the European Commission (EC), which makes final decisions on therapy approval for the 27-state union. A decision is expected by the close of April.

Should it be approved, Evrysdi would become the first oral and at-home therapy for this patient population across Europe. Health authorities in each EU member state — as well as in Iceland, Norway, and Liechtenstein — will then decide separately on whether to add Evrysdi to their respective public health programs, where patients can access the treatment at low or no cost.

Roche is actively working with reimbursement and assessment bodies in these countries to enable broad and fast access to patients in anticipation of the EC decision.

CHMP’s opinion “marks another important advancement in ensuring Evrysdi is available to SMA patients around the globe,” Peltz said.

Evrysdi was approved in the U.S. in August to treat adults and children, 2 months and older, with all types of SMA; similar decisions soon followed in Brazil, Chile, Ukraine, South Korea, Georgia, and Russia. Health authorities in 30 other countries, including Japan and China, are currently reviewing the therapy for possible approval, Roche reported.

SMA is caused by low to no production of SMN, a protein essential for motor neuron and muscle health, due to mutations in the SMN1 gene. A nearly identical “backup gene,” called SMN2, has the ability to produce the SMN protein, but at much lower levels.

For this reason, the disease is less severe in people with more SMN2 copies. Typically, SMA patients have one to two copies of this gene, but some can have up to eight copies.

Evrysdi is a small molecule that works by boosting SMN2’s ability to produce functional SMN. A flavored liquid, it is administered daily at home by mouth or feeding tube. Its development was the result of a long-lasting collaboration between Roche, its subsidiary Genentech, PTC Therapeutics, and the SMA Foundation.

CHMP’s positive opinion was based on top-line data from the ongoing Phase 2/3 FIREFISH (NCT02913482) and SUNFISH (NCT02908685) trials, which are evaluating Evrysdi’s safety and effectiveness in a total of 221 patients, 1 month to 25 years old, with SMA types 1, 2, and 3.

The type 2 and 3 patients in SUNFISH range in ages from 2 to 25, making it the first placebo-controlled trial to include such a broad SMA patient group by age and disability level.

Results showed that both trials met their main and most secondary goals, with one year of Evrysdi’s use leading to significant improvements in survival, swallowing, breathing, and motor milestones in type 1 infants, and in motor function in children and young adults with types 2 and 3 disease.

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

Evrysdi was generally safe and well-tolerated, with the most common adverse events including upper respiratory tract infection, pneumonia, common cold, fever, constipation, rhinitis, diarrhea, headache, cough, and vomiting. No treatment-related safety findings led to study withdrawal.

The therapy’s clinical program also includes two global Phase 2 trials — JEWELFISH (NCT03032172) and RAINBOWFISH (NCT03779334). The fully enrolled JEWELFISH study is investigating Evrysdi in patients ages 6 months to 60 years old, including those previously treated with other SMA-targeting therapies.

RAINBOWFISH is still recruiting newborns up to 6 weeks old with a genetic diagnosis of SMA but no evidence of symptoms; more information can be found here.

According to Roche, more than 2,500 people have now been treated with Evrysdi in clinical trials, compassionate use programs, and real-world settings, with ages ranging from newborn infants to adults over 70 years old.