Evrysdi Approved in Europe as First Oral, At-home Treatment

The European Commission has approved Evrysdi (risdiplam) as the first oral and at-home treatment for adults, children, and infants 2 months and older with nearly all types of spinal muscular atrophy (SMA).

Eligible patients include those with a clinical diagnosis of SMA type 1, 2, or 3 or carrying one to four copies of the SMN2 “backup” gene, whose copy numbers are associated with disease severity.

“Today’s approval of Evrysdi, the first and only SMA treatment with proven efficacy that can be taken at home, potentially transforms treatment options for a broad range of people with SMA living in the EU [European Union],”  Levi Garraway, MD, PhD, said in a press release. Garraway is chief medical officer and head of global product development at Roche, one of Evrysdi’s developers.

“By avoiding the need for in-hospital administration, Evrysdi can reduce the treatment burden on those living with SMA, their caregivers and healthcare systems,” Garraway said.

“We welcome today’s approval of Evrysdi for people with SMA in Europe, and are proud of the role we have played in its development and of our partnership with Roche,” said Nicole Gusset, PhD, the president of SMA Europe.

Gusset said that an organization’s recent survey showed that “a large proportion of people with SMA in the EU were not receiving an approved treatment which leaves them feeling helpless and frustrated.”

“It is vital that we work together with health authorities, regulators and industry to ensure we can get this medicine to the patients who need it as soon as possible,” she added.

Roche is working closely with all European stakeholders to accelerate patient access to the therapy and already had submitted reimbursement dossiers to health authorities in many countries to minimize access delay.

Health authorities in each European Union member state — as well as in Iceland, Norway, and Liechtenstein — now will decide separately whether to add Evrysdi to their respective public health programs, which allow patients to access treatments at low or no cost.

According to Roche, Evrysdi will be available to eligible patients in Germany in the coming days, and in France from early April through the Temporary Authorization for Use program, which allows access to treatments before completion of pricing and reimbursement negotiations.

The European Commission’s decision comes about one month after the Committee for Medicinal Products for Human Use, an arm of the European Medicines Agency, recommended Evrysdi’s approval under its accelerated assessment. That eligibility is offered to medicines considered to be of major interest for public health and therapeutic innovation.

It also follows similar decisions in the U.S., Brazil, Chile, Ukraine, South Korea, Georgia, and Russia. Identical approval requests are currently being reviewed by health authorities in 33 other countries, including Japan and China.

Evrysdi is a small molecule that works by increasing the levels of SMN, a protein essential for motor neuron and muscle health and whose production is impaired in people with SMA. 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.

The approval was based on top-line data from two ongoing Phase 2/3 clinical trials — FIREFISH (NCT02913482) and SUNFISH (NCT02908685) — that are investigating Evrysdi’s safety and effectiveness in nearly 300 patients, 2 months to 25 years old, with SMA types 1, 2, and 3.

FIREFISH’s top-line findings included 41 type 1 infants, ages 2 to 7 months (median of 5.3 months), while SUNFISH’s included 180 type 2 and 3 patients, aged 2 to 25 (median age of 9) and reliant on a wheelchair.

Notably, SUNFISH was the first placebo-controlled trial to enroll such a diverse — by age and disability level — SMA patient group.

Data showed that both trials met their main and most secondary goals, with Evrysdi treatment resulting in 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 therapy also was well-tolerated in both studies, with no Evrysdi-related adverse side effects leading to withdrawal or treatment discontinuation.

“We’re thrilled that Evrysdi, with proven efficacy and safety, has been rapidly approved in Europe so that the SMA community will now have access to a much needed convenient at-home treatment,” Stuart W. Peltz, PhD, co-founder and CEO of PTC Therapeutics, said in a separate press release.

“We thank the SMA community for their partnership, the trust they have placed in us and their unyielding commitment to achieve this significant milestone,” Garraway said.

The therapy’s clinical program also includes the global, Phase 2 JEWELFISH (NCT03032172) and RAINBOWFISH (NCT03779334) trials. The fully enrolled JEWELFISH study involves patients ages 6 months to 60 years, 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 is available here.

According to Roche, more than 3,000 people have been treated with Evrysdi in clinical trials, compassionate use programs, and real-world settings, with ages ranging from birth to more than 70 years.