Evrysdi Open to Eligible Patients in UK Through Early Access Program

Evrysdi (risdiplam), Roche’s oral therapy for spinal muscular atrophy (SMA), will be available to select patients in the U.K. before its potential regulatory approval through an Early Access to Medicines Scheme (EAMS).

Eligible patients include those with type 1 and 2 disease, ages 2 months and older, who are not suitable for other disease-modifying treatments — Biogen’s Spinraza (nusinersen) and Novartis’ gene therapy Zolgensma, according to an announcement on Spinal Muscular Atrophy UK’s website.

An EAMS gives people with life-threatening or seriously debilitating conditions and a clear unmet medical need access to therapies not yet approved for commercial use.

The decision to include Evrysdi in U.K.’s EAMS came eight months after Roche announced the launch of a worldwide Pre-Approval Access/Compassionate Use Program.

It was based on a positive scientific opinion granted by the country’s Medicines and Healthcare Products Regulatory Agency (MHRA), which controls the EMAS process.

The scientific opinion is designed to provide both physicians and patients with information on the therapy’s benefit/risk balance based on available data, supporting a decision as to whether they want to use an unapproved treatment. The opinion stands for one year and can be renewed.

Evrysdi works by raising the levels of SMN — a protein essential for motor neuron and muscle health, and lacking in people with SMA — throughout the body. Its development came out of a long-lasting collaboration between Roche, its subsidiary Genentech, PTC Therapeutics, and the SMA Foundation.

The therapy is currently under accelerated review for marketing authorization by the European Medicines Agency — with a decision expected around mid-2021 — following its approval in the U.S. as the first oral and at-home daily treatment for all SMA types, ages 2 months and older.

It is also being reviewed by regulatory agencies in Brazil, Chile, China, Indonesia, Russia, South Korea, and Taiwan.

Evrysdi’s applications were supported by positive results 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 the safety and effectiveness of Evrysdi in 221 people with SMA types 1, 2, and 3 from 1 month to 25 years old. Top-line data showed that both trials met their main and most secondary goals, with one year of Evrysdi treatment leading to significant improvements in swallowing, breathing, and motor milestones in type 1 infants, and in motor function in children and young adults with types 2 and 3 disease.

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, a main goal for older patients.

The most common Evrysdi-associated adverse events included upper respiratory tract infection, fever, pneumonia, constipation, and common cold and rhinitis in type 1 SMA patients; diarrhea, rash, and joint pain were common side effects in those with types 2 and 3 disease.

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 patients, ages 1 to 60 years old, previously given other SMA-targeting therapies.

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 trials of patients not on a previous therapy.

Under the EAMS, Evrysdi will be available to U.K. patients not eligible for the one-time gene therapy Zolgensma — available to people with almost all SMA types weighing up to 21 kilograms (about 46 pounds) — and for those whose severe scoliosis (or surgery to correct it) make Spinraza’s spinal injections challenging or unfeasible.

According to a previous press release from Britain’s Treat SMA, patients not responding to Spinraza as anticipated may also be eligible to switch to Evrysdi, which requires a three-month treatment-free period before its start. Patients, however, will not be allowed to move to Evrysdi based solely on its easier mode of administration or due to Spinraza’s long waiting list, the release noted.

RAINBOWFISH (NCT03779334), an open-label Phase 2 trial of Evrysdi, is still recruiting newborns up to 6 weeks old with a genetic diagnosis of SMA but no evidence of symptoms (presymptomatic) at sites across eight countries. More information is available here.