Genentech, a member of the Roche Group, announces new two-year data from the JEWELFISH study evaluating Evrysdi (risdiplam) in people with Type 1, 2 or 3 spinal muscular atrophy (SMA) aged 6 months to 60 years at time of enrollment. Patients had been previously treated with other approved or investigational SMA-targeting therapies, including nusinersen (Spinraza) or onasemnogene abeparvovec (Zolgensma). Data showed Evrysdi improved or maintained motor function and led to rapid increases in SMN protein levels which were sustained after two years of treatment. These data will be presented at the 27th World Muscle Society (WMS) congress, October 11-15, 2022.

“The consistent safety profile and exploratory efficacy we have seen in the JEWELFISH study, the largest ever conducted in previously treated patients, reinforces Evrysdi as a meaningful treatment option across SMA populations,” said Dr. Claudia Chiriboga, Professor of Neurology and Pediatrics, Department of Neurology, Columbia University Medical Center, New York. “The findings add to our confidence when making treatment decisions for previously-treated patients in need.”

The JEWELFISH study enrolled the broadest and most diverse patient population ever studied in an SMA trial. Of the 174 people enrolled, 36% (n=63) were adults, 63% (n=105) had a Hammersmith Functional Motor Scale Expanded (HFMSE) score of less than 10 at baseline, meaning their disease was very severe, and 83% (n=139) had scoliosis. Forty-four percent (n=76) of those enrolled had previously been treated with nusinersen (Spinraza), 41% (n=71) with olesoxime*, 8% (n=14) with onasemnogene abeparvovec (Zolgensma) and 7% (n=13) with RG7800*.

People with SMA are unable to produce enough survival motor neuron (SMN) protein, leading to debilitating and potentially fatal muscle weakness. The study showed Evrysdi led to a two-fold increase in median SMN protein levels versus baseline after four weeks of treatment in all patient groups, irrespective of previous treatment. The SMN protein levels achieved after four weeks of treatment were maintained for over two years.

Observed through exploratory efficacy endpoints, the study also suggests maintenance of motor function was sustained at two years of treatment as measured by change from baseline in Motor Function Measure 32 (MFM-32), Revised Upper Limb Module (RULM) and HFMSE total scores compared to the natural history of SMA in untreated patients. A recent survey conducted by patient advocacy group SMA Europe showed that more than 96% of people with SMA viewed disease stabilization as progress in terms of their expectations of treatment.

“These important data demonstrate the safety and efficacy of Evrysdi in a broad, real-world population of people previously treated with an SMA-targeting therapy,” said Levi Garraway, M.D., Ph.D., Genentech’s chief medical officer and head of Global Product Development. “Those enrolled in JEWELFISH had very severe disease, with over 80% having scoliosis, so maintaining motor function–especially for a progressive disease–can be potentially life-changing.”

The overall adverse event (AE) and serious adverse event (SAE) profiles observed with Evrysdi treatment in JEWELFISH were reflective of underlying disease. The rate of AEs decreased by more than 50% between the first and second six-month period, and then remained stable thereafter. The rate of SAEs, including pneumonia, decreased throughout the 24-month period, with a total reduction of more than 50% by the second year. The most common AEs (reported in ≥12% of all patients; n=173) were pyrexia (24%), upper respiratory tract infection (21%), headache (18%), nasopharyngitis (16%), diarrhea (14%), nausea (13%) and cough (12%). The most common SAEs (reported in >2% of all patients) were pneumonia (3%), respiratory failure (2%), respiratory distress (2%), lower respiratory tract infection (2%) and upper respiratory tract infection (2%). The most common AEs/SAEs were consistent with those observed in treatment-naïve patients in our other three trials. Low rates of discontinuation from the study were observed, with a 5% rate per year over the 24-month period.

Genentech leads the clinical development of Evrysdi as part of a collaboration with the SMA Foundation and PTC Therapeutics.

*RG7800 and olesoxime are no longer in development as investigational treatments for patients with SMA.

[Source(s): Genentech, Business Wire]