World Muscle Society Congress 2022: Genentech, Fulcrum and Sarepta Present Latest Findings

2022-10-12

基因疗法

Courtesy gilaxia/Getty Images The World Muscle Society 2022 Congress is ongoing in Halifax, Canada, with numerous companies presenting cutting-edge research in neuromuscular diseases. Here’s a look at presentations from Genentech, Fulcrum Therapeutics and Sarepta Therapeutics. Genentech’s Evrysdi 2-Year Trial for SMA Genentech, a Roche company, presented new two-year data from the JEWELFISH trial of Evrysdi (risdiplam) in patients with Type 1, 2 or 3 spinal muscular atrophy (SMA). The results demonstrated the drug improved or maintained motor function while leading to rapid increases in SMN protein levels that were sustained after two years of receiving Evrysdi. The trial enrolled 174 patients six months to 60 years of age. All had been previously treated with other approved or experimental SMA therapies, including Biogen’s Spinraza (nusinersen). SMA is a genetic disorder beginning in the central nervous system that affects all the muscle in the body. It is the result of a lack of survival motor neuron (SMN) protein, which is essential for muscle development and movement. The company notes that JEWELFISH enrolled “the broadest and most diverse patient population ever studied in an SMA trial.” In addition to the range of ages, two-thirds, or 63%, of the participants were diagnosed as having very severe disease, and 83% had scoliosis. About 44% had previously received Spinraza with olesoxime, and 8% received Novartis’ Zolgensma (onasemnogene abeparvovec) with RG7800. Claudia Chiriboga, M.D., professor of neurology and pediatrics, department of neurology at Columbia University Medical Center, New York, stated the data “reinforces Evrysdi as a meaningful treatment option across SMA populations. The findings add to our confidence when making treatment decisions for previously treated patients in need.” Fulcrum’s FSHD Study of Losmapimod Fulcrum Therapeutics announced new data from the open-label extension (OLE) part of its Phase II ReDUX4 trial of losmapimod for treating FSHD, and it will also host a symposium entitled “Measuring Progression in FSHD: Implications for Clinical Trials.” The data from the OLE support previous results showing the drug modifies FSHD disease progress, preserving or improving muscle function. The ReDUX4 study enrolled 80 patients ages 18 to 65 with genetically confirmed FSHD1. They were randomized 1:1 to receive 15 mg losmapimod twice a day or placebo. After the initial 48-week period, all patients had the choice to enroll in the OLE segment, where all received losmapimod. Of the 77 patients who completed the 48-week segment, 99% enrolled in the OLE. The patients who were originally in the placebo arm who crossed over to losmapimod for the OLE and stayed on the drug through 95 weeks demonstrated trends that the disease was slowing or halting progression as measured by reachable workspace (RWS). The patients who were in the drug cohort initially and stayed for the OLE continued to demonstrate slowing or stopping of disease progression and improvement in muscle function, as measured by RWS. Bryan Stuart, CEO of Fulcrum, emphasized the importance of the data, stating, “The sustained ability to slow or halt the progression of FSHD over two years underscores the significance of our Phase III REACH trial and the potential of losmapimod to be the first approved treatment for FSHD.” Sarepta Presents Range of Programs Across Portfolio Sarepta Therapeutics presented new data from across its genetic medicine portfolio, including real-world evidence on eteplirsen in treated patients with Duchenne muscular dystrophy (DMD) amenable to exon 51 skipping. Sarepta also presented preclinical data from its gene therapy platform in support of the SRP-9001 (delandistrogene moxeparvovec) for treatment of DMD. From its RNA platform, the company presented interim Phase III ESSENCE data on casimersen in DMD patients amenable to Exon 45 skipping and interim analysis of the long-term observational EVOLVE study of eteplirsen, golodirsen or casimersen in routine clinical practice. From the company’s gene therapy programs, Sarepta presented analysis of adeno-associated virus (AAV) vector shedding after treating patients with SRP-9001. The company also presented pharmacokinetic/pharmacodynamic modeling data around AAV gene transfer therapy for DMD, as well as the pharmacology and efficacy of SRP-9001 in rat models of DMD. Sarepta also presented Health Economic Outcomes Research (HEOR) related to DMD treatments.