Genentech stops emugrobart program for SMA after clinical trial results
Study found no consistent motor function benefit vs. Evrysdi alone
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- Genentech halted emugrobart development for SMA after early trial results showed no consistent motor function benefit.
- The MANATEE trial found emugrobart, combined with Evrysdi, did not consistently improve muscle growth or motor function.
- Despite being well tolerated, Genentech will not advance the drug but remains committed to advancing care for people with SMA.
Genentech will not advance emugrobart (GYM329) into Phase 3 development, after early results from a clinical trial testing it in combination with Evrysdi (risdiplam) in people with spinal muscular atrophy (SMA).
According to a letter to the SMA community, this “difficult decision” follows results from the first part of the MANATEE trial (NCT05115110), which showed that “emugrobart did not consistently deliver the improvements we hoped for in muscle growth and motor function compared to treatment with [Evrysdi] alone in people living with SMA,” wrote Gina Truslow, director of patient advocacy relations, on behalf of the Genentech SMA Team.
Trial tested emugrobart with Evrysdi
The letter was also shared by Cure SMA, which, together with Genentech, expressed “sincerest thanks to the individuals and families who took part in the phase 2 trial of emugrobart (MANATEE).”
SMA is chiefly caused by mutations in the SMN1 gene, which result in a deficiency of the SMN protein. Without this protein, motor neurons — the nerve cells that coordinate movement — become damaged and die, leading to SMA symptoms.
Another gene, SMN2, can also produce SMN, but a slight difference in its DNA sequence limits the amount of functional SMN it produces to 10%–15% of the protein produced by SMN1. Evrysdi, a currently approved therapy for SMA marketed by Genentech and Roche, works by increasing the production of functional SMN protein through the SMN2 gene.
Emugrobart is an antibody designed to block myostatin, a protein found in muscles. Myostatin prevents the overgrowth of skeletal muscles, those used for voluntary movement. Studies have shown that blocking myostatin increases muscle mass.
The MANATEE trial assessed the safety, efficacy, and pharmacological properties of emugrobart in combination with Evrysdi. Patients previously treated with approved SMA disease-modifying therapies — including Evrysdi, Spinraza (marketed by Biogen), or Zolgensma (marketed by Novartis) — could be eligible.
Part 1 (Phase 2) included children with SMA who were either able to walk (ages 2 to 10) or unable to walk (ages 5 to 10), and served as a dose-finding stage to inform a potential Phase 3 part of the study.
Program halted after trial did not meet expectations
Although emugrobart was well tolerated, with no serious adverse events that led to treatment discontinuation, the company decided not to advance to the second part of the trial, which was designed to follow a successful first part.
“We recognise this news will be disappointing to the SMA community. We are profoundly grateful to the study participants, their caregivers, and study sites for their contributions to this important research. We would also like to use this opportunity to express our sincere thanks to the US SMA community for your support and ongoing advice regarding the clinical development of emugrobart in SMA,” Truslow stated.
The company is working with study doctors to ensure safe discontinuation of emugrobart and follow-up assessments. For participants in countries where Evrysdi is not reimbursed, the company may support continued access to that treatment.
“Roche and Genentech remain committed to advancing quality care for people living with SMA and we plan to share the data from MANATEE Part 1 at an upcoming medical conference so that this research can also help to inform the development of future treatments,” Truslow added.
