In response to our request, Roche is pleased to inform us about the initiation of MANATEE, a new global Phase 2/3 clinical study to evaluate the safety and efficacy of GYM329 (RO7204239), an investigational anti-myostatin antibody targeting muscle growth in combination with risdiplam in SMA.
Why a combination study?
This study draws on ten years of listening to and working with the global SMA community, who for a number of years now have shown a strong interest in the potential of combination treatments, the next generation in SMA research and development. By evolving existing partnerships with the community, exploring a combination of therapies with different mechanisms of action, Roche strives to transform the lives of people living with SMA and their families.
Current available SMA therapies aim to increase the amount of survival motor neuron (SMN) protein in the body (referred to as “SMN-targeted therapies”). Low levels of SMN protein is the underlying driver of SMA. The combination of an SMN-targeted approach and a second targeting skeletal muscle (the muscle used for movement under voluntary control) may result in a complementary or added benefit by addressing the underlying cause and the symptoms of the disease concurrently[i].
About the molecule
GYM329 is an investigational anti-myostatin antibody that is designed to target skeletal muscles, potentially increasing their size and growth[ii]. Myostatin plays an important role in the regulation of skeletal muscle size by controlling growth. Inhibiting myostatin may help muscles grow in size and strength. GYM329 in combination with risdiplam, which is designed to increase the amount of SMN protein throughout the body, has the potential to further improve motor function and outcomes for people living with SMA2.
MANATEE study overview
MANATEE is a global, Phase 2/3 study that will assess GYM329 in combination with risdiplam in ambulant (able to walk independently) children with SMA aged 2-10 years. Patients who have been previously treated with either risdiplam, nusinersen or onasemnogene abeparvovec are eligible, as well as those who have not received treatment before. Other eligibility criteria exist. Roche is exploring the combination in other patient populations in the future, including non-ambulant patients and in a broader age range. The MANATEE study consists of two parts:
- Part 1 will begin first and will assess the safety of two doses of GYM329 in combination with risdiplam, with the aim of selecting the optimal dose of GYM329 for Part 2 of the study. It is expected to enrol approximately 36 participants
- Part 2 is the main part of the study and will assess the efficacy and safety of the GYM329 dose selected in Part 1 when combined with risdiplam. It is expected to enrol approximately 144 participants. Part 2 will commence once the dose selection is complete in Part 1.
Participants will be randomly assigned to either a treatment group that receives risdiplam and GYM329, or a treatment group that receives risdiplam and a placebo. All participants in the study will receive a daily dose of risdiplam at the approved dose throughout the study, including those in the placebo group.
Approximately 15 sites have been selected to participate in Part 1 of the study in countries including Belgium, Germany, Italy, Poland, the Netherlands, the UK and the USA. Enrolment for Part 1 is anticipated to start in early 2022 and Part 2 at the end of 2023. Any patient family who has an interest in joining the study should discuss treatment decisions with their physician. Further information on the MANATEE study and the complete list of eligibility criteria will be accessible on ClinicalTrials.gov and ForPatients.Roche.com in the coming weeks.
As Roche prepares for this next phase of the overall Roche SMA clinical development programme, they would like to take the opportunity to thank SMA Europe, their investigators and study site staff who have helped contribute to the design and preparations for the trial. Roche will provide us with updates in the near future.
[i] Cure SMA. Scientific Considerations For Drug Combinations.
[ii] Muramatsu, H et al 2021. Scientific Reports, 11(1).