Roche to Start MANATEE, a Drug Combination Study, in Early 2022

22 October 2021

Roche will initiate 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?

Available SMA therapies aim to increase the amount of survival motor neuron (SMN) protein in the body (referred to as “SMN-targeted therapies”). The combination of an SMN-targeted therapy with a second approach targeting muscles may result in a complementary or added benefit. The idea is that this combinatorial strategy will simultaneously treat the underlying cause of SMA, as well as the symptoms of the condition [i].

About the molecule

GYM329 is an investigational anti-myostatin antibody that is designed to target skeletal muscles (i.e., those used for voluntary movement), 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 SMA Type 2.

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. People previously treated with either risdiplam (Evrysdi), nusinersen (Spinraza) or onasemnogene abeparvovec (Zolgensma) 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 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, the main part of the study, 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 in Part 1 is complete.

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. People who have 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.

[i] Cure SMA. Scientific Considerations For Drug Combinations.

[ii] Muramatsu, H et al 2021. Scientific Reports, 11(1).