We are developing apitegromab, a selective inhibitor of the activation of latent myostatin, with the aim of improving patients’ motor function. Rather than the traditional approach of blocking already activated, mature myostatin or the receptor, apitegromab selectively targets the precursor, or inactive, form of myostatin to block its activation in the muscle. By targeting the precursor form, apitegromab has demonstrated in in vitro studies that it offers potent and highly selective inhibition of myostatin while avoiding blocking the activity of other closely-related members of the TGFβ superfamily that may lead to undesirable side effects.
The TOPAZ Phase 2 proof-of-concept trial investigated apitegromab in patients with Type 2 and Type 3 SMA over a 12-month treatment period. A pre-planned interim analysis was conducted following a six-month treatment period and positive interim proof-of-concept data was announced in October 2020. Positive 12-month top-line results were announced in April 2021 and support further development of apitegromab as a potential muscle-directed therapy intended to be used in conjunction with available SMN upregulator therapies to help improve motor function for individuals with SMA.
The findings from TOPAZ informed the design of SAPPHIRE, a randomized, double-blind, placebo-controlled, phase 3 clinical trial to further investigate apitegromab in non-ambulatory people with Type 2 and Type 3 SMA. Start-up activities for SAPPHIRE commenced in November 2021.
“Our hope is to help individuals with SMA and improve their motor function.”
Ryan Iarrobino
Senior Vice President,
Clinical Development & Operations
Myostatin: A Closer Look
Myostatin is a member of the TGFβ superfamily of growth factors. It is expressed primarily in skeletal muscle cells to inhibit muscle growth, and works in concert with other growth factors and hormones to maintain appropriate muscle mass. Vertebrates that lack the myostatin gene display increased muscle mass and strength but are otherwise healthy.
Clinical Trials
SAPPHIRE is a randomized, double-blind, placebo-controlled, phase 3 clinical trial designed to further investigate apitegromab in non-ambulatory people with Type 2 and Type 3 SMA
TOPAZ Phase 2 proof-of-concept trial assessed the safety and efficacy of apitegromab in later-onset Spinal Muscular Atrophy (SMA Type 2 and Type 3). Topline 12-month results were shared in April 2021.
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