A phase 3 trial of Scholar Rock’s spinal muscular atrophy (SMA) candidate has hit its primary endpoint, sparking a 200%-plus premarket surge in the biotech’s stock price. Investors went wild despite the higher dose falling short of the targeted efficacy and Scholar Rock making no mention of a key secondary goal.
The phase 3 study compared apitegromab to placebo in nonambulatory SMA patients. A flurry of activity has given SMA patients two correctors and one gene therapy to choose from. However, all the products focus on the neuro component of the neuromuscular disease. Scholar Rock’s apitegromab, an inhibitor of myostatin activation, is at the head of a wave of assets designed to address the muscular component.
Investigators randomized 156 SMA patients aged 2 to 12 years to receive placebo or one of two doses of apitegromab. In a pooled analysis of both doses, Scholar Rock saw a 1.8-point improvement in motor function over placebo after 52 weeks. The p-value was 0.0192. The result sent the biotech’s share price up 212% to above $23 in premarket trading. The swell continued after market open, rising 327% to $31.72 as of mid-day Monday.
Scholar Rock’s statistical analysis plan prespecified the comparison of the pooled data and the higher, 20-mg/kg dose alone to placebo. If only one analysis cleared the 0.05 threshold for clinical significance, the other p-value would need to be 0.025 or lower to qualify as a statistical success.
Scholar Rock’s 20-mg/kg dose failed, achieving a 1.4-point improvement in motor function that resulted in a p-value of 0.1149. But the pooled analysis met the 0.025 threshold for success because of data from the lower, 10-mg/kg cohort. The biotech reported a 2.2-point improvement in the 10-mg/kg arm. Scholar Rock said it saw similar levels of target engagement at both doses.
Talking at a Morgan Stanley event last month, Scholar Rock’s chief financial officer Edward Myles said the trial was designed to detect a two-point difference in motor function between the treatment and placebo groups. The pooled analysis fell just short of that threshold, but 30.4% of patients on the study drug had a three-point or greater improvement, compared to 12.5% of their peers on placebo.
Myles highlighted a measure of upper limb mobility as a key secondary endpoint. The targeted patients cannot walk and, as such, upper limbs “are really, really critical” to their lives, the CFO said. The release about the top-line data makes no mention of whether the study met the secondary upper limb goal.
The details could matter, because Scholar Rock will face the challenge of persuading payers to cover a drug used in addition to existing, expensive SMA drugs—and because the biotech could need to hold off competition from other muscle-directed therapies. Biohaven is aiming to publish top-line phase 3 data on its candidate this year. Roche is enrolling patients in a phase 2/3 trial of its prospect.
Scholar Rock has identified its targeting of the latent form of myostatin as a differentiator, but its rivals are claiming their candidates have differentiating features, too. Biohaven’s pitch centers on the fact its candidate targets both myostatin and activin A signaling, two key regulators of muscle mass and adipose tissue.
Apitegromab has a small lead in the race to market, with Scholar Rock now aiming to file for approval in the U.S. and EU in the first quarter of 2025. If the biotech brings apitegromab to market, the drug will be its first product launch.
Editor's note: This story was updated to include changes in stock price.