Scholar Rock eyes phase 3 after confirming effects of SMA drug

Gregory Carven, Ph.D., chief scientific officer at Scholar Rock (Business Wire)

Scholar Rock has reported 12-month data on spinal muscular atrophy (SMA) candidate apitegromab. The readout is in line with the six-month data drop that sent Scholar Rock’s stock price soaring in October, teeing the biotech up to move into a pivotal study by the end of the year. 

SMA has rapidly gone from a completely unmet need to a disease served by several products. Yet, there are still opportunities for treatments that can improve on existing products, either as single agents or as part combination therapies. Scholar Rock showed its selective inhibitor of the activation of latent myostatin—a mechanism of action distinct from current treatments—could be such an improvement on existing options last year.

The 12-month update broadly confirms the encouraging earlier findings. Interpretation of the results is again complicated by the design of the open-label study, but most effects seen at six months have proven to be durable.

In some cases, the efficacy results improved between the six and 12-month readouts. A cohort of kids with type 2 SMA aged two years and older who began treatment with Biogen and Ionis’ Spinraza  before turning five years old experienced a mean improvement of 5.6 points on a motor scale after receiving 20-mg/kg infusions of apitegromab on top of their existing therapy for six months. At 12 months, the improvement was 7.1 points. Scholar Rock saw a similar trend in the lower dose arm.

Around one-third of participants in both the low and high-dose arm experienced at least a 10-point improvement on the motor function scale at 12 months. Roughly 60% of patients had a five-point increase.

The two other cohorts lack such evidence of deepening responses. In patients with type 2 or non-ambulatory type 3 SMA who began treatment with Spinraza aged five years or older, the mean increase on the motor scale at 12 months was 1.2 points. That result comes from a per-protocol analysis that excludes a patient who missed three apitegromab doses due to COVID-19 restrictions. At six months, the mean increase across the full cohort was 1.4 points.

A third cohort saw a worsening of the scores from six to 12 months. On another disease scale, the ambulatory type 3 SMA patients improved by 0.5 points after six months. By 12 months, the group had experienced a mean decline of 0.3 points. Scholar Rock also tracked numerical declines in the proportion of patients with three- and five-point improvements, although the size of the 23-subject cohorts makes it hard to draw firm conclusions from the trend.

Scholar Rock is now gearing up to put apitegromab through a phase 3 study designed to confirm the signs of efficacy seen in phase 2. The trial is set to start by the end of the year. Scholar Rock is also working to expand use of apitegromab. A proof-of-concept study in Becker muscular dystrophy is planned for next year.