Scholar Rock Continues to Build Case for SMA Drug with New Data (Updated)

New data from Scholar Rock’s Phase II TOPAZ trial showed its investigational antibody, apitegromab, improves quality of life in type 2 and 3 spinal muscular atrophy (SMA) patients, the company announced Saturday.

In non-ambulatory type 2 SMA patients, 24 months of apitegromab treatment stabilized or induced continuous improvements in activities of daily living (ADL) and fatigue, as measured by the Pediatric Evaluation of Disability Inventory-Computer Adaptive Test (PEDI-CAT) and Patient Reported Outcome Measurement Information System (PROMIS) inventories, respectively.

PEDI-CAT improved by up to an average of three points and PROMIS by up to an average of five points after apitegromab treatment. These patients had been on maintenance nusinersen therapy before five years of age.

In a separate group of patients with types 2 and 3 SMA, PEDI-CAT improved by a mean of up to 0.7 points from baseline, indicating better or at least stabilized ADLs. PROMIS was also better by an average of 3.5 points relative to baseline. These patients were also treated with apitegromab for 24 months but had initiated nusinersen at five years or older.

Moreover, this second group of patients also saw a trend toward improvement in fatigability and endurance measures.

Saturday’s readout includes tertiary quality of life endpoint results from TOPAZ, drawn from one of its extension phases. In a statement, Jay Backstrom, M.D., M.P.H., chief executive of Scholar Rock, said these latest data complement apitegromab’s prior efficacy data well and further point to the potential of apitegromab as a treatment option for SMA patients.

"The initial findings demonstrate that the tertiary endpoint data from these measures show trends of continuous improvement with ADL, fatigue and muscle endurance over 24 months, which is promising and warrant further exploration," Backstrom told BioSpace. "

Fifty-four of the 55 patients in TOPAZ’s extension period have agreed to continue into the 36-month extension phase.

TOPAZ is an ongoing and proof-of-concept open-label study testing intravenous apitegromab in 58 patients with type 2 or 3 SMA. The study consists of a main treatment period. During this period, apitegromab was given every four weeks either as a monotherapy or in combination with nusinersen. The study also includes several 12-month extension periods to assess longer-term outcomes.

The primary outcome of TOPAZ is motor function, as measured by the Revised Hammersmith Scale (RHS) in ambulatory patients and by the Hammersmith Functional Motor Scale Expanded (HFMSE) in the non-ambulatory group. In June, the Cambridge, MA-based biotech reported extension data from TOPAZ, touting motor function gains in non-ambulatory patients.

HFMSE scores increased from an average of 3.6 points at baseline to 4.0 points after 24 months of treatment, a statistically significant effect. Excluding patients who had scoliosis surgery from the analysis further improved the mean HFMSE to 4.4 points.

Meanwhile, in ambulatory patients, mean RHS scores dropped by 0.7 points from baseline in those treated with the apitegromab-nusinersen combo, and by 2.8 points in those receiving monotherapy. These were not statistically significant, indicating that while no improvements were observed, Scholar Rock’s candidate could at least stabilize motor function in these patients.

The company is preparing to launch a Phase III trial of apitegromab, dubbed SAPPHIRE. Enrollment is ongoing. Scholar Rock presented the study’s design at the 17th International Congress on Neuromuscular Diseases in July.

"Data from this Phase III placebo-controlled trial is expected to form the basis of our marketing authorization applications," Backstrom said.