Scholar Rock Raises $205 Million on Positive Mid-Stage Extension Data in SMA

Scholar Rock raised $205 million in a registered direct offering as share rose on positive phase 2 TOPAZ trial extension data demonstrating sizeable and sustained motor function improvement at 24 months with its lead compound apitegromab for non-ambulatory patients with types 2 and 3 spinal muscular atrophy.

Photo: Nagesh Mahanthappa, founding CEO and president of Scholar Rock

The offering comes one month after the company said it was cutting 25 percent of its workforce and Shares rose 20 percent on the news and prioritizing its R&D activities to support two clinical programs, one of which is for apitegromab in spinal muscular atrophy (SMA). The size of the offering is more than Scholar Rock’s market cap ahead of reporting results of the apitegromab extension trial.

SMA is a rare, and often fatal, genetic disorder that typically manifests in young children. An estimated 30,000 to 35,000 patients are afflicted with SMA in the United States and Europe. It is characterized by the loss of motor neurons, atrophy of the voluntary muscles of the limbs and trunk and progressive muscle weakness. The underlying pathology of SMA is caused by insufficient production of the SMN (survival of motor neuron) protein, essential for the survival of motor neurons, and is encoded by two genes, SMN1 and SMN2. While there has been progress in the development of therapeutics that address the underlying SMA genetic defect, via SMN-dependent pathways, there continues to be a high unmet need for therapeutics that directly address muscle function.

Scholar Rock reported new data from the phase 2 TOPAZ trial extension period evaluating patient outcomes after 24-months of treatment, which support sustained and continued improvement with apitegromab for non-ambulatory patients with Types 2 and 3 SMA receiving an SMN therapy. Detailed results were presented at the Cure SMA Research & Clinical Care Meeting on June 17.

“The 24-month results provide long-term data and evidence, underscoring the findings of the 12-month primary treatment period of the TOPAZ trial in which patients receiving apitegromab experienced sizable motor function gains,” said George Nomikos, senior vice president of Clinical Sciences, head of Muscle Therapeutic Area of Scholar Rock. “This durability and continued increase in motor function support the transformative potential of apitegromab for patients suffering with SMA.”

Apitegromab is a selective inhibitor of the activation of myostatin, a member of the TGFβ superfamily of growth factors, is expressed primarily by skeletal muscle cells, and the absence of its gene is associated with an increase in muscle mass and strength in multiple animal species, including humans. Scholar Rock believes that inhibiting myostatin activation with apitegromab may promote a clinically meaningful improvement in motor function in patients with SMA.

“These data support apitegromab’s potential to meaningfully improve the lives of non-ambulatory patients with Types 2 and 3 SMA,” said Nagesh Mahanthappa, founding CEO and president of Scholar Rock. “As a company, we are dedicated to the SMA community and are urgently enrolling patients in our ongoing pivotal phase 3 SAPPHIRE trial.”

The TOPAZ trial is an ongoing proof-of-concept, open-label phase 2 trial evaluating the safety and efficacy of apitegromab in patients with Types 2 and 3 SMA. In the main treatment period, patients were dosed intravenously every four weeks as monotherapy or with nusinersen, an approved SMN therapy marketed by Biogen as Spinraza. The trial enrolled 58 patients in the United States and Europe. All 35 non-ambulatory patients (Cohorts 2 and 3) and 12 of 23 ambulatory patients (Cohort 1) were receiving nusinersen (Spinraza) maintenance therapy. The primary efficacy endpoints were mean change from baseline in Revised Hammersmith Scale (RHS) score at 12 months for the ambulatory population (Cohort 1), and mean change from baseline in HFMSE score at 12 months for non-ambulatory population (Cohorts 2 and 3). The trial also includes multiple 12-month extension periods designed to evaluate longer-term patient outcomes.

Additional endpoints included mean change from baseline in RULM, an assessment specifically designed for upper limb function in patients with SMA. The HFMSE is a validated measure for the assessment of gross motor function in SMA, while the RULM is validated to evaluate upper limb motor performance by evaluating tasks which correspond to the ability to perform various everyday activities with their hands and arms.

For this 24-month evaluation, an observed case analysis was conducted, which pooled all the non-ambulatory patients (Cohorts 2 and 3) and was based upon the available data for given timepoints. This analysis population included patients receiving either low dose (2 mg/kg) or high dose (20 mg/kg) apitegromab (inclusive of patients in Cohort 3 who switched from 2 mg/kg to 20 mg/kg in Year 2) and did not exclude any patients who had missed apitegromab doses due to study site access restrictions from COVID-19.

Non-ambulatory patients (age range of 2 to 21 years old) with valid HFMSE assessments had sizable, sustained gains in HFMSE scores at 24 months from baseline (prior to first dose of apitegromab), while RULM scores continued to increase at 24 months.

Dose response continued to be observed across the 24 months of apitegromab administration based upon HFMSE scores and pharmacodynamic data (target engagement as measured by serum latent myostatin concentrations), with signs that there may be further HFMSE increases as non-ambulatory patients originally receiving the low dose switched to the high dose treatment.

Data at 24-months for ambulatory patients with Type 3 SMA (Cohort 1) suggest stability of Revised Hammersmith Scale (RHS) scores in patients receiving 20 mg/kg of apitegromab and nusinersen. The mean RHS change from baseline at 24-months was ‑0.7 points for the apitegromab and nusinersen subgroup and ‑2.8 points for the apitegromab monotherapy subgroup. A subset of individuals in Cohort 1 had RHS improvements, as reflected by 42.9 percent (9/21) of patients having ≥1-point RHS increases from baseline at 24 months and 23.8 percent (5/21) ≥3-point RHS increases from baseline at 24 months.

Of the 55 patients who completed the 24-month TOPAZ extension period, 54 have opted to continue treatment in the 36-month extension period.

Consistent with the 12-month safety data, no serious safety risks were identified as part of the analysis of the cumulative 24-month data. The incidence and severity of adverse events were consistent with the underlying patient population and background therapy. The five most common treatment-emergent adverse events (TEAEs) were headache, pyrexia, upper respiratory tract infection, cough, and nasopharyngitis. No deaths or serious adverse reactions have been observed with apitegromab. A total of 14 serious TEAEs have been reported over the 24-month treatment period, all assessed by the respective trial investigator as unrelated to apitegromab.

Scholar Rock’s SAPPHIRE phase 3 clinical trial is evaluating the safety and efficacy of apitegromab in non-ambulatory patients with Types 2 and 3 SMA who are receiving SMN therapy (either nusinersen or risdiplam (Roche’s Evrysdi)). Approximately 156 patients aged 2-12 years old are anticipated to be enrolled in the main efficacy population. SAPPHIRE is expected to enroll 55 sites in the U.S. and Europe.

The U.S. Food and Drug Administration has granted Fast Track, Orphan Drug and Rare Pediatric Disease designations, and the European Medicines Agency (EMA) has granted Priority Medicines (PRIME) and Orphan Medicinal Product designations, to apitegromab for the treatment of SMA.

Author: Rare Daily Staff