New Phase 2 TOPAZ Trial Data Indicate Positive Trends in Quality-of-Life Measures Over 24 Months with Apitegromab for Nonambulatory Patients with Types 2 and 3 SMA
Scholar Rock (NASDAQ: SRRK) has announced new quality-of-life data from its Phase 2 TOPAZ trial extension, indicating sustained improvements in daily activities, fatigue, and muscle endurance for non-ambulatory patients with spinal muscular atrophy (SMA) over 24 months. Data presented in Barcelona suggest apitegromab may offer significant benefits, particularly for patients receiving nusinersen. No safety concerns were reported, with the majority of patients opting to continue treatment into a 36-month extension.
- Sustained improvements in quality-of-life measures over 24 months for SMA patients.
- Positive trends in activities of daily living (ADL) and reduced fatigue reported.
- No safety risks identified; adverse events were consistent with the underlying patient population.
- Limited sample sizes in the trial may affect the generalizability of the data.
- Further exploration is warranted due to exploratory nature of the quality-of-life data.
- Tertiary endpoint data show trends of continuous improvement in activities of daily living, fatigue, and endurance over 24 months
- These data indicate the potential for sustained improvement in quality-of-life measures for patients with symptomatic SMA and offer further evidence of possible durable effects of apitegromab
“SMA can have a significant impact on the ability to perform daily activities but there is limited research on potential interventions to improve quality-of-life measures, such as increasing muscle endurance and reducing fatigue.1,2 These positive TOPAZ data indicate sustained improvements of quality-of-life measures over 24 months in the patient population studied,” said
The TOPAZ trial assessed activities of daily living (ADL), fatigue, and muscle endurance by three tertiary endpoint measures:
- The Pediatric Evaluation of Disability Inventory-Computer Adaptive Test (PEDI-CAT) measures pediatric abilities through three functional domains, daily activities, mobility, and social cognition;3
- Patient Reported Outcome Measurement Information System (PROMIS) measures mild subjective feelings of tiredness to debilitating and sustained feelings of exhaustion, with lower scores reflecting less fatigue;4,5 and
-
Endurance Shuttle Box and
Block Test (ESBBT), a muscle endurance measurement tool, evaluates how fast a patient fatigues with the added measure of endurance6 and may be complementary to outcome measures that focus on arm motor function, such as the Revised Upper Limb Module (RULM) assessment.
The tertiary endpoint data from these measures show trends of continuous improvement over 24 months. These data are relevant for informing the therapeutic hypotheses being evaluated in the Phase 3 SAPPHIRE trial. Limitations of these exploratory quality-of-life data analyses include small patient sample sizes in an open-label study, and further exploration is warranted. Specifically, the data found:
- Nonambulatory Type 2 patients (aged two or older who began receiving nusinersen maintenance therapy before age five) reported stabilization or continuous improvements in ADL up to a mean change from baseline of 3 points (n=14) in PEDI-CAT scores and fatigue up to a mean change from baseline of 5 points (n=10) in PROMIS scores over 24 months of apitegromab.
- Nonambulatory Types 2 and 3 patients (aged five to 21 who began receiving nusinersen maintenance therapy at or after age five) reported stabilization or increases in ADL up to a mean change from baseline of 0.7 points (n=8) in PEDI-CAT scores, and less fatigue up to a mean change from baseline of 3.5 points (n=2) in PROMIS scores over 24 months of apitegromab. Additionally, these patients also experienced trends in improvements in fatigability and endurance measures based on mean change in ESBBT activities. The trends of improvement with ESBBT are consistent with the previously reported increases in RULM scores observed in the TOPAZ trial at 24 months.
These findings complement previously reported data from the TOPAZ trial 24-month extension period that demonstrated sustained and durable improvements in motor function as measured by the Hammersmith Functional Motor Scale Expanded (HFMSE) and RULM in patients with nonambulatory Types 2 and 3 SMA.
No safety risks were identified over 24 months of treatment. The incidence and severity of adverse events were consistent with the underlying patient population and nusinersen 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.
Of the 55 patients who completed the 24-month TOPAZ extension period, 54 have opted to continue treatment in the 36-month extension period.
About the Phase 2 TOPAZ 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. The trial enrolled 58 patients in the
About Apitegromab
Apitegromab is a selective inhibitor of the activation of myostatin and is an investigational product candidate for the treatment of patients with spinal muscular atrophy (SMA). 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.
About SMA
Spinal muscular atrophy (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
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Forward-Looking Statements
This press release contains "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995, including, but not limited to, statements regarding Scholar Rock’s future expectations, plans and prospects, including without limitation, Scholar Rock’s expectations regarding its growth, strategy, progress and timing of its clinical trials for apitegromab, and other product candidates and indication selection and development timing, the ability of any product candidate to perform in humans in a manner consistent with earlier nonclinical, preclinical or clinical trial data, and the potential of its product candidates and proprietary platform. The use of words such as “may,” “might,” “could,” “will,” “should,” “expect,” “plan,” “anticipate,” “believe,” “estimate,” “intend,” “future,” “potential,” or “continue,” and other similar expressions are intended to identify such forward-looking statements. All such forward-looking statements are based on management's current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. These risks and uncertainties include, without limitation, that preclinical and clinical data, including the results from the Phase 2 clinical trial, including extension periods, of apitegromab are not predictive of, may be inconsistent with, or more favorable than, data generated from future clinical trials of the same product candidate, including, without limitation, the Phase 3 clinical trial of apitegromab in SMA, Scholar Rock’s ability to provide the financial support, resources and expertise necessary to identify and develop product candidates on the expected timeline, the data generated from Scholar Rock’s nonclinical and preclinical studies and clinical trials, information provided or decisions made by regulatory authorities, competition from third parties that are developing products for similar uses, Scholar Rock’s ability to obtain, maintain and protect its intellectual property, Scholar Rock’s dependence on third parties for development and manufacture of product candidates including, without limitation, to supply any clinical trials, Scholar Rock’s ability to manage expenses and to obtain additional funding when needed to support its business activities and establish and maintain strategic business alliances and new business initiatives, and the impacts of public health pandemics such as COVID-19 on business operations and expectations, as well as those risks more fully discussed in the section entitled "Risk Factors" in Scholar Rock’s Quarterly Report on Form 10-Q for the quarter ended
1 Wan HWY, Carey KA, D'Silva A, et al. Orphanet J Rare Dis. 2020;15:70.
2 Yang M. et al.
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5 Belter L, et al.
6 Cure SMA. Best Practices for Physical Therapists and Clinical Evaluators in Spinal Muscular Atrophy (SMA). 2021. Available at: https://www.curesma.org/wp-content/uploads/2021/09/Clinical-Evaluators-Best-Practices-13-August-2021.pdf.
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FAQ
What are the results of the Phase 2 TOPAZ trial for Scholar Rock's apitegromab?
What does the new quality-of-life data from Scholar Rock imply for SMA patients?
Are there any safety concerns with apitegromab from the TOPAZ trial?