Apitegromab linked to improved outcomes for those with spinal muscular atrophy

Key takeaways:

• The study included 58 individuals with SMA types 2 and 3 who were treated with IV apitegromab for 52 weeks.
• At 36 months, treatment resulted in statistically significant improvements in motor function and mobility.

Treatment with apitegromab was linked to improved muscle strength and range of motion, while being safe and well-tolerated in those with spinal muscular atrophy types 2 and 3, according to a poster presentation.

“Improving and sustaining muscle function amongst those with residual weakness following new [spinal muscular atrophy] treatments is the best, and maybe only, way to maximize motor function and help those living with SMA achieve greater independence,” Thomas O. Crawford, MD, professor of neurology and co-director of the Muscular Dystrophy Association Clinic at Johns Hopkins Medicine, told Healio in an email in response to a poster presented at the 2024 Muscular Dystrophy Association Clinical & Scientific Conference.

Crawford and colleagues aimed to evaluate safety and efficacy of apitegromab, an investigational, fully human monoclonal antibody in nonambulatory children, adolescents and adults with SMA types 2 or 3, over 36 months.

The TOPAZ clinical trial is a 52-week, multicenter, phase 2 study conducted across 16 location in the United States and Europe. A total of 58 participants were divided into two treatment groups: administered either 2 mg/kg or 20 mg/kg IV apitegromab, alone (n = 11) or in combination with nusinersen (n = 47). Those who completed the initial study could enroll in three sequential extension periods of 52 weeks each, where all participants received 20 mg/kg apitegromab per month.

Efficacy analysis included the nonambulatory population from the TOPAZ study (n = 35) over 36 months, while safety analysis included all 58 individuals enrolled. Muscle function was measured by the Hammersmith Functonal Motor Scale-Expanded (HFMSE), Revised Upper Limb Module (RULM) and WHO motor development milestones. Daily activities and mobility were evaluated by the Pediatric Evaluation of Disability Inventory Computer Adaptive Test (PEDI-CAT) and self-reported or caregiver proxy of perceived fatigue was assessed using the PROMIS Fatigue questionnaire.

According to results, mean change in both HFMSE and RULM demonstrated sustained improvements (2.8 to 4; 0.6 to 2.4, respectively) measured from month 6 to month 36, while similar improvements were also found in both PEDI-CAT domain (1.3 to 2.2 in daily activities; 1.4 to 1 in mobility domain) and PROMIS perceived fatigue (1.4 to -4.6).

Data further showed improvement in WHO motor milestones, while results on patient-caregiver-reported outcomes were consistent with motor function improvements assessed by HFSME and RULM. Apitegromab’s safety profile was also consistent with prior research.

“Over a 36-month period, we observed an improvement in [Hammersmith Functonal Motor Scale-Expanded] measurements of motor function,” Crawford told Healio. “Highlighting differences that demonstrate potential to meaningfully change the course of [spinal muscular atrophy] patients’ day-to-day activities.”