A phase 2 trial found evidence to support the cell therapy CAP-1002 for the treatment of late-stage Duchenne muscular dystrophy (DMD). These findings were published in The Lancet.

DMD is an X-linked disease affecting skeletal and cardiac muscle. The condition is progressive and severely reduces life expectancy. CAP-1002 is a cell therapy which was shown to have an acceptable safety profile and appeared to preserve upper limb and cardiac function during the phase 1 trial.

The Halt cardiomyopathy progression in Duchenne (HOPE-2) trial (ClinicalTrials.gov, Identifier: NCT03406780) was a phase 2, randomized, multicenter, double-blind, placebo-controlled trial conducted between 2018 and 2020 at 7 centers in the US. Boys (N=20) with late ambulatory and non-ambulatory DMD were randomized in a 1:1 ratio to receive placebo (n=12) or CAP-1002 (n=8). Upper limb function was evaluated using the Performance of Upper Limb (PUL) 1.2 and 2.0 instruments and cardiac function was evaluated using magnetic resonance imaging through 12 months.


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The individuals in the intervention and control cohorts were aged mean 14 (SD, 3.2) and 14 (SD, 2.9) years, body mass index was 23 (SD, 5) and 22 (SD, 5) kg/m2, 88% and 67% were White, 88% and 92% were non-ambulatory, and PUL score was 2-3 among 75% and 50%, respectively.

By month 12, the CAP-1002 recipients exhibited at 71% slowing of upper limb disease progression and a 10% slowing of cardiac disease progression.

For upper limb outcomes, CAP-1002 was favored for combined mid-level and distal-level PUL 1.2 (least squares mean difference [LSMD], 38.1; 95% CI, 11.1-65.1; P =.0076), global statistical test of PUL (LSMD, 24.4; 95% CI, 6.8-42.1; P =.0087), mid-level PUL 1.2 (LSMD, 36.2; 95% CI, 7.9-64.5; P =.014), total PUL 1.2 (LSMD, 29.7; 95% CI, 5.7-53.7; P =.017), and total PUL 2.0 (LSMD, 28.8; 95% CI, 1.5-56.1; P =.040) measures.

For cardiac outcomes, CAP-1002 was favored for left ventricular (LV) ejection fraction (LSMD, 45.7; 95% CI, 19.1-72.2; P =.002), global statistical test of cardiac measures (LSMD, 24.5; 95% CI, 9.0-40.0; P =.0066), LV end systolic volume (LSMD, 45.9; 95% CI, 11.8-79.9; P =.012), LV end systolic volume indexed (LSMD, 53.1; 95% CI, 13.6-92.6; P =.013), LV end diastolic volume indexed (LSMD, 47.8; 95% CI, 5.4-90.1; P =.031), and creatine kinase-MB over total creatine kinase (LSMD, 29.1; 95% CI, 4.0-54.2; P =.025) measures.

After receiving CAP-1002, 38% of patients reported a hypersensitivity reaction and 38% a treatment-emergent adverse event of hypersensitivity (n=1), dizziness (n=1), dysgeusia (n=1), and oropharyngeal pain (n=1). Among the placebo recipients, 17% experienced an adverse event of dysgeusia (n=2) and flushing (n=1).

This study was limited by its small sample size and short follow-up duration.

“CAP-1002 cell therapy appears to be safe and effective in reducing deterioration of upper limb function in patients with late-stage Duchenne muscular dystrophy,” the researchers concluded. Further studies are warranted to “confirm the therapeutic durability and safety of CAP-1002 beyond 12 months for the treatment of skeletal myopathy and cardiomyopathy in Duchenne muscular dystrophy.”

Disclosure: Multiple authors declared affiliations with industry. Please refer to the original article for a full list of disclosures.

Reference

McDonald CM, Marbán E, Hendrix S, et al. Repeated intravenous cardiosphere-derived cell therapy in late-stage Duchenne muscular dystrophy (HOPE-2): a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial. Lancet. 2022;399(10329):1049-1058. doi:10.1016/S0140-6736(22)00012-5