Duchenne muscular dystrophy (DMD) is one of the most common childhood neuromuscular diseases, resulting from mutations in the dystrophin gene. These mutations lead to an absence of dystrophin protein, resulting in progressive muscle damage and replacement with fibrotic and fatty tissue. Although the clinical course of the disease is variable, death usually occurs due to cardiac and respiratory failure. Pamrevlumab is a human monoclonal antibody against connective tissue growth factor, currently under development in non-ambulatory DMD patients.
The preliminary analysis was conducted of 21-subjects who completed 52-weeks of treatment in the ongoing Phase-2 Study-079, assessing safety and efficacy of pamrevlumab in non-ambulatory DMD subjects. All 21 male subjects, age ≥12 years, on corticosteroids, received 35 mg/kg IV-infusions of pamrevlumab q2weeks. Safety was assessed regularly by laboratory results and physical examination, and efficacy was evaluated by pulmonary function tests, cardiac and muscle MRI.
Demographic: Median age at baseline was 15.8-years; median duration of being non-ambulatory, prior to enrollment was 3.4-years. DMD diagnosis was confirmed genetically.
Efficacy: All comparisons are with historical published data and no statistical analysis was performed. . Muscle function: the one-year change from baseline in the performance of upper limb (total score) showed less decline compared to (Ricotti, et al 2019). The Grip-strength score (newton) of the dominant and non-dominant hands, showed improvement compared to (Seferian et al 2015). Muscle fibrosis: assessed by MRI, showed strong correlation between changes from baseline to Week 52 in biceps brachii T2-mapping and change in PUL score. Pulmonary function: assessed by change from baseline at one-year in FVC%-predicted, FEV1%-predicted, and PEF%-predicted, showed less disease progression compared to data published by (Ricotti, et al 2019 and Meier, et al 2016). Cardiac function: was evaluated using left ventricular ejection fraction% assessed by cardiac MRI; the one-year change in LVEF% showed an improvement from baseline, compared to a reduction reported by (McDonald, et al 2018). Cardiac fibrosis: assessed by mass of late gadolinium enhancement showed a correlation between improvement in LVEF% and reduction in cardiac fibrosis, as mentioned in (Tandon, et al 2015).
Safety: Most TEAEs were mild-moderate in severity (CTCAE Grade 1-3). Most common TEAEs were headache, nasopharyngitis, back pain, vomiting and cough.
Conclusion: There is a high-unmet need for treatment in DMD. Pamrevlumab was well tolerated and demonstrated encouraging results in slowing disease progression of non-ambulatory DMD patients.