How pamrevlumab works
Muscular dystrophy is characterized by progressive muscle fibrosis and weakening. Muscle fibrosis is the formation of excess connective tissue. Connective tissue normally surrounds muscle fibers and is essential for muscle function, but an excess can impair muscle function. Fibrosis is a hallmark of muscular dystrophies, contributing to muscle weakness.
Connective tissue growth factor (CTGF) is a pro-inflammatory protein — it promotes inflammation, which plays an essential role in wound healing but can also lead to muscle fibrosis. The inhibition of CTGF can improve muscle function irrespective of the cause of fibrosis. Pamrevlumab is a human antibody that recognizes and binds to CTGF, rendering it inactive.
Pamrevlumab in clinical trials
An open-label Phase 2 clinical trial (NCT02606136) is assessing the safety and efficacy of pamrevlumab in DMD patients who have lost the ability to walk. Every participant receives 35 mg per kg body weight of pamrevlumab every two weeks by infusion into the bloodstream for up to 156 weeks (three years). All participants were taking corticosteroids (deflazacort or prednisone) before enrollment.
Interim trial findings were analyzed after one year of treatment and showed that lung function was better preserved than expected, according to documented normal progression data of DMD. Spirometry results showed that the decline in lung function measured by percent predicted forced vital capacity (ppFVC) was 5.47 percent less than expected. The decline in percent predicted forced expiratory volume at one second (ppFEV1) was reduced 8.7 percent.
Heart muscle function progressively decreases in DMD patients. Magnetic resonance imaging (MRI) showed that the left ventricular ejection fraction (LVEF) increased by 0.29 percent after one year of pamrevlumab treatment. LVEF indicates how well the left ventricle of the heart pumps blood through the body.
Upper arm function and grip strength were measured by handheld myometry. Performance of the upper limb (PUL) scores decreased by only 1.53 points in patients treated with pamrevlumab compared to a decrease of 4.13 points in published results.
Pamrevlumab was well-tolerated, and most treatment-emergent adverse events were mild to moderate in severity.
The trial is expected to be completed by April 2021.
The U.S. Food and Drug Administration (FDA) designated pamrevlumab an orphan drug for the treatment of DMD in April 2019.
Last updated: 07/14/2019
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