How pamrevlumab works
Pamrevlumab is a fully human antibody designed to bind to and block the activity of connective tissue growth factor (CTGF), a pro-inflammatory protein that promotes wound healing and fibrosis (scarring), and is found at abnormally high levels in the muscles of DMD patients. Progressive, abnormal muscle fibrosis is a hallmark of muscular dystrophies, contributing to muscle weakness and injury, including to cardiac muscle — a major complication of DMD.
By blocking CTGF, the therapy, administered directly into the bloodstream, is expected to suppress muscle fibrosis, thereby preventing the decline in patients’ motor, lung, and heart function, and possibly improving their status.
Pamrevlumab in clinical trials
An open-label Phase 2 clinical trial (NCT02606136) is assessing the safety and effectiveness of pamrevlumab in 21 boys and young men, ages 12 to 25, with DMD who have lost the ability to walk independently. Participants, recruited at 10 sites across the U.S., are receiving pamrevlumab (35 mg/kg of body weight) every two weeks for up to 156 weeks, or three years. All were taking corticosteroids, which include Emflaza (deflazacort) or prednisone, before enrollment.
Early, one-year data, presented at the 2019 Parent Project Muscular Dystrophy conference, highlighted that the therapy was generally well-tolerated and showed potential to improve patients’ heart function, and preserve lung function and upper limb strength.
Particularly, treated patients showed a 0.29% increase in left ventricular ejection fraction — which measures how well the left ventricle of the heart pumps blood through the body — and a 5–8.7% lesser-than-expected decline in two lung function tests, compared with that reported for untreated patients. Likewise, pamrevlumab also either improved upper limb performance and hand grip strength or lessened the decline. Notably, improvements were accompanied by a reduction in muscle scarring in the upper arm.
Most adverse events were mild to moderate in severity, with the most commonly reported including headache, vomiting, common cold, cough, and back pain.
The trial is expected to finish by January 2023.
LELANTOS, an international study, is expecting to recruit up to 90 boys and men with DMD, ages 12 and older, who are unable to walk alone, while the U.S.-based LELANTOS-2 trial aims to enroll about 70 DMD boys, ages 6–12, who are able to walk independently.
In both studies, participants will be randomly assigned to either pamrevlumab (35 mg/kg) or a placebo, given every two weeks for up to a year, in addition to oral corticosteroids.
LELANTOS’s main goal is to assess changes in the performance of upper limb 2.0 scale, which measures upper limb function specifically in DMD patients. Secondary goals include changes in patients’ lung health, grip strength, and heart function.
The primary goal of LELANTOS-2 is to evaluate changes in the scores of the North Star Ambulatory Assessment, a 17-item scale of motor function used to monitor disease progression and treatment effects. Secondary goals consist of changes in various muscle function tests measuring the time patients take to climb four stairs, run or walk 10 meters (about 11 yards), and stand from a lying position. Time to loss of walking ability will also be assessed.
Participants who complete the yearlong trials may be eligible to enter an open-label extension study, in which all will receive pamrevlumab and corticosteroids.
The U.S. Food and Drug Administration granted pamrevlumab orphan drug designation in April 2019 and fast track designation in April 2021 for the treatment of DMD. Such designations provide financial and regulatory incentives to speed a therapy’s development and review.
FibroGen is also developing pamrevlumab as a potential treatment of other diseases in which lesser scarring may be beneficial, including idiopathic pulmonary fibrosis and locally advanced pancreatic cancer.
Last updated: May 5, 2021
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