Despite pamrevlumab being generally safe and well tolerated, the potential first-in-class connective tissue growth factor inhibitor antibody did not meet its primary endpoint in a phase 3 trial for ambulator Duchenne muscular dystrophy.
In recent news, topline data from the phase 3 LELANTOS-2 trial (NCT04632940) showed that pamrevlumab (FibroGen) in combination with systemic corticosteroids failed to improve ambulatory function in ambulatory patients with Duchenne muscular dystrophy (DMD).1 FibroGen announced that they are in the process of assessing the totality of the data in order to decide the next steps and plan to communicate the full results of the study at an upcoming medical forum.
From baseline to week 52, the treatment did not meet the primary end point of change in North Star Ambulatory Assessment (NSAA) total score (placebo-corrected mean difference -0.528 points; 95% CI, -2.308 to 1.251; P = .5553). The secondary end points, change from baseline at week 52 in 4-stair climb velocity, 10-meter walk/run test, time to stand, time to loss of ambulation, and proportion of patients with greater than 10 seconds in the 10-meter walk/run test, were also not met.
“We are deeply disappointed that the LELANTOS-2 study did not meet its primary endpoint,” Thane Wettig, interim chief executive officer at FibroGen said in a statement.1 “We are grateful for the courageous efforts of patients, their caregivers, the advocacy community, and the trial investigators who have contributed to this important clinical study. We are committed to sharing all learnings from this trial with the Duchenne community and hope that there are insights that may help future efforts to develop treatments for this devastating disease.”
LELANTOS-2 was a global, phase 3, randomized, double-blind trial that investigated pamrevlumab or placebo plus systemic corticosteroids. There were a total of 73 patients with ambulatory DMD, ranging between the ages of 6 and 12 years, enrolled in the study. The primary end point of the trial was ambulatory function measured by change in the NSAA total score from baseline to week 52. The participants enrolled were dosed with pamrevlumab (35 mg/kg IV on day 1 and every 2 weeks thereafter with last dose at week 52) or placebo.
Although the preliminary safety data revealed that pamrevlumab was generally safe and well tolerated, treatment-emergent serious adverse events were reported in 8.3% of patients on the agent and 2.8% of patients in the placebo group. The majority of treatment emergent adverse events reported by patients with DMD were mild or moderate.
In June 2023, FibroGen reported similar news from its phase 3 LELANTOS-1 (NCT04371666) trial, which explored the effects of pamrevlumab plus systemic corticosteroid in nonambulatory patients with DMD. All told, that trial also failed to meet its primary end point in showing meaningful improvements in the Performance of the Upper Limb 2.0 score compared with baseline.2 A total of 92 male participants aged 12 and older were enrolled in the double-blind, placebo-controlled study that lasted a 52-week treatment period.
Participants received 35 mg/kg of the antibody or placebo intravenously every 2 weeks plus oral corticosteroid for the year-long study, at which point they could be rolled over into an open-label extension. Beyond the primary end point, participants were also evaluated on change from baseline in percent predicted forced vital capacity, grip strength of the hands, left ventricular ejection fraction percentage, and percent predicted peak expiratory flow, all assessed at 52 weeks.
Pamrevlumab, a potential first-in-class antibody, was developed to inhibit the activity of connective tissue growth factor (CTGF). CTGF is a common factor in fibrotic and proliferative disorders identified by persistent and excessive scarring that can lead to organ dysfunction and failure. In April 2019, the FDA granted orphan drug designed to pamrevlumab for treatment of patients with DMD.3 Following in April 2021, the treatment was granted fast track designation and Rare Pediatric Disease Designation by the FDA for the treatment of patients with DMD.4,5