The trial is set to read out topline data in the second half of 2023 after completing the target enrollment of 73 patients with Duchenne muscular dystrophy aged 6 to 12 years. The connective tissue growth factor inhibitor has been granted orphan drug, fast track, and rare pediatric disease designations.
FibroGen has announced that it has completed the target enrollment for its ongoing phase 3 LELANTOS-2 clinical trial (NCT04632940) of pamrevlumab, a first-in-class connective tissue growth factor (CTGF) inhibitor antibody, in patients with Duchenne muscular dystrophy (DMD).1
The trial was initiated in March 2021 as a follow-up to the first phase 3 trial, LELANTOS-1 (NCT04371666), to complete the 2-trial development plan.2 In April 2019, the FDA granted pamrevlumab an orphan drug designation for the treatment of DMD,3 and then followed up with rare pediatric disease and fast track designations in April 2021.4,5
In total, this second phase 3 trial includes 73 ambulatory patients with DMD aged 6 to 12 years, who are randomly assigned to either intravenous pamrevlumab 35 mg/kg, dosed every 2 weeks, plus systemic deflazacort (Emflaza; PTC Therapeutics) or equivalent potency of oral corticosteroids; or matching placebo plus systemic deflazacort or equivalent potency of oral corticosteroids. The study’s primary end point is ambulatory function assessment, defined as the change in North Star Ambulatory Assessment (NSAA) score from baseline to Week 52.
FibroGen noted in its announcement that topline data from LELANTOS-2 are anticipated to come in the second half of 2023. Mark Eisner, MD, MPH, the chief medical officer of FibroGen, expressed the company’s pleasure with achieving its enrollment goal in a statement,1 adding that, “pediatric patients living with DMD have limited treatment options, and LELANTOS-2 will evaluate pamrevlumab as a potential new treatment. On behalf of the entire study team, we would like to extend our gratitude to the patients, caregivers, investigators, and study staff for commitment to this study.”
Elias Kouchakji, MD, senior vice president of clinical development, drug safety, and pharmacovigilance at FibroGen, said in a statement at the time of LELANTOS-2’s initiation, that kicking off the study “underscores our commitment to delivering a meaningful treatment for DMD, an area with a high unmet medical need,” additionally highlighting that “Duchenne, the most common form of muscular dystrophy in children, is typically diagnosed by 2 to 6 years of age and progresses rapidly, resulting in the loss of independent motor function by the early teenage years.”2
In October 2020, shortly after the announcement of LELANTOS-1, Kouchakji, told NeurologyLive® that although ambulatory DMD space has many trials, including those with gene therapies, ongoing, that, “We should not dismiss the possibility of working against antifibrotic effects and whether they can delay earlier and minimize any of the formation of the fibrosis. In the end, I think it is still about a multitherapy for DMD, not a single therapy. We’ve done this in oncology. A long time ago, when we used to use a single type of toxic, we would start to see it work but only for a short period of time. Little by little we started to create a protocol of combination of chemotherapies which resulted in the improved survival and an increased cure rate.”
The news of the LELANTOS-2 trial’s enrollment completion follows similar news from April 2022 about pamrevlumab in another phase 3 clinical trial, ZEPHYRUS-1 (NCT03955146), which is evaluating the CTGF inhibitor in 356 individuals with idiopathic pulmonary fibrosis (IPF).6 The primary end point of ZEPHYRUS-1 is the change from baseline in forced vital capacity, with topline data expected to read out just before LELANTOS-2’s data, in mid-2023. FibroGen is also currently enrolling patients with IPF for the second phase 3 clinical trial in that development program, ZEPHYRUS-2 (NCT04419558).