RARE Daily

Fibrogen Duchenne Candidate Fails in Phase 3 Study

August 30, 2023

Rare Daily Staff

FibroGen said its experimental therapy pamrevlumab failed to meet the primary and secondary endpoints in its phase 3 LELANTOS-2 trial for the treatment of ambulatory patients with Duchenne muscular dystrophy on background systemic corticosteroids.

The study used change in the North Star Ambulatory Assessment (NSAA) total score from baseline to week 52 as its primary endpoint. Secondary endpoints measured by 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 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,” said Thane Wettig, Interim CEO of FibroGen.

Duchenne muscular dystrophy (DMD) is a rare and debilitating neuromuscular disease that affects approximately 1 in every 5,000 newborn boys. About 20,000 children are diagnosed with DMD globally each year. The fatal disease is caused by a genetic mutation leading to the absence or defect of dystrophin, a protein necessary for normal muscle function. The absence of dystrophin results in muscle weakness, muscle loss, fibrosis, and inflammation. Patients with DMD are often wheelchair-bound before the age of 12, and their progressive muscle weakness may lead to serious medical problems relating to respiratory and cardiac muscle.

Pamrevlumab is a potential first-in-class antibody being developed by FibroGen to inhibit the activity of connective tissue growth factor (CTGF), a common factor in fibrotic and proliferative disorders characterized by persistent and excessive scarring that can lead to organ dysfunction and failure.

Pamrevlumab is in phase 3 clinical development for the treatment of ambulatory DMD, and locally advanced unresectable pancreatic cancer (LAPC), and in phase 2/3 for the treatment of metastatic pancreatic cancer.

The U.S. Food and Drug Administration has granted Orphan Drug designation to pamrevlumab for treatment of patients with DMD and pancreatic cancer, and Fast Track designation to pamrevlumab for the treatment of patients with DMD and LAPC. The FDA has also granted Rare Pediatric Disease designation to pamrevlumab for the treatment of patients with DMD.

Pamrevlumab has demonstrated a safety and tolerability profile that has supported ongoing clinical investigation in DMD, LAPC, and metastatic pancreatic cancer. Pamrevlumab is an experimental drug and not approved for marketing by any regulatory authority.

Preliminary safety data showed that pamrevlumab was generally safe and well tolerated. The majority of treatment emergent adverse events were mild or moderate. Treatment-emergent serious adverse events were observed in 8.3 percent of patients in the pamrevlumab group and 2.8 percent of patients in the placebo group.

FibroGen said it is evaluating the totality of the data, including other pre-specified endpoints, to determine the next steps for the program. The company plans to communicate the full results of the LELANTOS-2 study at an upcoming medical forum.

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