FibroGen Begins Phase 3 Trial of Pamrevlumab for IPF

A fully recombinant human monoclonal antibody therapy has begun phase 3 assessment for the treatment of idiopathic pulmonary fibrosis (IPF).

Pamrevlumab, a connective tissue growth factor (CTGF) inhibitor, is now being dosed in patients with IPF participating in the ZEPHYRUS-2 phase 3 trial.

Previously evidenced to attenuate the progressive and potentially fatal symptoms of IPF, the agent developed by FibroGen could indicate a novel pathway of care.

The drug

The first-in-class monoclonal antibody’s benefit for patients with IPF is based on its inhibition of CTGF, a common driver of fibrotic and cancerous conditions.

As such, the agent is current in clinical assessment for the treatment of various diseases: IPF, locally advanced unresectable pancreatic cancer, Duchenne muscular dystrophy, and coronavirus 2019 (COVID-19).

In previously FibroGen-funded, double-blind, placebo-controlled, phase 2 research, 30 mg/kg pamrevlumab every 3 weeks was associated with reductions in disease progression risk (10.0% vs 31.4%; P = .013) at 48 weeks, and reduced decline in percentage of predicted forced vital capacity (FVC) by more than 60% in the same time period among patients with IPF.

The US Food and Drug Administration (FDA) granted Fast Track Designation to FibroGen for the treatment of patients with IPF in September 2018.

The trial

Pamrevlumab is being assessed in a phase 3 clinical development program consisting of a pair of studies (ZEPHYRUS, ZEPHYRUS-2) evaluating the agent’s efficacy and safety in patients with IPF over 52 weeks.

ZEPHYRUS is an ongoing randomized, double-blind, placebo-controlled study with a primary endpoint of FVC change from baseline.

ZEPHYRUS-2 will observe pamrevlumab versus placebo in approximately 340 patients with IPF previously treated with an approved, but now discontinued therapy for their condition. Investigators are assessing for a primary endpoint of disease progression per FVC percent predicted decline ≥10%, or death. Key secondary endpoints will include quantitative lung fibrosis (QLF) change, and patient-reported outcomes.

Participants to complete the 52-week trial will be eligible for an open-label extension assessment of the therapy via rollover.

Clinical impact

Further results indicating pamrevlumab’s benefit for attenuated IPF progression would contribute to an at-need chronic patient population who generally face a burden of symptoms and reduced life expectancy.

On average, patients are estimated to have a life expectancy of 3-5 years from IPF diagnosis, with about two-thirds dying within that time span.

In general, pulmonary fibroses are met with few available therapies and a burden of patient unawareness. A 2020 survey from the Pulmonary Fibrosis Foundation (PFF) showed more than half of surveyed US adults weren’t familiar with the chronic lung condition’s symptoms and effects.

And, as highlighted in an HCPLive® interview with PFF chief medical officer Greg Cosgrove, the first randomized, controlled clinical trial conducted for pulmonary fibrosis care took place only 2 decades ago.

Nonetheless, in that short time frame, investigative agents with novel pathways have emerged as promising contributors to pulmonary fibrosis management, Cosgrove said.

“What it’s really telling me is that the way in which we can impact and treat patients, there’s not just a therapy, or 2—there are multiple different therapies that might be of benefit if we can appropriately evaluate them,” he explained. “The ultimate goal going forward is having what we call precision medicine, where we have the best treatments for the individual patient.”

As noted by Elias Kouchaki, MD, FibroGen senior vice president of Clinical Development and Drug Safety, disease-modifying therapies are “urgently needed” in the space.

“We are excited to advance the Phase 3 clinical development program for pamrevlumab, a first-in-class antibody which represents a novel approach to the treatment of IPF, a disease with survival rates comparable to those of some of the deadliest cancers,” Kouchaki said in a statement.

FibroGen chief medical officer Mark Eisner, MD, MPH, highlighted the advancement of research into CTGF—and as such, the improved understanding of fibrotic and proliferative disorders.

“We are committed to advancing the science of CTGF biology and evaluating clinical benefit in diverse diseases with unmet medical need, including IPF, locally advanced unresectable pancreatic cancer and Duchenne muscular dystrophy,” Eisner said.