Pamrevlumab fails to slow lung decline in ZEPHYRUS-1 IPF trial
ZEPHYRUS-2, a similar Phase 3 trial into pamrevlumab's use, to stop
A Phase 3 trial of pamrevlumab, an experimental therapy from FibroGen to treat idiopathic pulmonary fibrosis (IPF), failed to meet its primary goal of slowing lung function decline.
General safety and tolerability were seen in treated patients in ZEPHYRUS-1 (NCT03955146), which tested 48 weeks of pamrevlumab’s use against a placebo. A second trial goal of slower disease progression also was not met.
Based on these results, the company will stop testing in ZEPHYRUS-2 (NCT04419558), a similar and fully enrolled Phase 3 study of pamrevlumab in IPF patients.
“We are deeply disappointed that these results do not support pamrevlumab as a new treatment for IPF,” Mark D. Eisner, MD, chief medical officer at FibroGen, said in a company press release. “FibroGen would like to thank the patients and clinical trial investigators for their dedication to participating in this study.”
Pamrevlumab failed to significantly improve FVC in treated IPF patients
Pamrevlumab, an antibody, is designed to bind to and block the action of connective tissue growth factor (CTGF), a protein that drives the fibrosis, or scar tissue formation, that marks pulmonary fibrosis. By blocking CTGF activity, pamrevlumab was expected to reduce the buildup of scar tissue and ease disease symptoms.
Conducted at more than 100 sites worldwide, ZEPHYRUS-1 enrolled 356 patients who were not using any approved PF treatment for reasons ranging from lack of response or tolerability to patient choice.
They were randomized to an intravenous infusion of pamrevlumab at a dose of 30 mg/kg or a placebo every three weeks, for a total of up to 17 infusions over the study’s 48 weeks.
Its primary endpoint was changes with treatment in forced vital capacity (FVC), which measures the total amount of air a person can exhale after a deep breath, from the study’s start (baseline) to week 48. A decline in FVC is an indicator that lung function is deteriorating and IPF is progressing.
The mean decline in FVC at week 48 was 260 mL in the pamrevlumab group and 330 mL in the placebo group, which favored pamrevlumab but was not large enough to be considered statistically significant. In other words, pamrevlumab did not significantly slow lung function decline in IPF patients.
The secondary goal of time to disease progression, defined as a decline in FVC percent predicted of 10% or more or a patient’s death, also was not met.
Pamrevlumab was generally safe, with most treatment-related side effects being mild or moderate. Serious side effects occurred in about the same proportion of patients in the pamrevlumab and placebo groups (28.2% vs. 34.3%).
Further details were not given in the release. The company plans to share fuller trial results at a future medical meeting.
Pamrevlumab is also being tested in boys with Duchenne muscular dystrophy who are able to walk. Top-line data from the Phase 3 LELANTOS-2 (NCT04632940) trial are expected later this year. Two other Phase 3 pamrevlumab studies are underway for locally advanced and metastatic pancreatic cancer.
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