Deupirfenidone reduces FVC decline, well tolerated in IPF at 26 weeks
Key takeaways:
- Two differing doses of deupirfenidone were assessed against placebo.
- Researchers deemed them as being “generally well tolerated.”
- The 825 mg deupirfenidone group had a significantly smaller degree of FVC decline.
Patients with idiopathic pulmonary fibrosis had less FVC decline between baseline and 26 weeks with receipt of three daily doses of 825 mg deupirfenidone, according to phase 2b ELEVATE IPF trial results.
“The efficacy seen with the 825 mg dose of deupirfenidone was certainly better than we dared expect,” Toby M. Maher, MD, PhD, professor of medicine and director of interstitial lung disease at Keck School of Medicine, University of Southern California, Los Angeles, told Healio. “The data provide the hope that it will be possible to improve outcomes for people living with IPF whilst at the same time reducing the side effect burden associated with treatment.”
In this randomized, double-blind, active- and placebo-controlled, dose-ranging phase 2b study, Maher and colleagues assessed 257 patients with IPF to determine the impact of two differing doses of deupirfenidone (LYT-100, PureTech) — 825 mg three times per day and 550 mg three times per day — and 801 mg pirfenidone three times per day vs. placebo on FVC at 26 weeks.
According to the release, 65 patients received 550 mg deupirfenidone, 64 patients received 825 mg deupirfenidone, 63 patients received 801 mg pirfenidone and 65 patients received placebo.
Between baseline and 26 weeks, researchers observed that patients in the 825 mg deupirfenidone group had a significantly smaller degree of FVC decline vs. patients in the placebo group (–21.5 mL vs. –112.5 mL; P = .02).
Similarly, a smaller FVC reduction at the 26-week mark was found in the 801 mg pirfenidone group vs. the placebo group (–51.6 mL vs. –112.5 mL), according to the release.
Based on the comparisons above, researchers highlighted that those receiving 825 mg deupirfenidone had a greater treatment effect than those receiving 801 mg pirfenidone (80.9% vs. 54.1%).
The baseline to week 26 change in FVC was not significant when the 550 mg deupirfenidone group was placed against the placebo group, but researchers did report less FVC decline with deupirfenidone (–80.7 mL vs. –112.5 mL).
In addition to FVC, the release said that the change in percent-predicted FVC between baseline and the 26-week mark was –0.43 among those receiving 825 mg deupirfenidone, which was significantly better than the change of –3.43 observed among those receiving placebo (P = .01).
During the safety analysis, researchers deemed the 825 mg and 550 mg deupirfenidone doses as being “generally well tolerated.”
For five key gastrointestinal adverse events, fewer patients in the 825 mg deupirfenidone group vs. the 801 mg pirfenidone group experienced them. According to the release, these events included “nausea (20.3% vs. 27%), dyspepsia (14.1% vs. 22.2%), diarrhea (7.8% vs. 11.1%), constipation (4.7% vs. 6.3%) and vomiting (1.6% vs. 3.2%).”
Notably, a higher proportion of patients receiving this dose of deupirfenidone reported abdominal pain (14.1% vs. 7.9%).
Death occurred in each group (825 mg and 550 mg deupirfenidone, n = 1 each; pirfenidone, n = 5; placebo, n = 2), and the release said none had been classified as related to the given treatment.
“This was a phase 2b study so there will be no immediate impact on the treatment of patients,” Maher told Healio. “But everyday clinicians recognize the huge unmet need for better treatments for fibrotic lung disease; these findings provide the promise of more effective and better tolerated treatment in the near future.
“PureTech has stated that they are committed to continuing development of deupirfenidone, and I am very enthusiastic about the continued development of this program,” Maher added.
There is currently an ongoing open-label extension trial involving 170 patients of the 187 who completed this trial, and the release says it supports what has been outlined above for the 825 mg dose of deupirfenidone based on preliminary data.
According to the release, clinicians can expect to see more trial data at a future forum.