ELEVATE-IPF: New Findings on Deupirfenidone

Key Takeaways

• ELEVATE-IPF randomized patients to deupirfenidone 550 mg, deupirfenidone 825 mg, pirfenidone 801 mg, or placebo.
• Less FVC decline was reported for combined deupirfenidone versus placebo, and a separate frequentist analysis also reported less decline for deupirfenidone 825 mg versus placebo.
• Gastrointestinal events were the most common adverse events in active arms.

Researchers randomized 257 patients in a 1:1:1:1 ratio to deupirfenidone 550 mg three times daily, deupirfenidone 825 mg three times daily, pirfenidone 801 mg three times daily, or placebo. The prespecified primary endpoint assessed whether the combined deupirfenidone groups had a slower 26-week rate of forced vital capacity decline than placebo.

Investigators reported the primary analysis as a Bayesian comparison of the 26-week rate of change in forced vital capacity for the combined deupirfenidone arms versus placebo. The placebo group had a posterior mean change of -110.71 mL, while the combined deupirfenidone groups had a posterior mean change of -48.42 mL. Researchers reported a posterior mean difference of 62.29 mL (95% credible interval, −6.13 to 115.73), with a posterior probability of 0.985. Over 26 weeks, the combined deupirfenidone analysis showed less decline than placebo.

A separate frequentist analysis was reported for the deupirfenidone 825 mg arm versus placebo. Adjusted mean forced vital capacity change was -112.5 mL for placebo and -21.5 mL for deupirfenidone 825 mg. Investigators also observed an adjusted mean difference of 91.0 mL (95% CI, 12.2 to 169.7), with P = .02. The higher-dose deupirfenidone arm was reported to have a smaller FVC decline than placebo. While the primary Bayesian analysis suggested a high probability of benefit, only the frequentist analysis of the 825 mg dose demonstrated statistical significance.

The trial also reported treatment persistence through study end at 80.0% with placebo, 68.3% with pirfenidone, 64.6% with deupirfenidone 550 mg, and 78.1% with deupirfenidone 825 mg. Authors noted gastrointestinal adverse events as the most common events in each active-treatment arm over 26 weeks.