Syndax Pharmaceuticals ends IPF development after Phase 2 axatilimab miss
The 145-patient MAXPIRe study missed its lung-function endpoint; safety was comparable to placebo and graft-versus-host disease trials continue.
Adrian Kessler
Development of axatilimab in idiopathic pulmonary fibrosis is ending after Syndax Pharmaceuticals, Inc. NASDAQSNDX reported on Monday that its Phase 2 MAXPIRe trial missed the annualized rate of decline in forced vital capacity endpoint.
The Oct. 12 release reported no arm-level lung-function figures, treatment effect, p value or confidence interval for the 145-patient study. Syndax said the outcome would not affect axatilimab trials in other indications, with chronic graft-versus-host disease readouts expected in the fourth quarter of 2026 and early 2028.
Syndax is a small-cap drug developer commercializing cancer therapies and a treatment for chronic graft-versus-host disease in the United States.
Syndax shares NASDAQSNDX closed at US$16.55, down 2.59 per cent, on Nasdaq at 4 p.m. EDT on Oct. 12. That close preceded the release's 4:01 p.m. EDT timestamp, so it does not measure the reaction to MAXPIRe.
The randomized, double-blind study compared axatilimab with placebo over 26 weeks. Patients were assigned two to one to receive the antibody at 0.3 milligrams per kilogram or placebo every two weeks, with assignment stratified by background antifibrotic treatment.
The primary measure annualized forced vital capacity, or FVC, decline over 52 weeks using measurements collected during the shorter treatment period. FVC measures the volume of air forcibly exhaled; the annualized endpoint was therefore an estimate derived from the trial's observed lung-function measurements.
Syndax reported a safety profile comparable to placebo, low treatment-discontinuation rates in both arms and no treatment-related fatal adverse events or new safety signals. The topline release did not describe FDA feedback on MAXPIRe's design.
"Axatilimab was well tolerated, with a safety profile consistent with prior studies supporting its continued development and use in cGVHD," Syndax head of research and development and chief medical officer Nick Botwood said in the release.
Rival Lung Programs Report Different Outcomes
Bristol Myers Squibb NYSEBMY reported on Oct. 12 that its Phase 3 ALOFT-IPF trial met its FVC endpoint with admilparant at 60 milligrams twice daily. The higher-dose arm, at 120 milligrams twice daily, slowed decline without reaching statistical significance.
ALOFT-IPF enrolled approximately 1,255 adults and measured absolute FVC change at week 52, a different design from MAXPIRe's annualized decline over shorter follow-up. Bristol Myers also withheld detailed efficacy figures in its topline announcement, preventing a numerical comparison between the programs.
Read more: Bristol Myers Squibb reports admilparant trial success as higher dose misses
Bristol Myers estimated in its Oct. 12 release that approximately 1.4 million people live with IPF globally. The disease involves irreversible lung scarring, and the company said existing treatments can slow lung-function decline while additional effective and tolerable therapies remain needed.
United Therapeutics Corporation NASDAQUTHR markets Tyvaso and Tyvaso DPI, which its Sept. 30 release identifies as approved for pulmonary hypertension associated with interstitial lung disease. That PH-ILD indication concerns pulmonary hypertension, a different treatment target from MAXPIRe's IPF objective.
Read more: United Therapeutics Corporation wins Yutrepia PH-ILD patent ruling
Commercial Sales And GVHD Trials Continue
Axatilimab, sold as Niktimvo, is already FDA-approved for chronic graft-versus-host disease after failure of at least two systemic treatment lines in adults and children weighing at least 40 kilograms. Syndax is studying it with ruxolitinib and with steroids in newly diagnosed disease.
Syndax's Aug. 4 financial update reported second-quarter Niktimvo net revenue of US$60.3 million, yielding US$18.1 million in collaboration revenue for Syndax. Its Oct. 12 trial-results section provided no updated cash-runway estimate.
The next axatilimab readouts are expected in the fourth quarter of 2026, followed by early 2028. Those results will test combination treatment in chronic graft-versus-host disease as the IPF program ends.
