Syndax axatilimab fails IPF primary endpoint in MAXPIRe Phase 2

Syndax Pharmaceuticals has reported that its CSF-1R-blocking monoclonal antibody axatilimab failed to meet the primary endpoint in the MAXPIRe Phase 2 trial in idiopathic pulmonary fibrosis (IPF), ending the company's ambitions in that indication. The company said it will not pursue further development of axatilimab in IPF.

MAXPIRe was a 26-week, randomised, double-blind, placebo-controlled study enrolling 145 patients across 62 sites in 14 countries. Patients were randomised two-to-one to receive axatilimab at 0.3 mg/kg or placebo every two weeks. The primary endpoint was the annualised rate of decline in forced vital capacity (FVC), a standard measure of disease progression in IPF. The trial did not demonstrate a statistically significant treatment effect on that measure.

On the safety side, the news was more encouraging. Axatilimab was well tolerated, with an adverse event profile described as comparable to placebo and no new safety signals identified. Rates of treatment-emergent adverse events leading to discontinuation were low in both arms, and there were no treatment-related fatal adverse events.

What this means for the axatilimab programme

Syndax is positioning the IPF setback as an isolated indication failure rather than a platform problem. Nick Botwood, Chief Medical Officer and Head of Research and Development, said the company was "disappointed by this outcome given the promising scientific rationale in IPF" but pointed to the drug's tolerability profile as support for its continued use in chronic graft-versus-host disease (cGVHD).

Axatilimab is already FDA-approved under the brand name Niktimvo for cGVHD in adult and paediatric patients following failure of at least two prior lines of systemic therapy. The drug is co-developed and co-commercialised with Incyte under a licensing agreement signed in September 2021. Two frontline combination trials are ongoing: a Phase 2 study pairing axatilimab with ruxolitinib and a Phase 3 trial combining it with steroids. Syndax expects data readouts from these trials later in 2026 and in early 2028, which will be the next significant test of the franchise's commercial ceiling.

Market and competitive context

IPF is a progressive, ultimately fatal lung disease with a median survival of two to five years from diagnosis. The approved standard of care consists of two antifibrotic agents, nintedanib and pirfenidone, both of which slow but do not halt progression. The unmet need has attracted a substantial wave of novel mechanism bets, including integrin inhibitors, LOXL2 inhibitors, and autotaxin inhibitors, many of which have also failed to demonstrate convincing efficacy in randomised trials. The biology of IPF has proven resistant to approaches that work well in inflammatory fibrosis settings, and the CSF-1R pathway's failure here is consistent with that broader pattern.

For Syndax, the immediate consequence is a narrowing of axatilimab's addressable market back to the haematological oncology and cGVHD space where the drug has performed more convincingly. Chief executive Michael Metzger reiterated focus on advancing both axatilimab and the company's menin inhibitor revumenib to frontline settings, framing the pipeline as carrying "multiple upcoming catalysts." Investors will weigh that optimism against the trial miss and watch closely for the cGVHD combination readouts to determine whether Niktimvo can achieve the blockbuster positioning the company is signalling.