US-based Gossamer Bio revealed that its pipeline candidate seralutinib, an inhaled PDGFR/CSF1R/c-KIT inhibitor, has failed to achieve the primary endpoint in a Phase III study assessing the molecule as a treatment for pulmonary arterial hypertension (PAH). Despite improving the 6-minute walk distance (6MWD) at week 24 of treatment by +13.3 meters over placebo, that did not meet the prespecified statistical significance threshold. As a result, p-values for key secondary endpoints were also not calculable under the trial’s hierarchical testing framework.

The PROSERA Study was a double-blind, placebo-controlled study that enrolled 390 patients with Class II or III PAH already heavily treated with background PAH therapy. According to Gosamer, the topline data suggests directionally favorable efficacy overall, noting stronger signals in prespecified higher-risk patients, and a generally tolerable safety profile consistent with prior experience. However, further analysis of the underlying data subsets will be carried out and enrolment in the ongoing SERANATA Study – assessing seralutinib in pulmonary hypertension associated with interstitial lung disease (PH-ILD) – will be paused. Gossamer indicated its plans to engage the US FDA regarding next steps.

Research context

Seralutinib is designed to inhibit platelet-derived growth factor receptor (PDGFR), colony stimulating factor 1 receptor (CSF1R), and c-KIT signaling pathways, which are implicated in vascular remodeling and inflammation in PAH. Unlike approved therapies that primarily target vasoconstriction through endothelin, nitric oxide, or prostacyclin pathways, seralutinib aims to directly address the proliferative and inflammatory drivers of pulmonary vascular remodeling, a central component of PAH pathobiology.

Key competitors targeting similar disease-modifying mechanisms in PAH include:

  • Merck’s sotatercept (Winrevair), an activin signaling inhibitor, which received US FDA approval based on Phase III STELLAR data; trial details are available via the NEJM publication.
  • Insmed’s inhaled treprostinil palmitil (TPIP), a next-generation prostacyclin prodrug currently in Phase II/III development for PAH, with study information available at ClinicalTrials.gov.
  • Altavant Sciences’ rodatristat ethyl, a peripheral tryptophan hydroxylase inhibitor targeting serotonin synthesis pathways in PAH, currently being evaluated in the Phase II ELEVATE 2 study as described in a company pipeline update.