MannKind's nintedanib DPI clears Phase 1b safety bar in IPF
MannKind Corporation has reported positive topline results from INFLO-1, its Phase 1b randomised, double-blind, placebo-controlled study of nintedanib dry powder inhalation (DPI) in patients with idiopathic pulmonary fibrosis (IPF). The Nasdaq-listed biopharmaceutical company said the study met its primary objective, demonstrating that the inhaled formulation was generally safe and well tolerated.
The trial enrolled 27 patients across 10 US sites and evaluated two multiple-ascending dose regimens administered over seven days. Key findings included no serious adverse events, no drug-related gastrointestinal side effects such as diarrhoea, nausea or vomiting, no bronchospasm events, and no treatment discontinuations or dose reductions. Spirometry parameters showed no differences between the nintedanib DPI and placebo arms, and 90% of patients experienced either no cough or only mild, transient episodes that resolved without intervention.
The clinical case for an inhaled formulation
The rationale behind MannKind's programme centres on a well-recognised limitation of the oral nintedanib standard of care. Approved oral nintedanib, marketed as Ofev by Boehringer Ingelheim, has a documented tolerability burden, most notably gastrointestinal side effects including diarrhoea in a significant proportion of patients. These events can drive dose reductions, treatment interruptions, or discontinuation, all of which limit the real-world effectiveness of an otherwise clinically validated agent.
MannKind is using its proprietary Technosphere dry powder inhalation platform, which already underpins two FDA-approved therapies, to deliver nintedanib directly to the deep lung. The company says the approach is intended to achieve therapeutic concentrations at the site of fibrotic disease while reducing systemic exposure. Across the completed Phase 1a first-in-human study in healthy volunteers and the INFLO-1 patient study, 48 individuals have now received nintedanib DPI, with more than 700 total inhalations on record.
Chief executive Michael Castagna said the results "provide growing confidence" as development moves into Phase 2, adding that cough was not a meaningful barrier to treatment in the IPF cohort.
Phase 2 INFLO-2 and the competitive backdrop
MannKind's global Phase 2 INFLO-2 study is already enrolling, targeting approximately 210 participants across around 85 sites worldwide. Participants will receive nintedanib DPI at either 2 mg four times daily or 4 mg twice daily, or placebo, for 12 weeks, followed by a 24-week open-label extension in which all will receive active treatment. The primary objective remains safety and tolerability, with secondary endpoints including the annualised rate of decline in forced vital capacity, a standard surrogate for disease progression in IPF.
The IPF landscape is competitive but not crowded at the inhaled-formulation frontier. Current approved therapies, oral nintedanib and pirfenidone, both carry tolerability concerns that have long prompted interest in alternative delivery approaches. Several academic and industry groups have explored inhaled antifibrotic strategies, but none has yet reached late-stage clinical development. If MannKind can replicate the clean tolerability profile seen in INFLO-1 at scale in INFLO-2, it would represent a meaningful differentiator in a market the American Lung Association estimates at 100,000 patients in the US alone, a figure that has risen roughly 20% over the past decade.
Full INFLO-1 data, including pharmacokinetic analyses, are expected to be presented at a future medical conference. Investors and clinicians will be watching the INFLO-2 safety readout and any early signal on FVC decline as the programme's next substantive catalysts.