MannKind (NASDAQ:MNKD) reported Phase 1b results for its inhaled nintedanib dry-powder inhalation, or DPI, candidate in patients with idiopathic pulmonary fibrosis, or IPF, saying the seven-day study met its objective of demonstrating short-term safety and tolerability.
The company’s INFLO-1 trial was a randomized, double-blind, placebo-controlled Phase 1b study involving 27 IPF patients at 10 U.S. sites. Participants received one of two active treatment regimens or placebo, with dose escalation subject to reviews by MannKind and an external Data and Safety Monitoring Board.
Focus on Tolerability in Fibrotic Lungs
The study was designed to assess whether repeated administration of inhaled nintedanib could be tolerated by patients with fibrotic lungs, rather than to establish efficacy. Fares said the study showed no difference in spirometry between patients receiving active drug and those receiving placebo, which used an empty cartridge.
Cough was a key focus of the update. MannKind said about 60% of patients who received active treatment had no cough reported as an adverse event. Of the remaining patients, approximately 30% experienced mild, or Grade 1, cough and 10% experienced moderate cough. No patients reported severe cough.
Fares said the cough events were deemed treatment-related, generally occurred after the first inhalation and were mostly transient. Patients with baseline cough did not experience worsening cough if no cough adverse event was reported, he said. The company also said it identified no baseline characteristic or disease-severity trend that predicted which patients would experience cough, though it noted the study sample was small.
Chief Executive Officer Michael Castagna said the company views the first week of treatment as particularly relevant for evaluating powder-related cough. He said MannKind’s prior experience with its Technosphere dry-powder platform indicates cough generally appears early and declines over continued treatment, though longer-term data will be needed to confirm the profile in IPF.
Inhaled Delivery Strategy
Nintedanib is an established oral anti-fibrotic therapy for IPF, but MannKind is developing an inhaled version intended to deliver the drug to the lung while limiting gastrointestinal exposure and systemic adverse effects.
Fares said preclinical studies found lung concentrations at least 100 times higher than plasma concentrations, with minimal systemic exposure. The company also cited previously released data from a first-in-human healthy-volunteer study, which evaluated single doses of 2 to 8 milligrams and repeat twice-daily dosing over seven days. MannKind said that study showed no serious adverse events or discontinuations, while mild reversible cough was observed mainly after the first dose.
In discussing pharmacokinetics, Fares said plasma concentrations can serve as a surrogate for drug delivery to deep lung tissue because inhaled nintedanib must pass through the lung before entering the bloodstream. MannKind said its DPI formulation produced plasma peak concentrations approximately six to eight times higher than published values for a nebulized nintedanib formulation at comparable doses. Fares cautioned that the comparison was across separate studies and was not head-to-head.
Phase 2 Trial Underway
MannKind has begun enrolling patients in INFLO-2, a global, randomized, double-blind, placebo-controlled Phase 2 study expected to enroll 210 people with IPF. The study includes a 12-week controlled period comparing two active regimens with matched placebo, followed by a 24-week open-label extension.
The primary objective is safety and tolerability, with forced vital capacity, or FVC, serving as the key efficacy endpoint. The trial will include untreated patients as well as patients on stable background therapy with pirfenidone and/or Jascayd, according to the company. Patients may have previously used oral nintedanib but cannot be actively taking it in the trial.
- One treatment regimen is 4 milligrams twice daily.
- The second regimen is 2 milligrams four times daily.
- MannKind said it does not currently expect meaningful tolerability differences between the regimens, while the study will evaluate potential efficacy differences.
Castagna said MannKind expects enrollment activity to increase through 2026 and is assessing ways to accelerate the program. He characterized the Phase 1b results as a clinical de-risking step, while acknowledging that the data do not establish long-term safety, efficacy or commercial success.
The company said it has built patent protection for nintedanib DPI and combination uses extending to 2046. Castagna said MannKind sees potential for the therapy as an alternative for patients unable to tolerate oral nintedanib and as a possible component of future combination regimens, contingent on results from the ongoing clinical program.
About MannKind (NASDAQ:MNKD)
MannKind Corporation, a biopharmaceutical company, focuses on the development and commercialization of inhaled therapeutic products for endocrine and orphan lung diseases in the United States. It offers Afrezza, an inhaled insulin used to improve glycemic control in adults with diabetes, and the V-Go wearable insulin delivery device, which provides continuous subcutaneous infusion of insulin in adults. The company's product pipeline also includes Tyvaso DPI (Treprostinil), an inhalation powder for the treatment of pulmonary arterial hypertension and pulmonary hypertension associated with interstitial lung disease; MNKD-101, a nebulized formulation of clofazimine, for the treatment of severe chronic and recurrent pulmonary infections, including nontuberculous mycobacterial lung disease; MNKD-201, a dry-powder formulation of nintedanib, for the treatment of idiopathic pulmonary fibrosis (IPF).
