MNKD-201, inhaled nintedanib for IPF, found safe in healthy people
Typical adverse events seen with oral therapy did not occur in Phase 1 trial
MNKD-201, Mannkind’s inhaled formulation of nintedanib for treating idiopathic pulmonary fibrosis (IPF), was found to be safe and well tolerated in a Phase 1 clinical trial involving healthy volunteers — meeting the study’s primary goal.
The trial’s results also showed that participants did not experience the typical adverse events seen with oral nintedanib, an approved IPF therapy sold as Ofev.
Based on these data, Mannkind plans to meet with the U.S. Food and Drug Administration (FDA) in the first half of 2025 to advance the therapy’s clinical development, the company said in a press release.
“These compelling results support advancing the development of nintedanib [dry powder inhaler (DPI)] for patients living with IPF, a chronic and progressive fibrotic lung disease with limited treatment options,” said Michael Castagna, Mannkind’s CEO.
Meeting with FDA on inhaled nintedanib formulation expected next year
Pulmonary fibrosis, or PF for short, is a respiratory disease caused by scarring, or fibrosis, in the lungs that makes it harder for patients to breathe. To function normally, lungs need to be stretchy so they can inflate and deflate as a person breathes. However, in PF, scar tissue causes the lungs to stiffen and not function properly. In IPF, the most common form of the disease, the underlying cause of lung scarring is not known.
Nintedanib is an inhibitor of tyrosine kinase, an enzyme essential for the production of growth factors that are excessively produced in IPF patients and contribute to the production of scar tissue. It is the active ingredient of Ofev, an antifibrotic therapy that’s widely approved to treat people with IPF and other types of interstitial lung diseases.
Despite its efficacy, Ofev can cause side effects, including gastrointestinal and liver problems, which can lead patients to discontinue treatment. To overcome these problems, Mannkind developed MNKD-201, a dry powder inhaled formulation of nintedanib that delivers the medication directly to the lungs.
According to Wassim Fares, Mannkind’s senior vice president and therapeutic area head of orphan lung diseases, this formulation may ultimately prove to be better for patients.
“Building on the known efficacy of oral nintedanib for IPF, delivery of a dry powder formulation directly to the lungs could potentially treat the disease while reducing the common adverse effects associated with oral delivery of nintedanib,” Fares said.
The therapy’s safety and tolerability were assessed in a Phase 1 trial (NCT06532942) in Texas. The study enrolled healthy adults, ages 40 and older. The participants were randomly assigned to receive single (24 people) or multiple (16 people) ascending doses of MNKD-201 or a placebo.
The study’s primary goal was to assess the safety and tolerability of MNKD-201, while secondary goals included evaluating the therapy’s pharmacological properties.
MNKD-201 was found to be safe and well tolerated at all doses tested during the study, without causing the typical adverse events seen with the oral formulation of nintedanib, such as gastrointestinal and neurologic effects.
Building on the known efficacy of oral nintedanib for IPF, delivery of a dry powder formulation directly to the lungs could potentially treat the disease while reducing the common adverse effects associated with oral delivery of nintedanib.
The most commonly reported adverse events seen with the inhaled formulation included cough and a decrease in lung function, assessed by the forced expiratory volume in one second (FEV1), which measures how much air a person can forcibly exhale in one second.
These adverse events were mild and transient, and not dose-dependent. Patients fully recovered from these events, without recurrence or worsening with repeated dosing, Mannkind stated.
Moreover, no symptoms like wheezing or bronchospasm — a tightening of the muscles around the airways, that can cause difficulty breathing — were reported. Likewise, no serious adverse events or cases of treatment discontinuation were described.
A preclinical chronic toxicology study also did not reveal any adverse findings, supporting the continued development of MNKD-201, according to Mannkind.
“Pending late-stage development trials, nintedanib DPI could offer an alternative and/or addition to current IPF therapies,” Fares said.
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