MannKind Provides Update on Phase 3 ICoN-1 Trial of Nebulized Clofazimine for NTM Lung Disease

Rhea-AI Summary

MannKind (Nasdaq: MNKD) announced discontinuation of the Phase 3 ICoN-1 trial of MNKD-101, a nebulized clofazimine inhalation suspension, after a futility determination.

An interim analysis of sputum culture conversion in the first 46 participants showed no conversions, and an ad hoc meeting on Nov 8, 2025 led the independent DSMB to agree to stop the trial for futility; the DSMB reported no safety concerns.

The outcome does not affect development of MNKD-102, a dry powder inhalation (DPI) clofazimine formulation progressing toward Phase 1 development. MannKind will host a conference call today at 9:00 AM EST with a webcast and a replay available for ~90 days.

Positive

• Independent DSMB reported no safety concerns
• MNKD-102 DPI remains in development toward Phase 1

Negative

• ICoN-1 Phase 3 of MNKD-101 discontinued due to futility
• No sputum culture conversions in first 46 participants
• Nebulized MNKD-101 failed to show efficacy signal in trial

Insights

Clinical-Business Analyst

Phase 3 ICoN-1 was stopped for futility after no sputum culture conversions; safety signals were absent; DPI program remains under consideration.

As reported, the independent DSMB recommended discontinuation after an ad hoc review on November 8, 2025 because the first 46 participants who completed the double‑blind phase showed no sputum culture conversions, undermining the likelihood of meeting the trial’s primary endpoint. The decision reflects an efficacy failure for the nebulized formulation (MNKD‑101) rather than a safety issue, since the DSMB did not identify safety concerns at any point.

The immediate business impact concentrates on development pivoting: MNKD‑101’s regulatory and commercial prospects are effectively halted by this futility finding, while the dry powder inhalation candidate, MNKD‑102, is explicitly stated to be unaffected and is described as progressing toward Phase 1. Key dependencies and risks are straightforward and fact‑based: confirmation of why the nebulized formulation failed (pharmacokinetics, delivery, or formulation) will determine whether learnings apply to MNKD‑102, but no assertions about cause are provided in the release.

Concrete items to watch in the near term include the company’s conference call today at 9:00 AM EST for management’s explanation, any data they disclose about the sputum culture analysis, and updates on MNKD‑102’s planned Phase 1 timing or study design. Over the next 1–6 months, look for internal analyses clarifying whether the nebulized route or other factors drove the lack of conversions, and for specific milestones or protocol files for MNKD‑102.

• MannKind has made the decision to discontinue the ICoN-1 Phase 3 clinical trial evaluating nebulized clofazimine inhalation suspension for nontuberculous mycobacterial (NTM) lung disease, following a futility determination based on medical monitoring data
• This outcome does not impact the development of MNKD-102, MannKind’s dry powder inhalation (DPI) formulation of clofazimine, which remains under consideration for future clinical advancement
• MannKind extends its sincere gratitude to the study participants, investigators, advisors, and clinical site teams for their invaluable contributions to the ICoN-1 study
• MannKind will host a conference call today at 9:00 AM EST to discuss this update in more detail

DANBURY, Conn. and WESTLAKE VILLAGE, Calif., Nov. 10, 2025 (GLOBE NEWSWIRE) -- MannKind Corporation (Nasdaq: MNKD) today announced the discontinuation of its Phase 3 ICoN-1 clinical trial evaluating MNKD-101, a nebulized clofazimine inhalation suspension, for the treatment of refractory nontuberculous mycobacterial (NTM) lung disease.

As part of routine study monitoring and in accordance with the trial protocol, an analysis was conducted on sputum culture conversion data from the first 46 participants who completed the double-blind treatment phase. No conversions were observed, prompting concerns regarding the likelihood of achieving the study’s key primary endpoint. Following an ad hoc meeting held on November 8, 2025, the independent Data Safety Monitoring Board (DSMB) reviewed the data and agreed with the decision to discontinue the trial due to futility. Importantly, the DSMB did not identify any safety concerns at any point during the study.

“We are disappointed that the nebulized formulation did not demonstrate efficacy in this patient population,” said Dr. Ajay Ahuja, Chief Medical Officer of MannKind Corporation. “However, we remain hopeful regarding the potential of MNKD-102, our dry powder inhalation (DPI) formulation of clofazimine, which has been progressing toward Phase 1 development. We are committed to understanding the factors that contributed to this outcome in the nebulized formulation and applying those insights to guide our future development efforts.”

MannKind extends its deep appreciation to the study participants, investigators, clinical site teams, and all stakeholders who contributed to the ICoN-1 study and continue to support the advancement of therapies for NTM lung disease.

Conference Call
MannKind will host a conference call and presentation webcast to discuss these findings today at 9:00 a.m. Eastern Standard Time. The webcast will be accessible via a link on MannKind’s website. A replay will also be available in the same location within 24 hours after the call and accessible for approximately 90 days.

About the ICoN-1 Clinical Trial
The ICoN-1 trial is a multi-national, randomized, double-blind, placebo-controlled, Phase 3 registrational study to evaluate the efficacy and safety of clofazimine inhalation suspension for nebulized inhalation when added to guideline-based therapy in adults with refractory NTM lung disease caused by mycobacterium avium complex (MAC), followed by an open-label extension. The co-primary endpoints in the U.S. are sputum culture conversion (negative for NTM for 3 consecutive months) from baseline to end of Month 6 and change in quality of life (QoL) during the same timeframe. Outside the U.S., the primary endpoint is sputum culture conversion.

About NTM – A Global Health Concern
Pulmonary NTM infection is a rare disease with a global health impact due to its rising prevalence worldwide and association with shortened life span, high morbidity, and significant impact on patients’ quality of life. NTM is a group of bacteria naturally found in our environment, including water and soil, that can lead to cough, fatigue, a reduction in lung function, and poor quality of life among other debilitating symptoms. While most people are exposed to NTM daily, the organisms generally do no harm. Individuals with underlying conditions such as COPD, asthma, and bronchiectasis are at increased risk of NTM getting established in the lungs creating an infection and progressive worsening of lung function.

There are nearly 200 species of NTM; the most common is MAC, which accounts for about 80% of all NTM lung disease cases in the United States. While not everyone is at risk of contracting NTM from MAC, for those who are, it can cause serious lung damage. NTM lung disease is more common in women over the age of 65. Estimated 2022 NTM disease prevalence is more than 100,000 in the U.S. and over 150,000 in Japan. Approximately 15-20% of NTM patients are refractory. The prevalence rate of NTM is increasing globally – within the U.S. alone claims-based studies suggest an annual rise of 7.5%. To learn more about NTM, please visit LearnAboutNTM.com.

About MannKind
MannKind Corporation (Nasdaq: MNKD) is a biopharmaceutical company dedicated to transforming chronic disease care through innovative, patient-centric solutions. Focused on cardiometabolic and orphan lung diseases, we develop and commercialize treatments that address serious unmet medical needs, including diabetes, pulmonary hypertension, and fluid overload in heart failure and chronic kidney disease.

With deep expertise in drug-device combinations, MannKind aims to deliver therapies designed to fit seamlessly into daily life.

Learn more at mannkindcorp.com.

Forward-Looking Statements
Statements in this press release that are not statements of historical fact are forward-looking statements that involve risks and uncertainties. These statements include, without limitation, statements regarding MannKind's plan to investigate the causes for the failure of MNKD-101 to produce sputum culture conversion and to apply its findings to the development of MNKD-102. Words such as “believes,” “anticipates,” “plans,” “expects,” “intends,” “will,” “goal,” “potential,” and similar expressions are intended to identify forward-looking statements. These forward-looking statements are based upon MannKind’s current expectations. Actual results and the timing of events could differ materially from those anticipated in such forward-looking statements as a result of various risks and uncertainties, which include, without limitation, risks associated with developing product candidates; risks and uncertainties related to unforeseen delays that may impact the timing of clinical trials and reporting data; and other risks detailed in MannKind’s filings with the Securities and Exchange Commission (“SEC”), including under the “Risk Factors” heading of its most recently filed Quarterly Report on Form 10-Q. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date of this press release. All forward-looking statements are qualified in their entirety by this cautionary statement, and MannKind undertakes no obligation to revise or update any forward-looking statements to reflect events or circumstances after the date of this press release.

MANNKIND is a registered trademark of MannKind Corporation.

MannKind Contacts:
Media Relations
Christie Iacangelo, (818) 292-3500
Email: media@mnkd.com

FAQ

Why did MannKind (MNKD) discontinue the Phase 3 ICoN-1 trial on Nov 10, 2025?

An interim analysis of the first 46 participants showed no sputum culture conversions, and the independent DSMB agreed to stop the trial for futility.

Did the DSMB report any safety issues in the ICoN-1 trial for MNKD (MNKD)?

No; the DSMB did not identify any safety concerns at any point during the study.

How does the ICoN-1 discontinuation affect MannKind’s MNKD-102 development (MNKD)?

MannKind said the ICoN-1 outcome does not impact MNKD-102, which is progressing toward Phase 1 development.

When is MannKind’s conference call to discuss the ICoN-1 update (MNKD)?

The company will host a conference call and webcast today at 9:00 AM EST with a replay available afterward.

What specific efficacy data triggered stopping the ICoN-1 trial (MNKD)?

No sputum culture conversions were observed among the first 46 participants in the double-blind treatment phase.

Will MannKind (MNKD) share a replay of the ICoN-1 conference call?

Yes; a replay will be available on MannKind’s website within 24 hours and accessible for approximately 90 days.