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

Core Viewpoint - MannKind Corporation has announced the discontinuation of its Phase 3 ICoN-1 clinical trial for MNKD-101, a nebulized clofazimine inhalation suspension, due to a lack of efficacy in treating refractory nontuberculous mycobacterial (NTM) lung disease [1][8]. Group 1: Clinical Trial Details - The ICoN-1 trial was a multi-national, randomized, double-blind, placebo-controlled Phase 3 study aimed at evaluating the efficacy and safety of clofazimine inhalation suspension in adults with refractory NTM lung disease caused by mycobacterium avium complex (MAC) [5]. - An analysis of sputum culture conversion data from the first 46 participants showed no conversions, leading to concerns about meeting the study's primary endpoint [2]. - The independent Data Safety Monitoring Board (DSMB) reviewed the data and agreed to discontinue the trial due to futility, although no safety concerns were identified during the study [2][8]. Group 2: Future Developments - Despite the discontinuation of MNKD-101, the company remains optimistic about MNKD-102, a dry powder inhalation (DPI) formulation of clofazimine, which is progressing toward Phase 1 development [3][8]. - The company is committed to understanding the factors that led to the failure of the nebulized formulation and intends to apply these insights to future development efforts [3]. Group 3: NTM Disease Context - NTM lung disease is a rare but significant global health concern, with rising prevalence and associated morbidity, particularly affecting individuals with underlying conditions such as COPD, asthma, and bronchiectasis [6][7]. - The most common type of NTM is MAC, which accounts for approximately 80% of NTM lung disease cases in the U.S., with an estimated prevalence of over 100,000 cases in the U.S. and over 150,000 in Japan as of 2022 [7].