MannKind Gets PMDA Nod for Phase 3 Trial in Japan for NTM Lung Disease Treatment

MannKind Corporation, a company specializing in innovative inhaled therapeutic products for endocrine and orphan lung diseases, has been granted approval by Japan’s Pharmaceuticals and Medical Devices Agency (PMDA) to launch a Phase 3 study of Clofazimine Inhalation Suspension. This clinical trial, named ICoN-1, aims to evaluate the treatment's efficacy and safety for patients suffering from NTM (nontuberculous mycobacteria) lung disease. With this clearance, the study is now authorized to proceed in four countries: the United States, Japan, South Korea, and Australia. Approval from Taiwan is anticipated by the fourth quarter of 2024.

Dr. Kozo Morimoto, the lead principal investigator for ICoN-1 in Japan and Chief Doctor at the Respiratory Disease Center at Fukujuji Hospital, expressed optimism about the study. Morimoto emphasized the need for safe and effective treatments for NTM lung infections, which are becoming increasingly prevalent both in Japan and worldwide.

The ICoN-1 study officially began in the United States in June 2024, with the first patient randomized in September. The study aims to enroll around 230 participants across more than 100 sites globally to ensure at least 180 participants are evaluable for efficacy. Key details about the study are available on ClinicalTrials.gov under the identifier NCT06418711.

The ICoN-1 trial is a multi-national, randomized, double-blind, placebo-controlled Phase 3 study. It evaluates the efficacy and safety of Clofazimine Inhalation Suspension when used alongside guideline-based therapy in adults with refractory NTM lung disease caused by Mycobacterium avium complex (MAC). The trial will be followed by an open-label extension. In the U.S., the co-primary endpoints are sputum culture conversion (from positive to negative for NTM) and changes in quality of life from baseline to the end of the sixth month. Outside the U.S., the primary endpoint is solely sputum culture conversion.

In May 2024, the U.S. Food and Drug Administration (FDA) granted Fast Track designation to Clofazimine Inhalation Suspension for treating NTM lung disease. This designation aims to expedite the review of drugs that treat serious conditions and fill an unmet medical need. The FDA had previously designated this treatment as both an orphan drug and a qualified infectious disease product (QIDP), which could provide the product with up to twelve years of market exclusivity.

Clofazimine Inhalation Suspension has also been granted a patent (No. 11,793,808) in the United States, with the patent not set to expire until June 8, 2039. Additionally, a corresponding patent was granted in Japan, and applications are pending in other major markets.

NTM lung infections are a growing global health concern, associated with high morbidity, shortened lifespan, and significant impacts on patients' quality of life. NTM bacteria are found naturally in the environment, including water and soil, and can cause debilitating symptoms such as chronic cough and fatigue, particularly in individuals with underlying conditions like COPD, asthma, and bronchiectasis. While there are nearly 200 species of NTM, Mycobacterium avium complex (MAC) is the most common, accounting for about 80% of NTM lung disease cases in the United States. This condition is more prevalent among women over the age of 65, with over 100,000 cases reported in the U.S. in 2022 and more than 150,000 in Japan.

MannKind Corporation focuses on developing inhaled therapeutic products to address significant unmet medical needs for those with endocrine and orphan lung diseases. The company's technologies facilitate the rapid and convenient delivery of medications to the deep lungs, offering potential for both local and systemic effects. MannKind remains committed to leveraging its expertise to improve the quality of life for patients living with these challenging conditions.