MannKind Corporation, a leader in the development and commercialization of inhaled therapeutic products to treat endocrine and orphan lung diseases, today announced the launch of an adaptive Phase 2/3 study for its clofazimine inhalation suspension (MNKD 101). Moreover, a recently published paper in the American Society for Microbiology journal Antimicrobial Agents and Chemotherapy has explored the potential of clofazimine inhalation suspension to treat nontuberculous mycobacterial (NTM) infection, sidestepping the systemic toxicity associated with oral treatments.
Pulmonary NTM infection is an increasingly concerning global health issue, with estimates suggesting up to 180,000 people in the United States are living with this serious infection. Women, the elderly, and those with underlying lung conditions are particularly vulnerable to the symptoms of NTM lung disease such as reduced lung function, cough, fatigue and impaired quality of life. To combat this growing problem, the FDA has granted MNKD-101 both orphan lung and QIDP designation for the treatment of pulmonary NTM infections— a major step forward in the fight against this devastating affliction.
NTM lung disease presents a unique challenge to patients, as it often requires prolonged oral drug treatments that can result in high systemic toxicity and serious side effects. But Michael Castagna, PharmD, Chief Executive Officer of MannKind Corporation, is hopeful that inhaled clofazimine may provide a much-needed solution. The preclinical and Phase 1 data looks promising, offering patients the potential for improved NTM therapy.
The 28-day preclinical toxicology study included toxicokinetic analyses on days 29, 56, and 84 to uncover a comprehensive understanding of the toxicity of the substance. By analyzing the results, researchers were able to gain a deeper insight into the potential adverse effects of the substance.
After administering the drug at three different dose levels, researchers were surprised to find a significant amount of residual drug still present in the lung tissue, resulting in a prolonged residence time in the lungs.
At 28 and 56 days post-dosing, drug concentrations in the lung remained significantly above the average minimum inhibitory concentration (MIC) of Mycobacterium avium complex (MAC) and Mycobacterium abscessus (Mabsc), resulting in measurable levels of clofazimine.
MannKind Corporation’s Chief Scientific Officer, Thomas Hofmann, MD, PhD, is thrilled with the preclinical results of their inhaled clofazimine drug. After dosing for 28 days followed by a 56-day drug holiday, the drug concentration in the lung remained well above the average NTM MIC. The Phase 1 study also showed that the investigational formulation was very well tolerated and had great lung loading capability. MannKind is now eager to study the efficacy and safety of the drug in an NTM patient population.
MKC-CI-001, a Phase I randomized, double-blind, placebo-controlled trial, was conducted to assess the safety, tolerability, and pharmacokinetics of MNKD-101. This study included both single- and multiple-ascending doses of clofazimine administered via a jet nebulizer, at three dose levels. After rigorous evaluation, the key safety findings of the trial revealed that MNKD-101 was generally safe and well-tolerated.
Patients have reported a generally good tolerance to Clofazimine inhalation solution when taking daily doses of up to 90 mg, making it an effective and safe medication to use.
No significant issues were found during lab analysis, nor were there any reports of QT prolongation or serious side effects. Everything appears to be in order!
MannKind Corporation (Nasdaq: MNKD) is dedicated to transforming the lives of those living with endocrine and orphan lung diseases by creating and delivering innovative therapeutic products and devices. Our goal is to provide solutions to unmet medical needs and make a positive difference in people’s lives.
We are driven to use our expertise in formulation and device engineering to reduce the impact of diseases like diabetes, pulmonary arterial hypertension (PAH) and nontuberculous mycobacterial (NTM) lung disease. With our advanced dry-powder formulations and inhalation devices, patients now have the option of a fast and convenient way to deliver medicines directly to their lungs, which can have a localized effect or enter the systemic circulation.
At Mannitarians, we are driven by a shared passion to empower people with the freedom to live life on their own terms. Our nationwide team of dedicated professionals is on a mission to give individuals control of their health and well-being. Together, we are making a difference and creating a brighter future for everyone.