NDA for NTM Lung Disease Treatment Submitted to FDA

This morning, Insmed Incorporated announced that it has submitted its New Drug Application (NDA) for amikacin liposome inhalation suspension (ALIS) to the U.S. Food and Drug Administration (FDA).

The drug is intended for adult patients with nontuberculous mycobacterial (NTM) lung disease caused by chronic M. abscessus or Mycobacterium avium complex (MAC) infection.

ALIS is an inhaled, once-daily formulation of amikacin, which is an established drug that has exhibited activity against a variety of NTM. Its use, however, is limited by the need to administer it intravenously.

The submission is supported by the company’s pivotal Phase 3 CONVERT (INS-212) study conducted in subjects with refractory NTM lung disease, the completed Phase 2 study TR02-112, and an expanded safety database.

The drug has serious potential, as observed by the reported efficacy and safety in the Phase 2 study. It included 90 participants split into 2 arms. Patients enrolled in the experimental arm were administered 590 mg of liposomal amikacin for inhalation via the PARI Investigational eFlow Nebulizer. Administration time endured for approximately 23 minutes, and the duration continued for 84 days in the double-blind, randomized portion of the study. Participants continued in the open label extension for another 84 days.²

The placebo comparator was administered via a sterile aqueous lipid dispersion for inhalation in the same manner (volume and administration procedures and time) as the experimental arm (nebulization). Participants, however, only continued the placebo administration for 84 days only during the double-blind, randomized portion of the study.²

“We are very excited to announce the completion of this important milestone which begins the formal process of review by the FDA of our application for approval of ALIS to treat patients living with NTM caused by MAC. There are currently no approved therapies in the U.S. to treat this disease,” remarked Will Lewis, President and Chief Executive Officer of Insmed in a press release. “We look forward to continuing our conversations with the FDA during this process.”

The CONVERT study is a randomized, open-label, global Phase 3 trial being conducted in 18 countries at more than 125 sites to confirm the culture conversion results seen in Insmed’s Phase 2 clinical trial of ALIS in patients with refractory NTM lung disease caused by MAC. The proportion of patients who achieve sputum culture conversion (defined as 3 consecutive negative monthly sputum cultures) by Month 6 in the ALIS plus GBT arm compared to the GBT-only arm serves as the primary efficacy endpoint in the study.

Patients who achieve culture conversion by Month 6 will continue in the CONVERT study for an additional 12 months of treatment following the first monthly negative sputum culture. Patients who do not culture convert will have the ability to enroll in the company’s INS-312 open-label extension study.

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References:

1. “Insmed Submits New Drug Application to FDA for ALIS in NTM Lung Disease Caused by MAC.” GlobeNewswire. 29, Mar. 2018.
2. “A Randomized, Double-Blind, Placebo-Controlled Study of Liposomal Amikacin for Inhalation (Arikayce®) in Patients With Recalcitrant Nontuberculous Mycobacterial Lung Disease.” 3, Oct. 2016.