FDA Lifts Clinical Hold on Spero’s NTM Therapy

The U.S. Food and Drug Administration has lifted the clinical hold on Spero Therapeutics phase 2 trial of SPR720, an experimental drug in development for nontuberculous mycobacterial infectious lung disease.

Photo: Ankit Mahadevia, CEO of Spero

Nontuberculous mycobacterium (NTM) pulmonary disease is a growing global health concern and major unmet medical need due to a lack of new medications being developed to combat these bacteria. NTM are ubiquitous environmental pathogens that can cause progressive lung damage and respiratory failure, particularly in patients with compromised immune systems or underlying pulmonary disorders. Although rare, the incidence of NTM pulmonary disease is increasing worldwide. It is estimated that approximately 130,000 patients suffer from NTM in the United States and Europe, a figure that is growing at a rate of 8 percent annually. The elderly and people with compromised immune or lung function are at greatest risk, as are patients with bronchiectasis for whom it is estimated that up to 50 percent may also have active NTM pulmonary disease.

SPR720 represents a novel class of antibacterial agents that target enzymes essential for bacterial DNA replication. It is currently under development as an oral therapy for the treatment of non-tuberculous mycobacterial (NTM) disease, a rare orphan disease.

Treatment of pulmonary NTM disease requires prolonged therapy (continuing for approximately 12 to 24 months) with a combination of mostly unapproved drugs and is frequently complicated by tolerability and/or toxicity issues. Additionally, there are currently no oral antibiotics specifically approved for use to treat pulmonary NTM disease.

“Current treatments for nontuberculous mycobacteria are often ineffective and involve lengthy and complex combination regimens that include injectable and/or inhalable antibiotics,” said David Melnick, chief medical officer of Spero. “Through SPR720’s clinical development and potential future marketing approval, we aim to provide appropriate NTM-PD patients with a once-daily oral therapy, in conjunction with existing therapeutic regimens. This has the potential to address a pressing unmet need for an indication that represents a global health concern with increasing incidence.”

The SPR720 program was placed on a clinical hold by the FDA following a review of data from a non-human primate (NHP) toxicology study in which mortalities with inconclusive causality to treatment were observed. The FDA’s decision to lift the hold follows Spero’s submission of a comprehensive study report with detailed analyses from the NHP toxicology study.

Spero plans on engaging with the FDA in the first quarter of 2022 to discuss the re-initiation of the SPR720 phase 2 trial for NTM-pulmonary disease (NTM-PD) patients, with an expected study start date commencing in the second half of 2022.

“Extensive analyses, together with prior clinical and non-clinical data, support our belief that SPR720 has the potential to offer a new, well-tolerated, oral treatment option for patients suffering from NTM-PD,” said Ankit Mahadevia, CEO of Spero.

Author: Rare Daily Staff