RedHill Biopharma Ltd., a specialty biopharmaceutical company, today announced that it has initiated its Phase 3 study to evaluate the safety and efficacy of RHB-204 as a potential first-line, stand-alone, oral treatment of pulmonary nontuberculous mycobacteria (NTM) disease caused by  Mycobacterium avium Complex (MAC) – a rare disease for which there is no FDA-approved first-line therapy.

"NTM is a debilitating disease that can cause scarring, fibrosis and the formation of cavities or pits in the lungs, which can lead to potentially fatal respiratory failure. People with existing lung conditions, such as bronchiectasis and those with COPD, are particularly susceptible," said Prof. Kevin Winthrop, MD, MPH, Professor of Infectious Diseases, Oregon Health & Science University, and study Principal Investigator. "NTM is notoriously resistant to most antibiotics and challenging to treat, and there is no FDA-approved first-line therapy for the approximately 110,000 cases of NTM infection in the U.S. This study of orally-administered RHB-204, if successful, represents an opportunity to make a breakthrough in managing NTM infections."

"Treatment of NTM disease requires multiple antibiotics and an extended treatment course due to the risk of development of resistance1," said Aida Bibliowicz, RedHill's Vice President of Clinical Affairs. "Many patients fail these types of therapies and more than half will have either recurring disease or a new infection after completing treatment2, making new treatment options for NTM an urgent need."

The multi-center, randomized, double-blind, two-part, placebo-controlled, parallel-group Phase 3 study will be conducted at up to 40 sites across the U.S. and aims to enroll 125 patients, randomized at a 3:2 ratio to receive either RHB-204 or placebo. The study is designed to evaluate the safety and efficacy of RHB-204 in patients with symptomatic Mycobacterium avium Complex (MAC) lung disease. Study endpoints include sputum culture conversion at month six of treatment with RHB-204, compared to placebo and patient-reported outcomes, including improvements in physical functioning, respiratory symptoms and fatigue. Following this assessment (part one of the study), patients may be eligible to continue double-blinded treatment for up to 16 months (part two). Sustainability of clinical benefit and durability of microbiological response will be assessed at month 16 and again three months after treatment completion.

RHB-204 was recently granted Orphan Drug designation, extending U.S. market exclusivity for RHB-204 by an additional seven years, for a potential total of 12 years upon FDA approval. RHB-204 had also previously been granted a Qualified Infectious Disease Product (QIDP) designation by the FDA, providing eligibility for Fast-Track development, NDA Priority Review and a five-year extension of U.S. market exclusivity, if approved.

The Phase 3 study of RHB-204 is registered on www.ClinicalTrials.gov, a web-based service by the U.S. National Institute of Health, which provides public access to information on publicly and privately supported clinical studies.   

About Pulmonary Nontuberculous Mycobacteria (NTM) Disease

Pulmonary nontuberculous mycobacteria (NTM) disease is a chronic and debilitating lung disease caused by ubiquitous environmental bacteria found in soil, as well as natural and engineered water systems. The most common NTM symptoms include fever, weight loss, chest pain, and blood in sputum3. Pulmonary NTM disease can lead to recurring cases of bronchitis and pneumonia and can, in some cases, lead to respiratory failure4. Although rare, the incidence and prevalence of pulmonary NTM disease are increasing in many areas of the world5. There were an estimated 110,000 pulmonary NTM disease patients in the U.S. in 20176. Pulmonary manifestations account for 80-90% of all NTM-associated diseases7, and approximately 80% of pulmonary NTM disease are caused by Mycobacterium avium Complex (MAC)8.

About RHB-204

RHB-204 is a proprietary, fixed-dose oral capsule containing a combination of clarithromycin, rifabutin, and clofazimine, developed for the treatment of pulmonary NTM disease caused by Mycobacterium avium Complex (MAC). RHB-204 was granted both FDA Orphan Drug designation for the treatment of NTM disease and QIDP Designation under the Generating Antibiotic Incentives Now Act (GAIN Act), extending U.S. market exclusivity for RHB-204 to a potential total of 12 years to be granted at the time of FDA approval. RHB-204 is also covered by U.S. patents which extend patent protection until 2029 and a pending U.S. patent application which, if allowed, could extend RHB-204 patent protection until 2041.      

About RedHill Biopharma

RedHill Biopharma Ltd. (Nasdaq: RDHL) is a specialty biopharmaceutical company primarily focused on gastrointestinal and infectious diseases. RedHill promotes the gastrointestinal drugs, Movantik? for opioid-induced constipation in adults9, Talicia? for the treatment of Helicobacter pylori (H. pylori) infection in adults10, and Aemcolo? for the treatment of travelers' diarrhea in adults11. RedHill's key clinical late-stage development programs include: (i) RHB-204, with an ongoing Phase 3 study for pulmonary nontuberculous mycobacteria (NTM) disease; (ii) opaganib (Yeliva?), a first-in-class SK2 selective inhibitor targeting multiple indications with a Phase 2/3 program for COVID-19 and Phase 2 studies for prostate cancer and cholangiocarcinoma ongoing; (iii) RHB-104, with positive results from a first Phase 3 study for Crohn's disease; (iv) RHB-102 (Bekinda?), with positive results from a Phase 3 study for acute gastroenteritis and gastritis and positive results from a Phase 2 study for IBS-D; (v) RHB-107 (upamostat), a Phase 2-stage serine protease inhibitor with a planned Phase 2/3 study in symptomatic COVID-19 and targeting multiple other cancer and inflammatory gastrointestinal diseases;  and (vi) RHB-106, an encapsulated bowel preparation.