Boehringer Ingelheim and pharmaceutical company Pharmaxis announce that Boehringer Ingelheim has initiated a European and North American phase IIa trial in NASH with BI 1467335 (formerly known as PXS-4728A), acquired from Pharmaxis in May 2015. The compound is an oral inhibitor of amine oxidase, copper containing 3 (AOC3), and works by blocking leucocyte adhesion and tissue infiltration in inflammatory processes underlying NASH.
Non-alcoholic fatty liver disease (NAFLD), the most common liver disorder in Western industrialized nations, and its more serious form NASH, is highly prevalent amongst patients with type 2 Diabetes. NASH is a major cause of liver fibrosis and cirrhosis and is an area of high unmet medical need with no treatments currently available. The high prevalence of type 2 diabetes and obesity is expected to make NASH one of the most common causes of advanced liver disorders in coming decades. 25% of the general adult population in the world has NAFLD and the prevalence of NASH has been found to range from 1.5% to 6.45% in current research, a number twice as high as 20 years ago.
In 2016 Boehringer Ingelheim obtained Fast Track Designation from the FDA for the development of BI 1467335 in NASH. Fast track is a process designed to facilitate the development and expedite the review of drugs to treat serious conditions which fill an unmet medical need. The designation provides opportunities for Boehringer Ingelheim to accelerate the development of this investigational drug candidate in NASH.
This phase IIa trial is a multicenter, double-blind design in 150 patients with clinical evidence of NASH. The primary objectives are to establish proof of clinical principle, investigate suitable dosing, and to evaluate the safety of BI 1467335. Patients will be randomized to either one of four dosages of BI 1467335 or to placebo for a 12-week treatment period. A subsequent phase IIb study will seek to confirm and extend these findings.
Dr. Christopher Corsico, Chief Medical Officer Boehringer Ingelheim Boehringer Ingelheim commented, "Advancing BI 1467335 into phase II clinical research is important news for patients with NASH. Boehringer Ingelheim is committed to developing novel therapeutics designed to address unmet medical need and improve public health. Boehringer Ingelheim looks forward to further studying this novel compound in NASH patients".
Boehringer Ingelheim has a long history of excellence in the discovery and development of medicines for cardiometabolic disease patients. It has established a broad portfolio of marketed products for thromboembolic diseases, type 2 diabetes, acute myocardial infarction, hypertension and cardio-renal risk reduction. The cardiometabolic diseases pipeline extends beyond type 2 diabetes and anticoagulation with a focus on innovative drugs for the treatment of the devastating consequences of diabetes.
Pharmaxis CEO Mr. Gary Phillips said, "Pharmaxis selected Boehringer Ingelheim as our partner for PXS-4728A both because of the company's reputation as a leader in cardio metabolic research and development, and its outstanding track record in advancing external research. Today's announcement of the start of this phase IIa clinical trial for NASH is excellent news and is very significant for Pharmaxis. It triggers the payment of an 18 million (A$27m) milestone to Pharmaxis and opens the path to a total of 195 million in milestone payments as the drug progresses through development and approval for this indication. The initiation of phase II trials in a second indication later this year by Boehringer Ingelheim can bring the total potential value of the partnership with Boehringer Ingelheim to 418.5m (A$627m) plus sales milestones and high single digit earnout payments on annual net sales."