CC - Transition Therapeutics reports topline phase 2 results for Lilly-partnered GLP-1/glucagon dual agonist TT401 (LY2944876) –
Transition Therapeutics announced positive topline results for a phase 2 study of its Lilly-partnered once-weekly GLP-1/glucagon dual agonist TT401 (LY2944876) earlier today. The 24-week trial (n=420) investigated the safety and efficacy of four once-weekly doses of the oxyntomodulin analog (10 mg, 15 mg, 30 mg, and 50 mg) against exenatide (2 mg) once-weekly and placebo once-weekly. Participants treated with TT401 experienced A1c reductions of up to 1.4%” (baseline A1c = 8.2%), similar to the exenatide-treated participants and statistically superior to the placebo-treated participants. More notably, the study demonstrated dose-dependent weight loss with TT401 (up to 3.3 kg; 7.3 lbs) with statistically significant weight reductions with the highest dose of TT401 (50 mg) compared to both placebo and exenatide. TT401 was safe and well-tolerated, with a similar number of study discontinuations and serious adverse events in both the TT401 and exenatide arms. As expected, the most frequent adverse events were gastrointestinal in nature. Transition Therapeutics noted that it is now up to Lilly to decide if the company will move forward with development of the candidate; a decision which would trigger a milestone payment to Transition Therapeutics. TT401 is the most advanced GLP-1/glucagon dual agonist in the competitive landscape and is the first to report phase 2 results. These topline data appear to confirm the suggestion from preclinical and phase 1 data that the dual agonists’ main advantage over existing GLP-1 agonists is improved weight loss, a promising result. Several other companies are investing in GLP-1/glucagon dual agonist candidates as well, including Sanofi (phase 1), Janssen/Hanmi (phase 1), AZ (phase 1), Xenetic Biosciences (phase 1), Zealand (preclinical), Zealand/BI (preclinical), and OPKO Health (preclinical). Novo Nordisk has indicated that it eventually intends to co-formulate its phase 1 glucagon analog with liraglutide as well. We would expect Lilly to move ahead for a variety of reasons, particularly given that it is the most advance (only candidate in phase 2).
-- by Helen Gao, Sarah Odeh, and Kelly Close