Altimmune has begun a phase 1 clinical trial of its long-acting nonalcoholic steatohepatitis (NASH) drug ALT-801. The asset, like AstraZeneca’s more advanced cotadutide, is a GLP-1/glucagon receptor dual agonist, but it has a less-frequent dosing schedule and potentially superior tolerability.
Maryland-based Altimmune acquired rights to ALT-801 through its 2019 takeover of Spitfire Pharma. The molecule has a glucagon specificity to aid weight loss and a GLP-1 specificity to restore metabolic function, potentially enabling it to improve NASH parameters and suppress stellate cell fibrosis. What sets Altimmune apart from similar assets, though, is the proprietary EuPort domain.
The addition of the domain is intended to facilitate weekly dosing and improved pharmacokinetics. The domain could achieve those objectives by slowing the entry of the drug into circulation.
To Altimmune, slowing the entry of the drug into circulation is about more than just sparing patients from the need to take daily subcutaneous injections. Altimmune is also looking to the formulation to improve the gastrointestinal tolerability of GLP-1/glucagon receptor dual agonists.
Forty percent of obese patients with Type 2 diabetes and nonalcoholic fatty liver disease who took the high daily dose of AstraZeneca’s cotadutide in a phase 2b reported nausea and vomiting early in the study.
Researchers have speculated a less-frequent dosing schedule could improve tolerability. Boehringer Ingelheim dropped a once-daily GLP-1/glucagon receptor dual agonist it was developing with Zealand Pharma and switched its attention to earlier-stage once-weekly assets in 2014. BI 456906 emerged as the preferred candidate, moving into the clinic in 2017 and entering phase 2 in Type 2 diabetes last year. The phase 2 is assessing six doses. Zealand sees potential for once-weekly administration.
Altimmune is giving chase. The phase 1 that recently got underway is now enrolling around 50 healthy overweight or obese volunteers in Australia for the single ascending dose portion of the trial. Altimmune plans to start enrolling around 60 people in the multiple ascending dose part of the trial next year. Readouts are scheduled for next year as well.
The study is intended to set Altimmune up to run a 12-week, 100-subject phase 1b in the U.S. Across the early-phase program, Altimmune will assess safety, tolerability and pharmacokinetics, important endpoints given its pitch for the long-acting ALT-801. Altimmune will also gather data on weight loss and liver fat, particularly in the phase 1b.