FDA has approved Boehringer Ingelheim and Eli Lilly’s linagliptin tablets for the treatment of type 2 diabetes alongside diet and exercise measures. Approval covers use of the once-daily dipeptidyl peptidase-4 inhibitor either as monotherapy or in combination with other type 2 diabetes drugs including metformin, sulphonylurea, and pioglitazone, for reducing HbA1c levels.
Clearance in the U.S. was based on data from a clinical trial program including some 4,000 adults with type 2 diabetes. Three placebo-controlled studies evaluated linagliptin either as monotherapy or in combination with oral metformin and sulphonylurea in patients whose blood sugar was not adequately controlled on either of the latter two drugs. The studies confirmed linagliptin significantly reduced HbA1c levels when used as monotherapy and when added to the existing diabetes treatments. A fourth study confirmed that adding linagliptin to pioglitazone therapy reduced HbA1c levels to a greater extent than pioglitazone monotherapy.
The clinical program also confirmed that linagliptin reduced fasting plasma glucose levels and did not cause additional increases in body weight when used either as monotherapy or in combination with metformin, sulphonylurea, and/or pioglitazone.
Boehringer Ingelheim and Lilly point out approval of linagliptin in the U.S. represents the first regulatory milestone since they established their diabetes alliance at the start of 2011. “Our alliance with Boehringer Ingelheim represents one of the most robust diabetes pipelines in the pharmaceutical industry,” comments Enrique Conterno, Lilly Diabetes president. “Linagliptin is the first regulatory approval of what we hope will be many new treatment options this alliance brings to the millions of people living with type 2 diabetes.”
The firms’ diabetes alliance is focused on developing and commercializing a portfolio of diabetes compounds currently in mid- and late-stage development. These include Boehringer Ingelheim’s two oral diabetes agents linagliptin and BI10773 as well as Lilly’s two basal insulin analogues, LY2605541 and LY2963016. The deal also includes an option to co-develop and co-commercialize Lilly’s Phase II-stage anti-TGF-beta monoclonal antibody.
Under the terms of the agreement Boehringer Ingelheim received a €300 million (about $443.9 million) up-front payment from its partner and could earn up to another €625 million (about $924.8 million) in success-based regulatory milestones for linagliptin and BI10773. Lilly will be eligible to receive up to a total of $650 million in success-based regulatory milestones on its two basal insulin analogues. If Boehringer Ingelheim decides to opt-in to Phase III development and potential commercialization of the anti-TGF-beta monoclonal antibody, Lilly would be eligible for up to $525 million in opt-in and success-based regulatory milestone payments.
Boehringer Ingelheim’s BI10773 is a sodium-dependent glucose co-transporter-2 (SGLT-2) inhibitor, which started in Phase III clinical trials in 2010. Lilly’s two basal insulin analogue candidates are expected to enter Phase III clinical testing in 2011. LY2605541 is a structurally novel basal insulin analogue, and LY2963016 is a new insulin glargine product.