Bristol-Myers Squibb and AstraZeneca reported positive results from a phase III, pivotal trial of saxagliptin (Onglyza) for the treatment of type 2 diabetes. Saxagliptin could rival Merck’s newest diabetes drug, Januvia. The global diabetes treatment market is $23 billion, according to data from IMS Health.
AstraZeneca reportedly paid BMS $100 million upfront and up to $950 million more in milestones in a partnership develop two investigational drugs for the diabetes. AstraZeneca agreed to take on 75% of the development costs of both compounds, including saxagliptin –- a dipeptidyl peptidase-4 (DPP-4) inhibitor completing phase III – and dapagliflozin (BMS-512148), a sodium-glucose cotransporter-2 (SGLT2) inhibitor in phase IIb.
The companies stated they will share global sales and revenue on both products. In December 2006, BMS granted Otsuka Pharmaceutical exclusive rights in Japan to develop and commercialize saxagliptin for type 2 diabetes.*
Saxagliptin is being developed to improve the timing of insulin release thus decreasing high blood sugar.
The trial was set up as a multicenter, randomized, double-blind, placebo-controlled, parallel-group study enrolled 401 treatment-naïve subjects.
Subjects were randomized to one of four separate treatment arms: saxagliptin 2.5 mg, 5 mg or 10 mg or placebo, once daily. The primary endpoint was the change from baseline to Week 24 in glycosylated hemoglobin level (A1C).
The secondary endpoints of the study included achievement of A1C of less than 7% and changes from baseline in fasting plasma glucose (FPG). Saxagliptin 2.5 mg, 5 mg and 10 mg demonstrated a significant mean change in A1C from baseline of -0.4%, -0.5% and -0.5%, respectively, resulting in a placebo-adjusted change of -0.6%, -0.6% and -0.7%, respectively (p-value less than 0.0001).
Reductions in A1C levels were seen as early as four weeks after initiation of saxagliptin treatment, the first scheduled A1C measurement point.A1C of less than 7% at Week 24 was observed in 35%, 38% and 41% of subjects in the saxagliptin 2.5 mg, 5 mg and 10 mg arms, respectively, compared with 24% of individuals treated with placebo (p-value not significant at the 2.5 mg dose; p-value at the other doses less than 0.05).
Treatment was well tolerated; over 24 weeks saxagliptin had an adverse event profile similar to placebo. The drug was not associated with weight gain in any of the treatment groups.
Based on the results, BMS and AstraZeneca plan to submit a new drug application (NDA) in the U.S. in mid 2008.
* Updated: CTToday previously reported that Takeda Pharmaceutical owned the Japanese rights to saxagliptin, in fact it does not. As stated above, Otsuka Pharmaceutical owns those rights.