Big Pharmas collaborate on diabetes

Pharmaceutical companies AstraZeneca and Bristol-Myers Squibb have announced a collaboration to develop and commercialise two investigational compounds for the treatment of type 2 diabetes.

Saxagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, is currently in phase III development. Upon successful completion of the development program, the companies plan to file for US regulatory approval of saxagliptin during the first half of 2008.

DPP-4 inhibitors are a new class of diabetes drugs that work by increasing and prolonging the action of hormones called incretins. Incretins decrease blood sugar by increasing consumption of sugar by the body, mainly through increasing insulin production in the pancreas, and by reducing production of sugar by the liver.

By enhancing the effect of active incretin hormones in the body, DPP-4 inhibitors improve timely insulin release and ultimately decrease high blood sugar levels in patients with type 2 diabetes.

Dapagliflozin (previously referred to as BMS-512148), a sodium-glucose cotransporter-2 (SGLT2) inhibitor, is currently in phase IIb development. The SGLT2 transporter protein is located only in the kidney, where it normally reabsorbs glucose from urine while waste products are filtered out.

Patients with type 2 diabetes continue to reabsorb glucose from the urine, even though this process contributes to hyperglycemia. Dapagliflozin has a novel mechanism of action that blocks re-absorption of glucose from urine. Inhibiting SGLT2 activity decreases re-absorption of glucose by the kidney, helping to improve glucose control in patients with type 2 diabetes.

The collaboration on these compounds is worldwide. Should either party develop additional DPP-4 or SGLT2 compounds, the other company can elect to add those compounds to the collaboration.

Terms of the agreements include an upfront payment of US$100 million by AstraZeneca to Bristol-Myers Squibb. The companies have agreed upon initial development plans for the two compounds.

Bristol-Myers Squibb may also receive additional payments of up to $650 million based on development and regulatory milestones for the two compounds. In addition, potential sales milestones up to $300 million per product are also possible.

The companies will jointly develop the clinical and marketing strategy of the compounds, and post-launch will share commercialisation expenses and profits/losses equally on a global basis.

Source: AstraZeneca