Bristol-Myers Squibb has impressed observers at the American Diabetes Association meeting in Chicago with its first Phase II data on dapagliflozin, the first of a new family of drugs designed to treat the disease.
B-MS and joint development partner AstraZeneca presented findings on a 14-day, Phase IIa study of dapagliflozin, a selective inhibitor of the sodium-glucose transporter 2, which showed that the experimental drug could control blood-sugar levels in diabetics and appears to be safe. The data were from a double-blind, placebo-controlled, randomised, parallel-group study of 47 subjects who were either drug-naive or on a stable dose of metformin and they were randomised to receive either placebo or a 5mg, 25mg or 100mg dose of dapagliflozin in addition to their stable metformin dose and/or diet alone.
The primary endpoint of the study of assessing both the safety and tolerability profiles of multiple doses of dapagliflozin were meet and B-MS noted that there were no discontinuations due to adverse events and indeed no serious adverse events were reported. Furthermore, the firm noted that the compound caused a statistically significant drop in fasting serum glucose, a measurement of blood sugar after a person has not eaten for eight to 12 hours.
Dapagliflozin is the most advanced compound in the SGLT2-inhibitor class which is exciting researchers because of its novel way of controlling blood sugar levels by discouraging the kidneys from reabsorbing the glucose contained in urine. It is still early days for the compound but analysts have suggested that GLT2-inhibitors could become first-line therapy for type 2 diabetes patients who are poorly controlled on diet or exercise. B-MS and AstraZeneca are hoping to get dapaglifozin approved by 2010.
Strong showing for saxagliptin too
Also of interest was B-MS’ presentation at the ADA of Phase III data on the dipeptidyl peptidase-4 inhibitor saxagliptin, which is also partnered with AstraZeneca, which showed that the compound combined with metformin significantly reduced haemoglobin A1C levels, compared to metformin alone.
In the study, 743 patients with type 2 diabetes who were already being treated with metformin were randomised to receive one of three dosages of saxagliptin, or placebo. After 24 weeks, patients who received the B-MS/AstraZeneca drug experienced decreases in haemoglobin A1C levels of between 0.73% and 0.83%, compared to baseline. Between 37% and 44% of those receiving saxagliptin reached their target A1C levels, compared to 17% of those who received only metformin.
The companies plan to seek approval from the US Drug Administration for saxagliptin in the first half of 2008 but it will have much ground to make up on Merck & Co’s Januvia (sitagliptin) and (probably) Novartis' Galvus (vildagliptin). PharmaTimes World News will look at the numerous ADA presentations on these compounds tomorrow and the battle to be the leading DPP-4 inhibitor, as well as the heated discussions that are taking place at the conference about the safety of GlaxoSmithKline’s Avandia (rosiglitazone).
