New class of diabetes drugs going strong

Bristol-Myers Squibb (BMS) presented initial Phase II results for its sodium glucose cotransporter-2 (SGLT2) inhibitor at this week's Annual Conference of the American Diabetes Association.

The New York-based company is developing the drug, called dapagliflozin, together with AstraZeneca.

BMS and AstraZeneca are not alone in the quest though; Britain's pharma giant GlaxoSmithKline (GSK) has a similar drug (sergliflozin) in Phase II studies and French company Sanofi-Aventis is testing another molecule (AVE2268) in Phase IIb trials; the results are expected in the fourth quarter of 2007.

Whichever of these drugs makes it to the market first, will have the first crack at a global diabetes drug market that was valued at $15bn (€11.2bn) in 2005.

This is expected to grow dramatically over the next five years to over $22bn in 2012, as the addressable patient population continues to increase and new, oral, injectable and pulmonary premium priced products enter the market to address high unmet clinical needs.

The SGLT2 protein target is only found in the kidney, and its job is to take glucose out of urine and put it back into the bloodstream.

"The idea is to lower blood-sugar levels in a different way," said Dr. Bernard Komoroski, senior research investigator for BMS.

Researchers hope that if the SGLT2 function is blocked, more glucose will be excreted in the urine, therefore helping diabetes patients maintain the right blood glucose level.

Diabetes is characterised by a lack of the hormone insulin or insulin resistance which if untreated leads to high levels of glucose in blood.

Dapagliflozin has been tested in a 47-patient trial and it was found to help improve fasting glucose values over 14 days.

Patients received one of three different doses alone or with the oral generic medication metformin.

The most common side effects of the drug were constipation, nausea and diarrhoea in some of the patients, and there were two reports of hypoglycaemia, and two patients developed vaginal infections.

As SGLT2 inhibitors do not intervene with glucose metabolism, they could be complementary to mainstream approaches to glucose regulation.

The current therapies in the market are based on one of the following mechanisms: peroxisome proliferatoractivated receptor-gamma (PPAR-gamma) activators, such as Takeda's Actos (pioglitazone) and GSK's Avandia (rosiglitazone);

DPP-4 antagonists such as Januvia (sitagliptin), which is manufactured by Merck & Co; and GLP-1 analogues, where Eli Lilly' Byetta (exenatide) is the flagship.

There are nearly 250 million people worldwide who suffer from diabetes, according to the International Diabetes Federation (IDF).

Oral anti-diabetics are a leading category of drugs - $8.19 billion - and showed a growth rate of 6.3 per cent from the total global sales in 2004.

GSK's Avandia is the leader in this market.

Since the drug's approval, about 60 million prescriptions have been issued.

Avandia generated $3.3bn in sales last year and is Glaxo's second-best-selling drug.

Takeda Pharmaceuticals' Actos (pioglitazone) is the next biggest-selling oral anti-diabetic with sales of $2.77bn.

This accounted for a quarter of Takeda's revenue last fiscal year and was the company's best seller.

The deal that BMS and AstraZeneca reached last January and which could bring BMS up to $1.35bn, also includes another experimental drug called saxagliptin which recently completed Phase III trials.

This drug is a DDP-4 inhibitor and if eventually gets approved by the US Food and Drug Administration (FDA), it would compete in the market with Merck's & Co's Januvia.

Some analysts give this drug only a 20 per cent chance of winning approval, although they estimate that if the drug does get approved it could launch in 2012 and have peak sales of $750m. AstraZeneca is not the only company expanding its interest in diabetes research.

Pfizer recently bought out BioRexis, a company which is developing GLP-1 based drugs.