Having successfully launched one new diabetes drug into the market with the approval of Onglyza (saxagliptin) in August, Bristol-Myers Squibb and its partner AstraZeneca are hoping this month to move another innovative diabetes project closer to market.
Phase III data from the group’s sodium glucose co-transporter2 (SGLT2) inhibitor, dapaglifozin, is due to be presented at the European Association for the Study of Diabetes on September 29 and will be eagerly watched given that these will be the first late stage results from a drug of this class. Many will also be looking for positive data to provide validation of this new approach to tackling diabetes.
Novel mode of action
Dapaglifozin works by inhibiting the protein SGLT2, which is responsible for re-absorbing glucose from the body and therefore regulating blood sugar levels. Inhibiting SGLT2 limits the amount of glucose that is re-absorbed by the kidneys, which is then excreted in the urine, preventing hyperglycaemia. This new class of anti-diabetic agent is currently attracting increasing levels of interest and expectation (Therapeutic Focus – Growing interest in SGLTs as novel diabetic agents, June 15, 2009).
The data presented at the conference will be from Study 14, a 24 week trial in 571 patients with type II diabetes, assessing three doses of the drug versus placebo and as an additional therapy to standard diabetes drug metformin.
If the trends seen in the phase IIb trials are repeated in this study then the drug does stand a good chance of gaining approval especially given its impressive weight loss profile. As well as the product's efficacy, people will also be keenly watching the drug’s safety, especially given the FDA’s tougher stance on diabetes drugs.
In the phase IIb trial the most commonly reported side effects were urinary tract infections, headaches and nausea, something that should not give the regulator too much cause for concern.
Positive data from this and other phase III studies that are being conducted could see the drug filed in the second half of 2010 with marketing approval possible by the early part of 2011. Consensus sales forecasts for the drug currently stand at $361m for 2014.
Further dapaglifozin data is expected later on in the year as the group reports Study 13, which sees the drug used either as a first line monotherapy or in combination with metformin.
Knock on effect
While dapaglifozin may be the most advanced SGLT2 inhibitor (see table below), the growing interest in the field was seen yesterday with the dramatic share price hike experienced by Lexicon Pharmaceuticals, up 51% after it reported positive phase I safety data for LX4211 and moved the drug into phase II trials.
If the data from dapaglifozin is positive the news could send shares in Lexicon up again as it would provide investors with more reassurance about the class. LX4211, which is expected to generate phase II data by the first quarter of 2010, also represents the only unpartnered mid-stage asset in development and positive data from dapaglifozin are sure to speed up and increase interest in licensing talks.
|Pipeline for SGLT inhibitors||WW annual sales ($m)|
|Phase III||SGLT2 inhibitor||Dapagliflozin||Bristol-Myers Squibb||Bristol-Myers Squibb + AstraZeneca||Dec - 2011||4||78||223||361|
|SGLT2 inhibitor & biguanide||Dapagliflozin & Metformin||Bristol-Myers Squibb/Lipha||Bristol-Myers Squibb + AstraZeneca||Dec - 2012||-||-||-||-|
|Phase II||SGLT2 inhibitor||Remoglifozin (KGT-1681)||Kissei Pharmaceutical||Kissei Pharmaceutical||Jun - 2012||-|
|Canagliflozin (TA-7284)||Tanabe Seiyaku||Mitsubishi Tanabe Pharma + Johnson & Johnson||Mar - 2016||-||-||-||-|
|BI 44847||Ajinomoto||Boehringer Ingelheim||-||-||-||-||-|
|BI 10773||Boehringer Ingelheim||Boehringer Ingelheim||-||-||-||-||-|
|LX4211||Lexicon Pharmaceuticals||Lexicon Pharmaceuticals||-||-||-||-||-|
|Phase I||SGLT2 inhibitor||CSG452||Chugai||Chugai||-||-||-||-||-|
|TS-033 (backup compound)||Taisho Pharmaceutical||Taisho Pharmaceutical||-||-||-||-||-|
|SGLT1 inhibitor||KGA-2727||Kissei Pharmaceutical||GlaxoSmithKline + Kissei Pharmaceutical||-||-||-||-||-|
|SGLT1/SGLT2 inhibitor||SAR 7226||Sanofi-Aventis||Sanofi-Aventis||-||-||-||-||-|
|SGLT2 antisense||ISIS-SGLT2Rx||Isis Pharmaceuticals||Isis Pharmaceuticals||-||-||-||-||-|
|Pre-clinical||SGLT2 inhibitor||LX4212||Lexicon Pharmaceuticals||Lexicon Pharmaceuticals||-||-||-||-||-|
|SGLT2 antisense||ISIS 388626||Isis Pharmaceuticals||Isis Pharmaceuticals||-||-||-||-||-|