Given the growing incidence of diabetes and the search for novel compounds to help fight this increasing epidemic it was almost inevitable that someone would step in and license the last remaining glucokinase activator (GKA) still in the hands of a small company.
Yesterday, private US company TransTech Pharma succumbed to the charms of a larger pharma partner and announced that Forest Laboratories had agreed a deal worth up to $1.1bn for its phase II ready GKA TTP-399 and other phase I and pre-clinical GKAs. While the bio-dollar amount is largely irrelevant what is impressive is the $50m upfront fee TransTech secured for what are such relatively early stage candidates, indicating burgeoning interest in the field.
The deal mirrors a similar one struck between Amgen and Array BioPharma late last year that saw Array pick up $50m upfront for ARRY-403, a phase I GKA. At the time EP Vantage predicted that it could spark interest in TransTech’s unpartnered GKA assets, a forecast that has come to pass only six months later (Array bounces back on novel diabetes hope, December 16, 2009).
The reason why pharma companies appear to be so interested in GKA’s is their novel mechanism of action. Glucokinase is an enzyme that is found in both the liver and the pancreas. In the pancreas glucokinase regulates insulin secretion and in the liver it controls glucose consumption when levels become high.
It is this control of glucose consumption by the liver, which appears to be reduced in type II diabetes, that GKAs target. Also, by controlling the consumption of glucose in the liver and not in the pancreas where glucose is released, GKAs are thought to reduce the risk of hypoglycemia, or low blood sugar, one of the most difficult to control side effects of many diabetes treatments. GKAs are also thought to reduce fasting blood glucose levels, another benefit that makes them attractive as diabetes treatments.
However, despite their seeming promise the products are still very new and of the seven currently in clinical development none have made it into pivotal phase III trials.
|Clinical pipeline of glucokinase activators|
|Phase II||TTP399||TransTech Pharma||Novo Nordisk|
|Phase I||AMG 151 / ARRY-403||Amgen||Array BioPharma|
|LY2599506||Eli Lilly||OSI Pharmaceuticals|
AstraZeneca currently leads the field in sheer volume of products with its two phase II compounds, AZD6370 and AZD1656, and phase I drug AXD6714. AZD6370 has recently completed a phase I trial and AZD1656 is currently in a number of phase I and II trials including one evaluating its efficacy as an add-on treatment to metformin, which is due to complete in October of this year.
This study will be closely watched as it and the others that Astra are conducting could be valuable predictors as to how the class performs as a whole and also their potential to combine with other diabetes treatments, where some see a large market for the drugs.
There are currently four other listed trials for AZD1656 on clinicaltrials.gov indicating that this is the product that Astra is throwing most of it resources at in the GKA space.
Being phase II ready TTP399 is the next most advanced pill, and while it is now in the hands of a bigger player following the Forest deal, it is interesting to note that the drug and another one that has since been abandoned by TransTech, TTP355, were originally licensed from Novo Nordisk as part of a pre-clinical stage deal in February 2007 for undisclosed terms.
Conversely Eli Lilly picked up LY2599506 (PSN010) from Prosidion, a subsidiary OSI Pharmaceuticals, in January 2007 for $25m upfront and a further $360m in potential milestones.
The other GKA products in development are still at too early a stage for their originating companies to say too much about, but there is one newcomer to the space, Takeda’s TAK-329, which the company unveiled late last year.
However, despite their relative youth, the fact that big pharma in the form of Eli Lilly, Amgen, Takeda, Astra and now Forest have all firmly planted their flags in the sand of the GKA class indicates that this is being seen as a potentially large and valuable new approach to diabetes.