Takeda announced positive late-stage results for its new type 2 diabetes drug, fasiglifam (TAK-875), the first GPR40 agonist to reach late-stage development.
Fasiglifam has the potential to be a compelling therapeutic option and will likely be investigated for use in combination therapy, given its unique mechanism of action. The Japanese drug maker is in desperate need of reviving its diabetes franchise now that its blockbuster drug, Actos (pioglitazone), fell off the patent cliff in August 2012 and has since been subject to strong generic erosion. Actos accounted for about 18% of Takeda’s 2011 revenue, and the company now faces a significant profit loss over the next few years. Could fasiglifam as a first-in-class drug become Takeda’s new potential blockbuster in 2014–2015, when its launch is expected?
Nothing is as exciting as a first-in-class molecule in the pipeline. We have witnessed several of these in the type 2 diabetes space that have had enormous success and have achieved blockbuster status. However, how long will it be until the market becomes too saturated with drugs having a novel mechanism of action, if those drugs are no longer bringing a high degree of differentiation in terms of addressing the greatest unmet clinical needs in type 2 diabetes, such as sustainable glycemic control? GPR-40 agonists, being glucose-dependent insulin secretagogues, do not address insulin resistance and the decline in cell function, the roots of type 2 diabetes.
We are entering an era in the diabetes market where the first-in-class drugs start in many ways to resemble “me-too” drugs, despite their novel mechanisms of action. With some of the diabetes drugs going off patent, the prospect for future diabetes blockbusters becomes even bleaker due to eventual generic competition to the former blockbusters, and consequently, even more pronounced cost-effectiveness issues.
With or without future blockbusters, the type 2 diabetes market is huge and is growing rapidly. Therefore, Takeda, as an established diabetes player, will certainly find a way to keep a significant market share. The company is currently also preparing for a Phase III study to evaluate the efficacy and safety of fasiglifam in combination with sitagliptin (Januvia), Merck’s blockbuster drug.
GlobalData believes that this combination holds great potential due to Januvia’s popularity, and also given each drug’s distinct mechanism of action, oral route of administration, and good safety profile. Through the partnership with Furiex Pharmaceuticals, Takeda’s diabetes portfolio has been recently strengthened by Nesina (alogliptin) and the approval of its two fixed-dose combination drugs, Oseni (alogliptin + pioglitazone) and Kazano (alogliptin + metformin), in Japan and in the US.
However, as the fifth to the market, Nesina will grab only a tiny slice of the dipeptidyl peptidase-4 (DPP-4) inhibitor space. Takeda and Furiex are also partnered on trelagliptin (SYR-472), a long-acting DPP-4 inhibitor that is in late-stage development in Japan. Fasiglifam, together with all these contenders in Takeda’s pipeline, will contribute to the revival of the company’s diabetes business in the post-Actos era; however, the golden times are unlikely to return in the foreseeable future.
I would not call a GPR40 agonist a "me-too" drug as GPR40 is a novel molecular target, and its mechanism to trigger glucose-dependent insulin secretion must be at least partially distinct from that used by GLP-1 analogs or DPP-IV inhibitors.
However, I agree with you that this mechanism of action (pushing insulin secretion) does not seem to address the insulin resistance that is the major cause of type 2 diabetes (in most patients). As such, GPR40 agonists, like all current diabetes drugs, won't have an impact on the evolution of the disease. They will just prevent complications.
Olivier Boss, PhD (Energesis Pharmaceuticals)