Nine months on from reporting positive phase II data for its dual-acting SGLT1/2 inhibitor, LX4211, Lexicon Pharmaceuticals has yet to sign up a partner willing to undertake the cost of running its huge phase III programme in diabetes.
Yet the company insists that it is set to begin phase III in as many as 10,000 diabetics around the middle of this year, and has already discussed the study design with regulators and CROs. The hint therefore is that talks with prospective licensees are nearing the endgame, and there is much to suggest that the ideal partner could be Sanofi.
A focus for building a diabetes franchise has been to offer a range of drugs with different mechanisms of action, and several of the key players could add a late-stage SGLT2 inhibitor to their pipelines. In addition to Sanofi Merck & Co springs obviously to mind, but only Sanofi has already demonstrated its commitment in this direction.
The clue lies in a licensing deal that the French company quietly struck last October with Chugai (Roche) concerning a phase III SGLT2 inhibitor, tofogliflozin. Although the tie-up covered rights only in Japan, it made clear Sanofi’s interest in the SGLT mechanism.
Still, targeting diabetes through SGLT2 inhibition has had a rough ride, and the class has been associated with genitourinary infections.
Johnson & Johnson’s canagliflozin did recently secure advisory panel backing and could become the first SGLT2 inhibitor to reach the US market, ahead of Eli Lilly/Boehringer Ingelheim’s empagliflozin. AstraZeneca/Bristol-Myers Squibb’s dapagliflozin is available in the EU but was rejected in the US because of a possible breast and bladder cancer signal.
While inhibiting SGLT2 prevents glucose from being reabsorbed into the bloodstream in the kidneys, SGLT1 exerts its effect largely in the gut, and Lexicon says the 1 transporter subtype is responsible for mopping up post-prandial glucose. But inhibiting just SGLT1 has met with even less success, and the only molecule with this mechanism, GlaxoSmithKline/Kissei’s KGA-3235, has made slow progress.
This is where LX4211’s dual mechanism could come in. Lexicon insists that such a mechanism can have something of a complementary effect, for instance continuing to work in patients who lose renal function and thus no longer benefit from SGLT2 inhibition.
Importantly, the company’s phase II study showed impressive efficacy in lowering HbA1c, without an increased incidence of infections (Lexicon hopes data not words will win a partner, June 27, 2012). Lexicon has been ramping deal prospects, and LX4211 has featured prominently in recent investor conference presentations.
The company’s chief financial officer, Jeffrey Wade, recently said that the “objective has consistently been to have phase III funded by a partner”, at the same time as planning to begin the 10,000-patient pivotal programme in mid-2013.
Major diabetes franchise
So why not Sanofi? The French group is a major diabetes player with a franchise built around the basal insulin analogue Lantus; this has been fortified with Zealand Pharma’s GLP-1 agonist, Lyxumia, although development of a Lantus/Lyxumia combination has suffered a possibly terminal setback.
While a licensing deal with Lexicon for LX4211 could be just what the doctor ordered, Sanofi might have to outbid a company like Novartis, which appears to be the only other developer of a dual SGLT1/2 inhibitor, LIK066; Novartis would very likely be interested in LX4211 should LIK066 stumble. Neither Lexicon nor Sanofi responded to questions from EP Vantage regarding a possible tie-up.
Even if there is no counterbidder, price might be a sticking point. Given the SGLT class’s still unresolved safety issues, which might not arise until a large clinical trial, a heavily back-end-loaded alliance might be in order – which could be hard for Lexicon to stomach given the phase III-ready status of its project.
But whatever differences remain to be ironed out, Sanofi and Lexicon need to talk. If they have not done so already, deal bankers should get on the phones.