Boehringer Ingelheim GMBH and Eli Lilly & Co. announced positive top-line data for four pivotal trials testing empagliflozin, the sodium glucose co-transporter-2 inhibitor they are co-developing to treat type 2 diabetes, and said Lilly is on track to submit a U.S. marketing application in 2013.

While further data are being reserved for release in coming months at scientific meetings and in publications, the companies announced Jan. 7 that empagliflozin met the common primary endpoint of significant change in hemoglobin A1c levels in all four trials and that its safety profile was much the same in Phase III as in the Phase II results reported at the American Diabetes Association meeting in June 2012 Also see "Boehringer’s Smith Discusses The Challenges Of Diabetes At ADA" - Pink Sheet, 20 June, 2012..

The four trials evaluated both 10 mg and 25 mg doses of empagliflozin as monotherapy and in various combinations with standard type 2 diabetes medicines metformin, sulfonylurea and pioglitazone, as well as in type 2 diabetics with renal impairment.

The report of positive data is heartening, but the novel SGLT-2 class, once named a top medical innovation by the Cleveland Clinic, has yet to produce an approved drug. A bladder cancer signal and possible liver toxicity linked to Bristol-Myers Squibb Co./AstraZeneca PLC’s dapagliflozin, once the front-runner for first-in-class approval, are to blame for creating unease that those might be class effects Also see "Bristol Aims To Be First To Market With Novel Diabetes Drug Class" - Pink Sheet, 11 January, 2007..

Near-term trial results may dispel those larger fears, but genital infections are a known effect caused by the SGLT-2 mechanism of action. While other diabetes medicines aim to manage production of glucose, SGLT-2s block its reabsorption in the kidney, causing glucose to be flushed out in the urine and creating what might be called a more bacteria-friendly environment.

In diabetes, 2013 may be a breakthrough year for the SGLT-2 class, which has demonstrated glucose management efficacy but has not yet convinced FDA it is safe.

Despite its high marks for efficacy, benefit/risk doubts led FDA’s Endocrinologic and Metabolic Drugs Advisory Committee to vote against dapagliflozin’s approval, and Bristol received a “complete response” letter from FDA in January 2012 Also see "Dapagliflozin’s CV Profile Shines, But FDA Panel Review Falls On Cancer Concerns" - Pink Sheet, 25 July, 2011..

However, dapagliflozin’s fortunes may be about to change. Bristol announced during its third-quarter earnings call in October that it plans to resubmit the application for dapagliflozin, which it hopes to market as Forxiga, in mid-2013 with additional data from extension studies and that the company anticipates a new advisory committee hearing and a six-month review Also see "Bristol Signals Dapaglifozin’s Back On Track, Plans FDA Resubmission" - Pink Sheet, 1 November, 2012..

Meanwhile, the advisory committee is set to review the application for Johnson & Johnson’s SGLT-2 candidate canagliflozin on Jan. 10. Positive data from five Phase III studies of canagliflozin were presented at the ADA meeting in June Also see "J&J’s Canagliflozin Positive Phase III Data In The Limelight At ADA" - Pink Sheet, 11 June, 2012..

BI Loses Interest In Long-Acting Insulin

Lilly also announced on Jan. 7 that it was no longer partnered with privately held BI on development of Phase III LY2605541, a long-acting insulin that was part of a four-drug diabetes collaboration the two companies formed in January 2011 Also see "Lilly/BI Eye Diabetes Leadership In Expansive Risk-Sharing Collaboration" - Pink Sheet, 11 January, 2011.. BI said only that the decision was based on “independent strategic portfolio considerations.”

The collaboration will continue with empagliflozin, LY2963016, a new insulin glargine product, and the already approved dipeptidyl peptidase-4 blocker linagliptin, marketed in the U.S. as Tradjenta. Empagliflozin and linagliptin were brought to the collaboration by BI, a relative newcomer to the diabetes market, while Lilly’s strong suit is insulin, with its successful fast-acting Humalog (insulin lispro) and short-acting Humulin (recombinant human insulin) products.

Lilly will continue development of LY2605541, for which it is launching the remaining pre-planned clinical trials to support a regulatory submission for the product, meant to challenge Sanofi’s dominance of the long-acting market with Lantus (insulin glargine). At ADA, Lilly reported on four late-stage trials comparing LY2605541 to Lantus in both type 1 and type 2 diabetes, demonstrating improved glycemic control in type 1 patients and comparable control in type 2 patients. The Lilly product also may have a weight-loss benefit over Lantus and provide better glucose stability Also see "New Long-Acting Insulin Offerings Could Derail Lantus Franchise" - Pink Sheet, 18 June, 2012..

Lilly/BI Report Success For Oral Diabetes Drug, Adjust Alliance

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