Event – Lilly stands on diabetes franchise to climb from trough

With the patent expiry of its biggest seller, Cymbalta, last month, Lilly knew 2014 was going to be a testing year, an outlook it confirmed yesterday when outlining its annual guidance. A big part of climbing out of its trough year will be two additions to its diabetes franchise, both of which have key dates coming up.

An FDA action date on the Boehringer Ingelheim-partnered empagliflozin is due within weeks, and the decision could allow the two companies to break into the increasingly competitive space for sodium-glucose cotransporter-2 (SGLT2) inhibitors. Equally important could be readout of the head-to-head trial of dulaglutide against Novo Nordisk’s Victoza, which has proven itself resilient against such challenges in the past.

Not a sure thing

While empagliflozin has not been subject to the scrutiny of an advisory committee, often taken as a sign of regulatory comfort, the SGLT2 class has seen its share of knockbacks from the FDA. The very first candidate in the class to reach the regulator, AstraZeneca’s Farxiga, was rejected on its first pass. Johnson & Johnson’s Invokana got a thumbs-up the first time through, and this is certainly what Lilly will be hoping for when the FDA makes its decision sometime in the first quarter.

In general, the safety worries about the class stem from the increase in glucose excreted in the urine, the mechanism through which the SGLT2s reduce blood sugar. This has been tied to genitourinary infections. Farxiga (dapagliflozin) was held up over a cancer signal, a risk with which the FDA has grown comfortable as it approved the pill today (Panel’s thumbs up for dapa a glimmer of good news for Astra, December 13, 2013).

Empagliflozin is part of a 50-50 global profit-sharing deal signed in 2011 with Boehringer Ingelheim, and is reckoned to be worth $39m in revenue for Lilly in 2014, a sum that will rise to $354m in 2018, according to EvaluatePharma’s consensus forecasts. Alone, this will not offset the loss in revenue from Cymbalta, expected to plummet from $5.2bn last year to $1.5bn in 2014.

It will be useful income, however, in a “trough” year that executives of the Indianapolis-based group have long anticipated. Topline revenue is expected to drop from $23bn in 2013 to $19.2-$19.8bn this year, although this is somewhat dependent on its pipeline hopes, like empagliflozin, coming through.

Sales in the SGLT2 class expected to be among the more modest of the novel drugs in diabetes, as the leading drug, canagliflozin, might only achieve blockbuster status in 2018, five years after launch.

Taking on the champ

So equally important for 2014, and perhaps of greater importance over time, is dulaglutide. This is a glucagon-like peptide 1 (GLP-1) agonist, a class that has probably exceeded expectation thanks to the performance of Victoza.

As a once-weekly, the Lilly entry has an obvious dosing advantage, but this is a contest the once-daily Victoza has won before, when once-weekly Bydureon, a GLP-1 to which Lilly once held commercial rights, failed to show non-inferiority (Amylin scores own goal in Bydureon vs Victoza head-to-head study, March 3, 2011).

So far, Lilly’s Award clinical programme has shown that dulaglutide, either alone or in various combinations, is superior or non-inferior to diabetes treatments ranging from Byetta to the long-acting insulin Lantus when it comes to controlling blood sugar. Tantalisingly, the Award-6 head-to-head with Victoza is one of three trials yet to report, expected in the first quarter, with full data likely available at the American Diabetes Association meeting in June.

A showing of non-inferiority would certainly put it on an even footing with Victoza, especially given its dosing advantage, and superiority would clearly give dulaglutide the upper hand.

Although Lilly's cancer project ramucirumab has drawn a lot of the late-stage attention, dulaglutide could very well be more important in this trough year – it has a forecast of $102m in 2014 to ramu’s $45m, according to EvaluatePharma’s consensus, although the ImClone-originated antibody will just about draw even in 2018 with $726m in sales to dulaglutide’s $831m.

Lilly has one of the oldest diabetes franchises in the world, and despite the attention paid to some of its emerging cancer treatments it is no surprise to see it relying on its mainstay in a difficult year.

Trial Setting ID
Award-6 Dulaglutide head-to-head with Victoza NCT01624259

To contact the writer of this story email Jonathan Gardner in London at [email protected] or follow @JonEPVantage on Twitter

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