GLP-1s' first outcomes study unlikely to lift Lyxumia

As a late entrant to the GLP-1 agonist market Sanofi needs all the help it can muster for diabetes drug Lyxumia. So news that a 6,000-patient outcomes study has not detected any sign of a link between the product and an increased risk of cardiovascular problems is encouraging; at the very least it means the French pharma giant can push on with a much-delayed US filing.

The big win, of course, would have been signals of cardio-protective benefits. These seem not to have emerged, although this was considered a long shot. As such, Lyxumia looks destined to retain its status as an also-ran in a fast growing market (see sales forecasts below).

Only top-line results from the Elixa study were released and these showed that Lyxumia was non-inferior, although not superior, to placebo for cardiovascular safety, according to Sanofi.

Although the study failed to detect any evidence of a benefit, the importance of ruling out risk should not be underestimated, even though this was the expected outcome. Low-level concerns about the cardiac impact of this class – specifically increased heart rate – and heightened awareness of safety in the diabetic population more generally prompted the FDA to insist on these studies in high risk populations as a condition of approval for all the GLP-1 agonists.

Sanofi’s is the first to report; the next is likely to be Novo Nordisk’s Leader study, probably at the beginning of next year.

The possibility of one of these agents differentiating itself on either safety or cardiac benefit remains. So although many operators in this space will be relieved to see the Elixia result today, the remaining readouts will still be keenly awaited.

And so will the full results from Elixia, which will be presented on June 8 at the ADA annual conference. The primary endpoint was time to occurrence of the first primary cardiovascular event; secondary endpoints also looked at other co-morbidities like heart failure and coronary revascularisation.

With no information released on these measures, Sanofi will be hoping to find something in the data set on which to hang unique marketing messages for the drug.

Consensus data from EvaluatePharma shows how urgent this need is. Equity analysts do not rate the product’s prospects particularly highly in comparison with rivals, although it should be remembered that the majority of these have a substantial head start, particularly in the crucial US market, and the Lantus combination product LixiLan could still prove to be a more important growth driver for the franchise in the future.

Rueing the decision?

Sanofi now intends to re-file Lyxumia in the third quarter, making a launch next year highly probable. It withdrew its initial filing in September 2013, saying it wanted to protect the integrity of the Elixia result, interim data from which could have emerged as part of the application process (Sanofi’s surprise Lyxumia move raises stakes for CV outcome study, September 12, 2013).

At the time this was considered a surprising decision and prompted speculation that it was made to avoid a situation whereby the FDA turned down the application pending the full outcome data. However, the regulator has since approved both Tanzeum and Trulicity, neither of which had generated outcome data; GlaxoSmithKline has yet to even start its study for Tanzeum.

So Sanofi is left with a late product that cannot launch with a claim of cardio-protective benefits. Unless it can find something unique to talk about in the full data set, it may yet come to rue passing on valuable extra months on the US market.

To contact the writer of this story email Amy Brown in London at [email protected] or follow @AmyEPVantage on Twitter