Despite the rough treatment of Sanofi’s LixiLan in adcom briefing documents, both this and Novo Nordisk’s rival diabetes combo Xultophy have managed to secure the US panel’s backing, setting them on course for likely FDA approvals this summer.
However, differences in panellists’ comments reinforce the view that Novo has the upper hand, even before considering that Xultophy, but not LixiLan, is already approved in the EU. And consensus forecasts show that notwithstanding Sanofi’s best efforts LixiLan is too little and comes too late to save the French group’s diabetes franchise.
Sellside expectations, as compiled by EvaluatePharma, show Xultophy selling $2.8bn in 2022 versus LixiLan’s $1.1bn. If the Sanofi combo is approved this will have come after a long history of delays, and Sanofi’s diabetes franchise is set to be rocked by this year’s launch of a biosimilar version of Lantus, LixiLan’s insulin analogue component.
Still, Sanofi shows no sign of giving up: to cut LixiLan’s US review time from 10 months to six and catch up with Novo it redeemed a priority review voucher that it had bought from Retrophin for $245m. LixiLan’s GLP-1 agonist component, lixisenatide, is also awaiting US approval (Sanofi’s positive result in LixiLan-O comes a little too late, July 29, 2015).
Votes in favour
The US adcom vote in favour of LixiLan, by a 12 to two margin, came after market close yesterday, a day after the panel unanimously recommended Novo’s Xultophy – a combination of Victoza and Tresiba.
Diabetes stocks have crept up in the past three days – Novo and Sanofi rising 5%, and Sanofi’s lixisenatide partner, Zealand Pharma, enjoying a three-day climb of 15%. Sanofi had wobbled on the May 23 release of briefing documents suggesting increased scrutiny over lack of dosing flexibility, and possible mistakes due to design of the injector pen.
Lack of flexibility was also a concern with Xultophy, but in the event the panellists came down on the side of approval. A separate consideration with both combos was whether they should be used in patients who are still naive to both of their respective components.
Panellists seemed doubtful over LixiLan in this setting since the combo delivers a lower dose of the GLP-1 element than the standalone drug, and thus sequential use of its standalone ingredients seemed more appropriate. Xultophy, on the other hand, could benefit certain naive patients, the adcom suggested.
An issue that the FDA will decide is post-approval studies, which for LixiLan might have to look into anaphylaxis, antibody responses and effect on extremely obese patients. There was a suggestion that Xultophy’s benefit beyond 26 weeks needed to be quantified.
|Eating into Sanofi's diabetes franchise|
|Name||Mechanism||2015 sales ($m)||2022e sales ($m)||Note|
|Tresiba||insulin degludec||214||2,910||Marketed in EU & US|
|Victoza||GLP-1 agonist||2,682||4,099||Marketed in EU & US|
|Xultophy/IDegLira||combo of above||0||2,839||Marketed in EU; US PDUFA Jul 2016|
|Lantus||insulin glargine||7,089||2,960||US biosimilar approved, due for launch Dec 2016|
|Lyxumia||GLP-1 agonist||42||327||Marketed in EU; US PDUFA Jul 2016|
|LixiLan/IGlarLixi||combo of above||0||1,050||US PDUFA Aug 2016|
If the FDA follows the panel’s recommendations the Novo and Sanofi products should receive approval by action dates in July and August respectively; standalone lixisenatide, marketed in Europe as Lyxumia, has a July PDUFA date.
Whatever the agency’s verdicts, and in whichever order they come, the panel deliberations and sellside consensus reveal just how much ground Sanofi has lost in diabetes, and how much it needs to make up through business development. Yesterday Sanofi moved to replace Medivation’s board with its own slate of directors in a bid to force the company to the negotiating table.
At least the French group knows it needs to act, even if it still refuses to accept that to buy Medivation it needs to pay much more than it presently seems willing to.