Significant developments amongst the turbulent class of GLP-1 agonist diabetes drugs occurred today with fittingly mixed performances. Good news came from Sanofi-Aventis and Zealand Pharma, who reported encouraging head-to-head pivotal data for their candidate lixisenatide against Byetta, while quarterly sales of Novo Nordisk’s Victoza continue to exceed expectations.
Conversely, Ipsen was feeling the punch after partner Roche handed back rights to dogged candidate taspoglutide; though widely expected, Ipsen’s shares still slipped 7% today to €23.76. The likely loss of taspoglutide and setbacks to Amylin Pharmaceuticals and Eli Lilly’s Bydureon, means the GLP-1 space is not quite the über-competitive market it might once have been, handing an opportunity to the likes of lixisenatide and GlaxoSmithKline’s Syncria (see table below).
Non-inferior, assume not superior
Once-daily lixisenatide met its primary endpoint in the phase III, open-label Get-Goal-X trial, demonstrating non-inferiority to twice-daily Byetta in its capacity to reduce HbA1c – glycated haemoglobin, a measure of plasma glucose concentration – in 639 type 2 diabetics.
The drug also reduced the incidence of complications associated with low blood sugar, symptomatic events and hypoglycaemia.
A full data set, likely to emerge at the American Diabetes Association meeting in San Diego in June, will to a certain extent allow lixisenatide to be held up to Victoza as both have been tested versus Byetta in various separate studies, so their relative performance can be assessed. No trials comparing lixisenatide with Victoza have been initiated.
Lixisenatide is undergoing ten pivotal trials, four of which are fully complete, and a stream of topline results are expected over the next few months; the Get-Goal-X trial was the only head-to-head study against a GLP-1 agonist.
Lixisenatide is expected to launch late next year outside of the US, with a US launch to follow in the second half of 2013.
Swedish bank SEB Enskilda wrote today that it reckons there is room for another GLP-1 agonist in a space currently occupied by Byetta and Victoza, and predicts lixisenatide is next in line for approval.
Bydureon developers Eli Lilly and Amylin Pharmaceuticals are expected to respond to the FDA’s requests for additional safety data by the end of the year (FDA crashes party of three with Bydureon rejection, October 20, 2010). This resubmission is likely to lead to a 6-month review, meaning Bydureon’s US approval and launch timeline would be slightly ahead of lixisenatide. In its fourth quarter statement Amylin reckoned it had sufficiently addressed the FDA’s requests, and the regulatory process is back on track.
Jefferies has pencilled in worldwide peak sales of $650m for lixisenatide – or 15% market penetration – compared with EvaluatePharma consensus at $251m in 2016.
While the data so far on lixisenatide signals the drug's potential as a monotherapy, the real market winner could be a combination therapy with Sanofi’s basal insulin product Lantus. Described by Jefferies as a potential “paradigm shift in type 2 diabetes treatment”, pivotal trials should start this year, and peak sales as a combination product could reach $1.3bn, with a launch in the second half of 2014 predicted. Novo is also chasing this strategy, announcing today two large trials combining its new insulin, degludec, with Victoza.
Once-weekly the victor
ISI analysts said today they expect once-weekly versions, like Bydureon and Glaxo's Syncria, to eventually emerge victorious, presumably on the grounds of patient compliance.
Incidentally, Novo Nordisk said today it is delaying its decision until mid-2012 on which of its own once-weekly candidates to pursue: either a once-weekly formulation of Victoza or new candidate, semaglutide.
Meanwhile Glaxo’s Syncria should report pivotal head-to-head data against Victoza by year-end. A launch by late 2012 or early 2013 is feasible, again expected to follow hot on the heels of Bydureon.
As a key player in the GLP-1 agonist space, Novo Nordisk reported other significant developments as part of its fourth quarter statement.
Firstly, sales of Victoza are exceeding expectations. It reported $415m in 2010 sales, versus consensus estimates of $300m. EvaluatePharma sees worldwide Victoza sales reaching blockbuster status by 2013, and generating $1.5bn in 2016.
Meanwhile the company has scrapped development of an oral GLP-1 agonist NN9925, on the basis of bioavailability; the phase I candidate was being developed using Merrion Pharmaceuticals' technology. Another oral candidate, NN9924, in development with Emisphere Technologies, remains on track.
With Roche having returned rights to taspoglutide, the future of the once-weekly GLP-1s hang in the balance. Ipsen has confirmed it will not continue development without a partner, but the safety concerns of nausea and hypersensitivity that have emerged suggest taspoglutide is not an attractive prospect (Taspo suspension appears terminal, September 13, 2010).
Ipsen will provide more clarity on its next steps in a conference call tomorrow, with a full strategic update from chief executive Marc de Garidel expected next quarter (Ipsen turnaround awaited as pipeline setbacks mount, December 16, 2010).
The likely loss of taspoglutide could be good news for other GLP-1 agonists, although the expected launch of Bydureon still looks a big competitive threat for lixisenatide and Syncria.
|GLP-1 agonist market|
|Annual WW sales ($m)|
|Product||Generic Name||Company||Dosing||Phase (Current)||2010||2012||2014||2016|
|Bydureon||exenatide||Amylin Pharmaceuticals + Eli Lilly||Once weekly||Filed||-||197||970||1,618|
|Victoza||liraglutide||Novo Nordisk||Once daily||Marketed||300||942||1,339||1,564|
|Syncria||albiglutide||GlaxoSmithKline||Once weekly||Phase III||-||24||193||382|
|Lixisenatide||lixisenatide||Sanofi-Aventis + Zealand Pharma||Once daily||Phase III||-||51||163||251|
|Byetta||exenatide||Amylin Pharmaceuticals + Eli Lilly||Twice daily||Marketed||710||518||304||227|
|LY2189265||dulaglutide||Eli Lilly||Once weekly||Phase III||-||-||9||50|
|NN9535||semaglutide||Novo Nordisk||Once weekly||Phase II||-||-||12||49|