Memorandum

GSK’s once-weekly albiglutide fails to meet non-inferiority endpoint of A1c reduction against Victoza though shows better tolerability – November 17, 2011

Executive Highlights

  • Albiglutide fails to meet the non-inferiority endpoint of A1c reduction vs Victoza in Harmony 7.

GSK just announced that its once weekly GLP-1 agonist albiglutide failed to meet the non-inferiority endpoint of A1c reduction against liraglutide (Novo Nordisk’s Victoza) in the Harmony 7 trial. The first of eight trials in albiglutide’s phase 3 program to report, Harmony 7 was a 32-week, open-label, non- inferiority study (n=841) in which patients on one to three oral anti-diabetic medications were randomized to receive either albiglutide 50 mg once weekly or Victoza 1.8 mg once daily. Those receiving albiglutide experienced an average A1c reduction of 0.78% from baseline, compared to an average A1c reduction of 0.99% with Victoza (baseline A1c was not reported). In addition, albiglutide brought about less weight loss than albiglutide – 0.62 kg (1.36 lbs) versus 2.21 kg (4.67 lbs). Meanwhile, tolerability with albiglutide was much improved compared to those receiving Victoza – 9.9% versus 29.2% nausea, and 5.0% versus 9.3% vomiting. This makes us wonder if dosing should be slightly higher though it would obviously be late in the game to be changing dosing. Initial results from the remaining seven phase 3 Harmony trials for albiglutide are expected within the next few months; the primary efficacy endpoint for all eight trials should be complete by mid-2012.

We find it interesting that both once weekly GLP-1 agonists (albiglutide and Bydureon) studied head-to- head with Victoza have demonstrated poorer glycemic control and weight-loss efficacy but improved GI tolerability versus the once-daily drug. Although we are curious as to why albiglutide and Bydureon demonstrated poorer efficacy in their respective clinical trials, we wonder whether the more continuous exposure provided by both once-weekly drugs will result in improved glycemic control in real-world settings. We also believe that patients and healthcare providers will appreciate the increased convenience of a once-weekly formulation (especially if an easy-to-use delivery device is available) and the drugs’ improved tolerability should be a big plus. In comparison to Bydureon, it remains to be seen what would differentiate albiglutide. To our knowledge, no head-to-head studies are currently planned. Bydureon, however, will likely have several advantages over albiglutide – in all likelihood, Bydureon would have been on the market for well over a year (we continue to expect approval around January 28, 2012) and would likely be available in a dual-chambered pen device (Amylin management has guided for late 2012 – early 2013) by the earliest possible date albiglutide could be approved (mid-2013 by our estimates in the best case). Amylin will also be able to draw from extensive market experience with exenatide (Byetta has been available since 2005) as well as an established sales staff that is already familiar with GLP-1 in its marketing efforts. As such, we hypothesize that aggressive price and sales/marketing efforts may be necessary for albiglutide to gain significant traction in the GLP-1 marketplace. In addition to albiglutide, other once-weekly GLP-1 agonists currently in development include: Lilly’s dulaglutide (LY2189265; phase 3 expected to complete in late 2012), Novo Nordisk’s semaglutide (NN9535) and once-weekly liraglutide (Novo Nordisk plans to select one candidate to advance into phase 3 by mid-2012), and PhaseBio’s Glymera (phase 2). Intarcia also has an extended duration product in development (phase 3).

Close Concerns Questions:

Q: Were any effects on CV biomarkers observed?

Q: What gauge needle is used?

Q: Is albiglutide a soluble formulation?

Q: Will a pen device be available upon possible approval?

-- by Vincent Wu, Ben Kozak and Kelly Close