Novo Nordisk put out an impressive press release early this morning showing superiority of its GLP-1 liraglutide vs Lantus (glargine, Sanofi). We believe results are significant and that the GLP-1 franchise will expand as a result of Novo Nordisk’s entry into the market, likely ~late 2009/early 2010.
Quick takeaways: 1) The six-month trial enrolled 581 patients failing dual oral agent therapy (maximum dose, metformin and SFU) and randomized patients to one injection of either liraglutide, Lantus, or placebo. Starting A1cs were 8.0% to 8.5% (average 8.3). 2) At the end of the study, over 50% of those in the liraglutide group were at an A1c of less than 7% and over 35% were less than 6.5%. We view these numbers as impressive given the high number of type 2 patients not at their glycemic targets. 3) Tolerability was impressive, with just 10-15% of patients experiencing nausea. Moderate and severe hypoglycemia was ~40% - we will be eager to hear more about hypoglycemia, especially severe hypoglycemia. 4) Needle gauge was 31 for syringes patients used to take both liraglutide and Lantus. We view this as quite positive for once-daily use. 5) Ultimately, for this trial, we were surprised that an A1c difference of 0.2% between the groups was statistically significant, but we were impressed that Novo was able to show something beyond non-inferiority, which is presumably what the company had been looking to prove. As noted, we will be eager to see more about trial design, but on a preliminary basis, we would term the finding that liraglutide is superior to insulin as striking. 7) We believe Novo will try to position Liraglutide broadly, for use as monotherapy, as a replacement for oral agents, and for use before insulin. Ultimately, we believe Novo will also look for indications for liraglutide to be used with insulin and for use in obese non-diabetic patients. Interest in liraglutide for obesity has been significant and as we understand it, obesity studies are progressing quickly. 8) We view this news as a positive for Novo, assuming trial design doesn’t show any major surprises, a negative for Sanofi (due to liraglutide's superiority, even slightly significant, over Lantus), and neutral for Amylin – the latter because although this compound could compete strongly against Byetta, we believe Amylin’s LAR will have a very strong entry into the diabetes marketplace. There is room for two, if safety etc pans out. Ultimately, this news is less about likelihood of stealing GLP-1 market share and more about a compound that could significantly expand the GLP-1 marketplace – particularly given the commitment (to say nothing of marketing prowess) of Novo Nordisk to date. We look forward to listening to the conference call on this topic, which starts in 30 minutes. Our questions:
1. How much weight did Lantus and placebo groups gain vs. the liraglutide group lost?
2. What were exact starting and ending A1cs for the groups? How much variability in ending A1c?
3. What were the p-values associated with the A1c difference and the weight loss?
4. Were 7-point profiles done? Is there data on fasting and post-prandial they will give?
5. What were hypo rates - moderate and severe? How was hypoglycemia defined?
6. How aggressively was Lantus titrated?
7. What kind of counseling was offered on diet and exercise?
8. What can they say about beta cell protection and regeneration?
9. What is the timing for an obesity indication, given it is now in phase 2?
10. If all trials will be done by the first quarter of 2008 (four more trials in the next 8-9 months), what are the chances they will submit in late 2008?
11. For which indications will they submit? Metformin, SFU, TZD, Monotherapy, and insulin?
12. Could Lira be positioned as once every two days rather than once/day? We understand from PIs in Barcelona this is possible (though not probable as a recommendation). How far are they in exploring other doses like once weekly?