Memorandum
There has been recent speculation that Novo Nordisk will release a verdict (likely a positive one) on its go/no-go decision to move forward with phase 3 trials for an oral formulation of the GLP-1 agonist semaglutide by their 1H15 update on August 6, 2015. This is slightly earlier than the end-of-year deadline for the decision provided by Novo Nordisk in their 4Q14 update in January and we’ll be watching and listening closely to see if this happens! Manufacturing and commercialization costs represent major considerations in the decision to proceed into phase 3, of course; language from CEO Mr. Lars Sørensen in the 4Q update suggested that initial cost analyses have been positive, though investing in the necessary manufacturing capacity will be quite an undertaking. As a reminder, topline phase 2 results released in February demonstrated strong efficacy (mean A1c drop from 7.9% to 6.0% with the oral and injectable formulations – that’s a massive drop from a low A1c base) and safety, with nausea slightly higher with the highest-dose oral formulation vs. the injectable. Novo Nordisk’s oral semaglutide uses Emisphere’s SNAC enhancer as a carrier in its delivery mechanism. As we noted in our Novo Nordisk 1Q15 Report, cost-effective commercialization is a challenge, given that oral semaglutide requires a 280x (!) dose to match the efficacy of the injectable version. Management has suggested phase 3 trials could potentially begin in 1H16, placing the commercialization timeline roughly around 2019-2020, in time to catch Victoza’s patent expiry in 2023. Novo Nordisk is currently the only company to have completed phase 2 trials for an oral GLP-1 agonist; Oramed will begin phase 2 trials of its oral exenatide later this year and TransTech Pharma’s oral GLP-1 agonist formulation is currently in phase 2 trials. We’ll be watching closely for news on the side effect profile – this impacts, of course, how easy it would be for HCPs to prescribe and patients to take the drug. In the “real world,” it has been harder to teach good ways to manage the side effect profile (particularly nausea) compared to how well HCPs did this in the randomized clinical trials (where often the educators and doctors were very well trained and had lots of experience handling this particularly adeptly).