Event – Novo looks to Sustain GLP-1 leadership with semaglutide

If ever Novo Nordisk needed clinical trials to come good, it is those in the Sustain programme testing its next-generation glucagon-like peptide-1 (GLP-1) agonist semaglutide.

The Danish group is seeing the position of its first entry, the daily injection Victoza, chiselled away as new competitors enter the space, most significantly the once-weekly injection Trulicity. Analysts and investors already assume a clinical win for weekly semaglutide, an outcome that will also be necessary for Novo to defend its GLP-1 leadership through a transition to oral delivery.

Data from the phase III Sustain-1 trial due in May will come in the context of belt-tightening in all aspects of diabetes care, from on-patent oral drugs to insulin. As payers make way for a wave of expensive new agents in specialised diseases, drugmakers are under pressure to cut prices used for common conditions (Diabetes warning sends Sanofi stumbling, October 28, 2014).

Sustaining a franchise

Sustain-1 is the first of eight clinical trials, which have enrolled a total of 8,000 patients, expected to report data on semaglutide. It tests the once-weekly injections as a monotherapy against placebo in 390 diabetics who have never before been treated for the condition, measuring the usual change in blood sugar readings as a primary endpoint.

This is a fairly low bar to leap as there is no active comparator like Trulicity or other background antidiabetic drugs to confound data – if semaglutide does not work in this setting it ought to cast doubt on any success in the remaining trials.

These are set to read out from mid-2015 through early 2016, with the biggest being the 3,200-patient Sustain-6 cardiovascular outcomes study, expected around the beginning of next year. This should be an essential one to the filing given that Novo has tripped up previously with regulators on cardiovascular data; its long-acting insulin Tresiba has been delayed to the US market by more than two years to satisfy cardiovascular risk concerns.

If successful, semaglutide would join Victoza in Novo’s market-leading GLP-1 franchise and would protect its flank against Lilly’s Trulicity, launched last year as the first weekly drug strengthened by data showing it to be the equal of Victoza in lowering blood sugar.

Victoza is forecast to retain its position as the biggest-selling GLP-1, but its market share peaked at 73% in 2013. Its 2020 consensus forecast has fallen by 13% in less than a year and now stands at $3.6bn, according to EvaluatePharma. Payer pressure has played a role – the market now has not only a more convenient option in Trulicity but also a lower-cost choice in GlaxoSmithKline’s Tanzeum.

Thus semaglutide will be necessary to boost Novo’s growth in this drug class. Bernstein analyst Ronny Gal calls it a “must succeed” programme and the investment community assumes it will – the consensus forecasts $680m in sales in 2020. Success will probably not generate much of an investor reaction, but a setback in the Sustain programme would likely see a fall in share price.

From jab to pill

Sustain’s success should also be a green light to advancing Novo’s oral semaglutide project, now code-named NN9924 or OG217SC. Oral delivery would represent an advance over current products and would generate sales growth not now forecast by analysts; but this is a much more risky project.

Mr Gal writes that Novo is up against a difficult biological challenge in ensuring that a peptide can consistently cross from the digestive tract to the bloodstream every day in every patient, making its success far from assured. Phase I data from 11 patients showed a reduction in blood sugar, but results from a phase II dosing trial in more than 600 patients that wrapped up in December will be more revelatory.

“Our view is that if Novo is successful with oral semaglutide, it would be their most important drug in the next 10 years,” Mr Gal writes.

Some analysts expect Novo's scientists to be up for this challenge – Bank of America-Merrill Lynch reckons DKr750m ($117.4m) in sales in 2023 and Citi DKr1.1bn in 2024. As Mr Gal writes, a company less experienced in peptide technologies would not be given nearly as much of a chance.

To contact the writer of this story email Jonathan Gardner in London at [email protected] or follow @JonEPVantage on Twitter