On the heels of showing its popular diabetes med semaglutide holds potential in non-alcoholic steatohepatitis, Novo Nordisk is now touting the first clinical win for the GLP-1 med in obesity—a tough market it's bet big on.
Over a total treatment period of 68 weeks, once-weekly semaglutide resulted in an average weight loss of 17.4% among people in a phase 3a trial, whereas those who received a dummy drug after a 20-week lead-in phase saw their body weight rebound by 6.9% during the rest 48 weeks, the Danish drugmaker unveiled on Wednesday.
Among those who were compliant and didn’t take any other anti-obesity therapies, semaglutide’s benefit became more pronounced, triggering an average weight loss of 18.2%.
Double-digit weight loss is hard to provoke. Saxenda, currently the world's best-selling obesity drug and a sister formulation of Novo's older GLP-1 diabetes med Victoza, achieved 4.5% improvement over placebo in patients without diabetes and 3.7% in those with diabetes at the one-year mark. Roche's Xenical, which is also available over-the-counter, achieved 11.4 kg weight loss at one year when used alongside lifestyle intervention, a small improvement over the 7.5 kg reduction seen with lifestyle intervention alone.
And it's exactly the kind of results Novo wants to see. The Danish drugmaker—apparently not scared off by major commercial flops from the likes of Vivus, Arena and Orexigen—is betting big on obesity as a way to diversify beyond the still-tough diabetes market, having set up a new R&D center in Seattle focused on early discovery projects within the diabetes and obesity areas.
In its 2019 annual report, the company outlined an ambition to double its obesity sales by 2025. And semaglutide will need to play a major part in achieving that goal as Saxenda is slated to go off patent protection around 2023.
The STEP 4 trial is the first completed study of four in the clinical trial program testing semaglutide as an obesity drug. The other three trials testing the drug alone or in combination with intensive behavioral treatment in overweight people with or without diabetes will also read out in the following months.
In the study, 902 people with obesity first took weekly under-the-skin semaglutide at increasing dosage strengths for 20 weeks. Then, 803 people who reached the target maintenance dose of 2.4 mg were randomized to either continue treatment or placebo for 48 weeks.
At the point of randomization, all patients’ mean body weight had dropped to an average 96.1 kg from 107.2 kg at baseline. But during the following 48 weeks, those who stayed on semaglutide enjoyed further mean weight loss of 7.9%, while people on placebo regained 6.9% of the weight. The study is designed this way to show a “withdrawal” effect of discontinuing treatment after a few months, as compared to staying on for a year, Novo Nordisk’s chief science officer Mads Krogsgaard Thomsen said during a company conference call last week.
“STEP 4 shows that people continuing treatment with semaglutide achieved a further substantial weight loss while people switching to placebo, on the other hand, regained a significant amount of weight,” Thomsen said in a statement Wednesday.
Semaglutide is a next-generation GLP-1 drug currently sold as a once-weekly injectable at a lower dose in blockbuster diabetes drug Ozempic, and also in a newly approved oral formulation as Rybelsus.
Novo’s obesity franchise currently consists of Saxenda, which the company said makes up of 56% of the global obesity prescription drug market as of 2019. Last year, Saxenda sales jumped 47% to DKK 5.68 billion ($823 million).
The positive obesity readout follows closely that of a phase 2 trial of semaglutide in NASH. That NASH study showed that a significantly higher percentage of patients on the drug saw NASH symptoms resolve without worsening in liver fibrosis than placebo patients did. Though the phase 2 patients were on daily semaglutide injections, Novo has decided that it will turn to a once-weekly regimen moving into phase 3. During the conference call, Thomsen suggested that it might apply the same dosing titration regimen in the obesity trial—namely starting from 0.25 mg, as is the case with Ozempic, all the way up to 2.4 mg—for NASH.
Both NASH and obesity are potential multibillion-dollar markets.