Zealand Pharma is lining up a challenge to its compatriot Novo Nordisk. The Danish biotech’s CEO said obesity candidate petrelintide can be “the backbone of therapy for weight management” after reporting phase 1b data that suggest it may provide GLP-1-like efficacy without the side effects.
Petrelintide is a long-acting amylin analog. Novo, which led the way in GLP-1 with Ozempic and Wegovy, also has an amylin analog, cagrilintide, in clinical development. Zealand sees petrelintide as a potential best-in-class amylin analog and presented the phase 1b data to make its case.
The phase 1b study randomized 48 adults with overweight and obesity to receive one of three doses of petrelintide or placebo for 16 weeks. The median baseline BMI was 29, on the low side for weight-loss trials, and most participants were male, who typically lose less weight than females on GLP-1 drugs. Dose titration meant subjects on the top two doses spent six to eight weeks on the maintenance dose.
After 16 weeks, Zealand saw mean reductions in body mass of 8.6% and 8.3% in participants on the two higher doses. The figure for the placebo arm was 1.7%. Subjects seemed to be continuing to lose weight when the trial ended, boosting the biotech’s belief petrelintide can reach the 15% to 20% range achieved by GLP-1 drugs.
“We see no evidence of an early plateau in the treatment response,” David Kendall, M.D., chief medical officer at Zealand, said on a call with investors. “As has been reported with cagrilintide and was seen previously with petrelintide, we would anticipate progressive weight loss over a period in excess of one year. The regulatory requirements now provide an opportunity to look out beyond 76 weeks of therapy.”
GLP-1-like efficacy is one part of the pitch for petrelintide. Gastrointestinal tolerability is the other part. Some people experience nausea and other gastrointestinal symptoms while taking GLP-1 drugs. Zealand is pitching petrelintide as a potential option for patients who cannot tolerate GLP-1 meds and to people who want an alternative, more tolerable treatment for maintaining weight lost on drugs such as Wegovy.
Zealand saw two moderate gastrointestinal adverse events in the phase 1b trial. The events, nausea and vomiting, affected one participant who stopped treatment after the third dose. All other gastrointestinal events were mild. No other subjects discontinued treatment due to adverse events or reported vomiting. There were two reports of mild diarrhea.
Nausea was reported by up to 33.3% of people on petrelintide, compared to 16.7% of their peers on placebo. Kendall said that “the vast majority [of nausea cases] were transient and there was a significant decrease in the reported rates of nausea over the course of treatment.”
Shares in Zealand jumped 20% in the wake of the data drop, climbing to 775 Danish kroner in early trading in Copenhagen on Friday.
Encouraged by the data, Zealand is working to start a phase 2b trial in the second half of the year. The trial will randomize more than 400 adults with overweight or obesity to receive placebo or various doses of petrelintide for 42 weeks. Zealand has picked percentage change in weight as the primary endpoint and will also look at muscle preservation, an area it believes it may have an edge over GLP-1 drugs.
Zealand CEO Adam Steensberg, M.D., said the company has the skills to take the molecule into phase 2b. But the ultimate goal is to “find a very committed partner,” Steensberg said, that can put up the money it will take to realize Zealand’s vision of establishing petrelintide as a backbone weight-loss therapy.
“With the data at hand, we have also been very clear that we will have more, you can say, progressed discussions with some potential partners to see if we have a shared vision for the product, because, at least before we approach phase 3, we see a clear need to partner, to have somebody that can support us in global reach, somebody who can help with investments in manufacturing,” Steensberg said.
Novo has paired its amylin analog with the active ingredient in Ozempic and Wegovy to make CagriSema, pointing to the potential to use petrelintide in combination therapies.