Zealand Pharma’s GLP-1/GLP-2 receptor dual agonist may have only managed at best an average 4.3% reduction in weight loss when given in low doses, but the Danish company is keen to stress that higher doses are where the drug should prove its worth.
The 54-person phase 2 trial involved administering either 4-mg weekly subcutaneous doses of dapiglutide, a 6-mg dose or placebo over 12 weeks. Participants who received 4 mg saw an average weight loss of 2.9%, barely above the 2.2% seen in the placebo cohort. The 6-mg group saw a slightly larger weight loss of 4.3%. No lifestyle interventions were part of the trial.
Drilling down into the numbers, both missed statistical significance, with the lowest dose hitting a dismal p-value of p=0.483 while the higher dose hit p=0.077.
The results suggest that the 4-mg and 6-mg doses are at the “lower end of the therapeutic range,” Zealand observed.
Despite the unimpressive data, the biotech was keen to stress that “much higher doses of dapiglutide are being investigated in the ongoing 13-week phase 1b trial,” which is expected to read out its own top-line results in the second half of the year.
“We are encouraged by the reductions in body weight observed in this investigator-led mechanistic trial using low doses of dapiglutide,” Zealand Chief Medical Officer David Kendall, M.D., said in the May 23 release.
“Our ongoing 13-week phase 1b dose-titration trial is currently evaluating higher doses of dapiglutide up to 13 mg, and based on the tolerability profile observed to date, we will seek to investigate even higher doses going forward,” Kendall added. The company is now clearly betting that it can hit efficacy with the higher doses.
Investors were, however, clearly irked, sending the Danish pharma's shares in European trading down more than 3% in early morning trading CEST time.
The number of treatment-emergent adverse events, which tended to be gastrointestinal-related, were lower than have been reported from studies of other incretin-based therapies, the company said. None of these events led to patients discontinuing their treatment.
Regardless of yesterday’s results, the attention of investors appears to be elsewhere in Zealand’s pipeline. In a note last week, analysts at Jefferies described an upcoming phase 1b weight loss readout from the biotech’s long-acting amylin petrelintide as the company’s “most-watched catalyst.”
The analysts also homed in on Zealand's survodutide after the Boehringer Ingelheim-partnered glucagon/GLP-1 agonist demonstrated its potential to treat metabolic dysfunction-associated steatohepatitis in a phase 2 trial earlier this year. In contrast, dapiglutide only received a cursory mention in the analysts’ highlights.