Zealand Pharma’s phase 3 short bowel syndrome (SBS) study has hit its primary endpoint, delivering data that could equip it to seek approval for a challenger to Takeda’s Gattex. But with the once-weekly dose failing to beat placebo and the data leaving scope to doubt whether Zealand’s glepaglutide represents a step up efficacy, questions about the commercial impact of the long-acting GLP-2 analog remain live.
Gattex, another GLP-2 analog, is already FDA-approved for the treatment of adults with SBS who are dependent on parenteral support for nutrition. However, the subcutaneous treatment is given every day, giving glepaglutide a potential convenience advantage over Takeda’s incumbent therapy even though only the twice-weekly dose hit the primary endpoint.
Glepaglutide may have a slight efficacy edge, too, although that is harder to judge given the available data and the limitations of cross-trial comparisons. At Week 24 of a trial that supported FDA approval, Gattex reduced (PDF) the mean weekly parenteral nutrition volume by 4.4 liters from a baseline of 12.9 liters, versus a 2.3-liter reduction in the placebo group.
Zealand tracked a 5.13-liter reduction in the twice-weekly arm of its 24-week glepaglutide clinical trial, compared to declines of 2.85 liters and 3.13 liters in, respectively, the placebo and once-weekly groups. The Zealand statement to disclose the results lacks the baseline figure for its trial.
Another endpoint paints glepaglutide in a less-favorable light. In the Gattex trial, 63% of the recipients of the drug experienced a 20% or greater reduction in weekly parenteral nutrition, versus 30% in the placebo group. The figures for the twice-weekly and control arms of the Zealand trial were 65.7% and 38.9%, respectively, resulting in a smaller placebo-adjusted response rate than in the Gattex trial.
Zealand’s push to show glepaglutide is a better drug than Gattex may be complicated by the anticipated arrival of generic copies of the Takeda drug in the U.S. But investors took the positives from the data and sent the stock up 26% on the exchange in the biotech’s native Denmark.
Having delivered the phase 3 data, Zealand is now working to generate results from a pair of long-term extension studies. Ninety-six of the 106 patients in the phase 3 moved into the long-term extensions. Zealand will now engage with regulatory authorities while planning its filing for approval in the U.S.