Rezolute’s stock has plunged 87% after the company’s rare disease drug flunked the final clinical test ahead of a planned approval application.
The company had been evaluating ersodetug as a treatment for hypoglycemia in a phase 3 study of 63 patients aged between 3 months and 45 years around the world with congenital hyperinsulinism (HI). The biotech was confident enough in the study’s prospects that it recruited a chief commercial officer back in August to prepare for the commercialization of ersodetug.
But those plans have been thrown into doubt this morning as Rezolute revealed the trial missed its primary endpoint of a change in average weekly hypoglycemia events. The 45% reduction in self-monitored events among the highest, 10-mg/kg, ersodetug dose cohort was not statistically significant when compared to the 40% improvement seen in the placebo group, Rezolute explained in a Dec. 11 release.
There wasn’t a silver lining to be found in the study’s secondary endpoint, either, with the 25% reduction in time patients experienced hypoglycemia over six months among the 10-mg/kg ersodetug group not being deemed statistically significant when compared to a 5% increase in time across the placebo cohort.
Two patients experienced serious hypersensitivity reactions that led to early discontinuation of study drug, although the company claimed “incidence of serious allergic reactions across the program is relatively low compared to biologic or monoclonal antibody treatments.”
Investors took fright at the trial results, driving the company’s stock down 87% to $1.40 in early morning trading Thursday, falling from a Wednesday closing price of $10.94.
With a phase 3 study of ersodetug in tumor HI ongoing, Rezolute isn’t ready to write off the drug quite yet. The company’s chief medical officer Brian Roberts, M.D., said the biotech plans to meet with the FDA “to consider next steps for the program.”
“We are disappointed that the study did not demonstrate significant improvements in glucose-related endpoints relative to placebo as well as for the patients and families living with congenital HI who urgently need new treatment options,” Roberts said in this morning’s release.
“At the same time, there are aspects of the results that merit additional investigation, and we are conducting a thorough evaluation to gain a better understanding of the study outcomes, which will inform our path forward,” he added.
Patients with hypoglycemia caused by HI currently have limited options. Diazoxide is approved in the indication, but, with response rates ranging from 40% to 74%, there is room to improve on the treatment. Zealand Pharma has been preparing to refile for approval of dasiglucagon, a glucagon analog that it already sells as Zegalogue in other settings, in congenital HI after suffering two rejections in recent years.
Rezolute sees barriers to the use of dasiglucagon in congenital HI, though, telling (PDF) investors back in May that the utility in chronic use is unproven and predicting Zealand is likely to need to combine the drug with other therapies.
Rezolute’s ersodetug is a monoclonal antibody that binds to the insulin receptor to decrease over-activation by insulin and related substances. Because ersodetug acts downstream from the pancreas, Rezolute had been hoping the drug could be “universally effective at treating hypoglycemia due to any congenital or acquired form of hyperinsulinism.”
Hopes for the drug were raised back in 2022 when a phase 2 trial tied ersodetug to a 75% reduction in severe low blood sugar events in children, leading the company to raise $130 million to support a push into phase 3.
Only last month, Rezolute was explaining to investors that the company had secured alignment with the FDA on the registrational requirements for submitting an approval application for the therapy.