Rezolute’s Ersodetug Meets Phase 3 Tumor Hyperinsulinism Endpoint Ahead of 2027 FDA Discussions

Key Points

• Preliminary results show 13 of 16 participants achieved at least a 50% reduction in their glucose infusion rate, exceeding the nine responders required for study success.
• Twelve participants discontinued intravenous glucose completely.
• Completed study results and formal statistical analysis are expected by mid-December 2026.
• The findings strengthen the tumor hyperinsulinism program, while the approval pathway in congenital hyperinsulinism remains uncertain following a separate Phase 3 failure.

Rezolute Inc. (NASDAQ: RZLT) said its Phase 3 upLIFT study of ersodetug in tumor hyperinsulinism met its primary efficacy endpoint, giving the company a positive clinical result ahead of planned FDA discussions in the first quarter of 2027. The announcement is based on a preliminary November 5 data evaluation, with some participants still undergoing pivotal treatment.

Shares rose approximately 10% to $4.27 in premarket trading Friday, compared with Thursday’s close of $3.87, according to the supplied market report.

Most Participants Reduced or Eliminated IV Glucose Dependence

The single-arm, open-label study enrolled 16 patients with uncontrolled hypoglycemia associated with tumors. Twelve had insulin-secreting malignant islet cell tumors, known as insulinomas, and four had non-islet cell tumors. Participants receive ersodetug at 9 mg/kg weekly for eight weeks alongside standard care, with an option to continue in a longer-term extension.

The primary endpoint measures how many patients achieve at least a 50% reduction from baseline in glucose infusion rate—a measure of their dependence on intravenous glucose to manage low blood sugar. At least nine responders were needed to meet the study’s statistical success threshold. Thirteen have responded so far, including 12 who stopped IV glucose entirely.

Three participants remain in the pivotal treatment period, including two who have not yet met the response criterion. Another participant previously discontinued treatment to enter home hospice care and died one week later from cancer progression. That participant is counted as a nonresponder.

Rezolute said ersodetug has been well tolerated in the study’s pivotal and extension phases, with no drug-related safety findings identified to date. Completed results, including the formal primary-endpoint analysis, are expected by mid-December.

Tumor Results Follow a Setback in Congenital Hyperinsulinism

The positive findings contrast with the separate Phase 3 congenital hyperinsulinism study, which missed its primary endpoint. In that trial, reductions in hypoglycemia events did not significantly separate from placebo, leaving uncertainty around the indication’s regulatory prospects.

Both programs target excessive insulin-receptor activation. Ersodetug is an investigational antibody designed to reduce that activation by insulin and related substances, including IGF-2, which some tumors produce. The tumor study therefore provides additional evidence supporting the drug’s biological approach, but it does not resolve the failed congenital study’s efficacy questions.fiercebiotech+1

According to Rezolute, the FDA has recommended a pre-submission meeting before a potential biologics license application for congenital hyperinsulinism. The company cautioned that there is no assurance the agency will consider the totality of evidence sufficient for approval.

Investor Takeaway

The upLIFT result gives Rezolute a stronger clinical foundation for pursuing approval in tumor hyperinsulinism. The reduction in IV glucose dependence is the central finding, although the study is small, has no concurrent control group and is not yet complete.

The next catalysts are the final results expected in December and FDA discussions planned for the first quarter of 2027. Management hopes to advance both indications into the approval process next year, but investors should distinguish the positive tumor study from the unresolved congenital program. Ersodetug remains investigational and has not received regulatory approval.