Rezolute completes enrolment in Phase 3 upLIFT tumour HI study

Rezolute has completed enrolment in the upLIFT Phase 3 study of ersodetug, its monoclonal antibody candidate for tumour hyperinsulinism (HI), with topline results expected in mid-December 2026. The Redwood City-based company said it will also continue its expanded access programme, allowing compassionate use of ersodetug for patients with serious and refractory hypoglycaemia caused by tumour HI while the registrational data mature.

The single-arm, open-label trial enrolled 16 participants with insulinoma or non-islet cell tumours (NICTs) suffering from uncontrolled hypoglycaemia. Participants receive ersodetug at 9 mg/kg weekly for eight weeks as an add-on to standard of care. The primary endpoint requires that the lower bound of the 95% confidence interval for the responder rate sits at or above 30%, which equates to at least nine of 16 participants achieving a 50% or greater reduction from baseline in intravenous glucose infusion rate.

Interim signal and a notable safety event

Interim data from the first eight participants enrolled in upLIFT showed that seven met the primary responder criterion, and all seven achieved complete discontinuation of intravenous glucose. The eighth participant elected to pursue hospice care shortly after enrolment and died one week later due to cancer progression; the company is counting this individual as a non-responder in the primary analysis, consistent with standard registrational-trial methodology.

Ersodetug has been well-tolerated across the study thus far, with no drug-related safety findings reported. Chief medical officer Brian Roberts said that with a clear path forward now in place, the company looks forward to reporting topline data and, should the results be favourable, advancing both tumour HI and congenital HI programmes in 2027.

Market and regulatory context

Tumour hyperinsulinism is an ultra-rare condition affecting patients with insulinomas and a subset of non-islet cell malignancies, including hepatocellular carcinoma and soft-tissue sarcomas that secrete IGF-2-like paraneoplastic substances. There are currently no approved therapies specifically targeting HI at the insulin receptor level; management relies on intravenous dextrose infusion, dietary modification, and, where surgically feasible, tumour resection. The unmet need is acute: patients with unresectable tumours face persistent hypoglycaemia with high associated morbidity and mortality.

Ersodetug's mechanism, allosteric blockade of the insulin receptor downstream of insulin and IGF-2 secretion, is differentiated from somatostatin analogues such as octreotide, which reduce hormonal output rather than block receptor activation. This positions ersodetug as potentially effective across multiple HI aetiologies, a breadth Rezolute is pursuing across congenital HI and post-bariatric surgery hypoglycaemia in parallel programmes.

Ultra-rare registrational trials with small single-arm cohorts face a particular scrutiny from the FDA around historical control benchmarks and the robustness of confidence interval thresholds. The pre-specified 30% lower-bound CI was agreed with regulators as the statistical anchor for this study; the interim data pattern, seven of eight responders, implies that the final readout could comfortably exceed that bar if the second cohort performs comparably. Investors will, however, be watching the complete dataset closely, including secondary endpoints on time to hospital discharge and patient-reported quality of life, before drawing conclusions about the regulatory path to a new drug application.

Rezolute trades on NASDAQ under the ticker RZLT. The company has not disclosed current cash runway or a projected NDA filing timeline.