Every one of the 59 patients who completed the randomized phase of sunRIZE elected to enter the open-label extension — a 100% rollover rate that, in a blinded placebo-controlled rare disease trial, is not routine. That figure matters more than any single p-value from the controlled period, because it reflects how desperate families and clinicians are for anything that works in congenital hyperinsulinism, and it gives Rezolute a durable efficacy dataset at a moment when the primary endpoint result has left the regulatory path genuinely uncertain.
The core tension in the sunRIZE readout is that statistical significance on the pre-specified secondary endpoint — percent time in hypoglycemia by CGM at the Week 24 evaluation window — was not achieved, yet the directional signal is hard to dismiss. Across the full analysis set, ersodetug reduced daily time in hypoglycemia by more than 50%, cut weekly hypoglycemic events by roughly 50–65%, and increased time in normoglycemia by 25–50%, with most of these differences reaching nominal significance at multiple maintenance-phase timepoints outside the primary window. The problem is timing: the effect appears to build through the maintenance dosing period rather than crystallize neatly at the pre-specified evaluation point, which is exactly the kind of mismatch that makes a pivotal trial difficult to interpret and a standard approval pathway difficult to execute.
The FDA’s posture after the March Type B meeting is the most consequential element here. The agency explicitly acknowledged challenges with the finger-stick SMBG primary endpoint — the instrument that generated the topline miss — and asked Rezolute to submit the full data package for comprehensive review rather than issuing a clear rejection or a defined remediation path. That is neither a green light nor a closed door. It is a signal that the agency sees something worth examining in a dataset that conventional endpoint analysis obscured. The OLE data, particularly the reduction and outright discontinuation of background diazoxide and somatostatin analogs in a meaningful subset of patients now on ersodetug monotherapy, strengthens the biological coherence of the argument Rezolute will make in that submission.
The single marker to watch is whether FDA’s comprehensive data review produces a request for an additional study or accepts a rolling NDA built on the existing package with CGM-based endpoints repositioned as the primary evidence — that decision determines whether ersodetug reaches patients in two years or five.
Jon Napitupulu is Director of Media Relations at The Clinical Trial Vanguard. Jon, a computer data scientist, focuses on the latest clinical trial industry news and trends.
