Every one of the 59 patients who completed the randomized, placebo-controlled phase of sunRIZE enrolled in the open-label extension — and 57 are still attending regular visits. That 100% rollover rate, in a rare pediatric disease trial spanning a dozen countries, is not a routine statistic. It is a signal about how desperate families and clinicians are for anything that works in congenital hyperinsulinism, and it sets up the central tension in ersodetug’s regulatory story: a drug that appears to work in practice but stumbled on the metric that was supposed to prove it.
The pre-specified secondary endpoint — percent time in hypoglycemia by CGM — did not reach statistical significance at the Week 24 evaluation window. That failure matters, but the picture that emerges from the expanded analyses is harder to dismiss. Across the full analysis set, ersodetug reduced daily time in hypoglycemia by more than 50%; in the per-protocol population the reduction ran 60–80%. Weekly hypoglycemia events fell 50–65% in the FAS and up to 80% in the PPS. Normoglycemia exposure — time with glucose between 70 and 180 mg/dL — increased 25–50%. These are not marginal signals scattered across post-hoc fishing; they are consistent in direction and magnitude across multiple pre-specified and post-hoc CGM endpoints, across time, and across both dose arms. The problem is the primary endpoint was finger-stick SMBG events, a coarser and more variable capture method in a population where caregivers are already hypervigilant. The FDA acknowledged as much at the March 2026 Type B meeting, conceding the challenges inherent in that endpoint design.
What emerged from that meeting is structurally unusual: the agency did not issue a refuse-to-file signal or a clear path to resubmission. It asked Rezolute to submit the full dataset for comprehensive evaluation before determining next steps. That is neither a green light nor a rejection — it is a deliberate deferral that preserves optionality for both sides. In the OLE, former placebo patients showed clinically significant glycemic improvements after crossing over, and a meaningful subset of participants have discontinued background standard-of-care therapies including diazoxide and somatostatin analogs entirely, receiving ersodetug as monotherapy. That shift in background therapy is a hard clinical outcome, not a surrogate.
The single marker to track is the FDA’s formal response after reviewing the complete submission — specifically whether the agency accepts CGM-based endpoints as the evidentiary foundation for approval or demands a new adequately powered trial built around a different primary measure. That decision will define not just ersodetug’s fate but the measurement standard for every future hyperinsulinism drug.
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.
