Ersodetug
An investigational treatment for Congenital Hyperinsulinism.
The same compound appears under different names depending on the context. Here is how to identify Ersodetug wherever you encounter it, plus the key facts at a glance.
- Generic name
- Ersodetug
- Development codes
- RZ358, XOMA 358, X358
- Drug class
- Insulin receptor antibody
- Manufacturer
- Rezolute
- How it's taken
- Infusion in a clinical trial; every 2 weeks at first, then every 4 weeks
Rezolute's antibody for congenital hyperinsulinism works downstream of the pancreas, blunting insulin's effect rather than its release. The Phase 3 sunRIZE trial missed its primary endpoint in December 2025, but after reviewing the full glucose-monitor data the FDA recommended a pre-BLA meeting in October 2026; no application has been filed.
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Where Ersodetug fits
Not available outside the sunRIZE extension. If approved, it would be the first HI treatment that acts on the insulin receptor rather than the pancreas, aimed at children and adults whose lows persist despite diazoxide, somatostatin analogs, feeds or surgery.
How Ersodetug works
Every other HI treatment tries to stop the pancreas from releasing insulin. Ersodetug lets the insulin be released and instead sits on the insulin receptor, the docking site on muscle, liver and fat cells, and turns its signal down. Because it acts after the pancreas, it could in principle help any form of hyperinsulinism regardless of the gene involved, including diffuse KATP disease and children who still have lows after a near-total pancreatectomy.
It is a large antibody, so it is given by infusion rather than by mouth; in the Phase 2 study it was infused into a vein every 2 weeks.
Mechanism: Fully human monoclonal antibody that binds the insulin receptor at a site away from insulin's and turns down receptor signaling, so excess insulin has less effect on the body
Side effects and safety
In the Phase 3 sunRIZE trial Rezolute described safety as generally favorable. Two participants had serious hypersensitivity (allergic) reactions and stopped the drug. The most common side effect seen more often than with placebo was hypertrichosis (extra body hair), which the company called generally mild and self-limiting. In the earlier Phase 2 RIZE study of 23 patients, the publication reported no adverse drug reactions, withdrawals or dose-limiting toxicities.
Because the drug lowers insulin's effect, high blood sugar is a theoretical risk that trials monitored.
This is not a complete list of side effects. Talk to your doctor or pharmacist about what to expect and when to seek medical attention.
Taking Ersodetug
Given as an infusion by weight. In sunRIZE, children and adults got 5 mg/kg or 10 mg/kg (or placebo) on top of their usual treatment every 2 weeks during a 6-week loading period and then every 4 weeks for the rest of the 24-week trial, followed by an optional open-label extension. Rezolute's sunRIZE releases do not state the route; the Phase 2 publication describes intravenous infusion. The drug is only available inside clinical studies.
Availability and cost
Only available as the brand-name product.
An investigational monoclonal antibody for an ultra-rare disease with Breakthrough Therapy and Orphan designations; if approved it would be priced as a specialty biologic. No price exists today.
How congenital hyperinsulinism treatments compare
Diazoxide (Proglycem) is the only medicine the FDA has approved for hyperinsulinism. Octreotide is the usual next step but is used off-label, and the 2 investigational drugs shown are not approved for anyone outside a trial. Your HI team chooses based on the gene result, whether diazoxide works, and whether a focal lesion can be removed by surgery.
Congenital Hyperinsulinism has 1 FDA-approved treatment: Proglycem (and generics) (diazoxide, approved 1976). Also compared, not FDA-approved for congenital hyperinsulinism: Sandostatin (off-label) (octreotide, Off-label (approved 1988 for acromegaly)); Ersodetug (investigational) (ersodetug (RZ358), Phase 3 missed primary endpoint (Dec 2025); FDA recommended a pre-BLA meeting (Oct 2026)); Dasiglucagon pump (investigational) (dasiglucagon, Complete Response Letters Dec 2023 and Oct 2024; resubmission expected H2 2026). Proglycem (and generics) is typically used as first-line for every confirmed diagnosis; works in roughly half of children, mostly those without 2 recessive katp gene changes.
| Drug | How it works | How it’s given | How often | Where you get it | Typical use | FDA status |
|---|---|---|---|---|---|---|
Proglycem (and generics) diazoxide | KATP channel opener: props open the beta cell's potassium gate so it cannot fire and release insulin | Oral suspension by dropper or syringe | Twice or 3 times a day | Home, after a hospital start with close glucose checks | First-line for every confirmed diagnosis; works in roughly half of children, mostly those without 2 recessive KATP gene changes | 1976 |
Sandostatin (off-label) octreotide | Somatostatin analog: dampens insulin release even when the KATP gate is broken | Injection under the skin or continuous pump; monthly octreotide LAR or lanreotide once stable | Several times a day or continuous; monthly for long-acting forms | Home injections or pump after hospital training; clinic for monthly depot shots | Second-line when diazoxide fails or is not tolerated, usually with feeds, while focal versus diffuse disease is sorted out | Off-label (approved 1988 for acromegaly) |
Ersodetug (investigational) ersodetug (RZ358) You are here | Insulin receptor antibody: lets insulin be released but blocks its effect on the body's cells | Infusion (intravenous in the Phase 2 study) | Every 2 weeks at first, then every 4 weeks in the Phase 3 trial | Trial sites only | Studied as an add-on for children and adults with lows despite standard care; could work regardless of gene | Phase 3 missed primary endpoint (Dec 2025); FDA recommended a pre-BLA meeting (Oct 2026) |
Dasiglucagon pump (investigational) dasiglucagon | Stable glucagon analog: tells the liver to release stored sugar to offset the extra insulin | Continuous infusion under the skin from a wearable pump | Around the clock | Trial sites only; designed for hospital start then home | Studied to cut IV dextrose in newborns and to reduce lows in children not controlled by medicines or surgery | Complete Response Letters Dec 2023 and Oct 2024; resubmission expected H2 2026 |
This chart is for understanding, not medical advice. Only diazoxide is FDA-approved for hyperinsulinism; octreotide is prescribed off-label by HI specialists, and ersodetug and dasiglucagon are investigational and available only in clinical studies. Feeds, IV dextrose, emergency glucagon and surgery are also central to HI care and are not shown here. Always discuss options with a hyperinsulinism center.
Clinical trial results
Phase 2 RIZE (NCT04538989, published in Med in 2025): 23 patients age 2 and older on standard care added ersodetug 3 mg/kg to 9 mg/kg every 2 weeks for 8 weeks; median reductions of 59% in hypoglycemia events by finger-stick and 54% in time in hypoglycemia by CGM. Phase 3 sunRIZE (NCT06208215): 63 participants age 3 months to 45 years in 13 countries, randomized 2 to 1 to 5 mg/kg, 10 mg/kg or placebo as add-on for 24 weeks, plus an open-label infant arm.
On December 11, 2025 Rezolute reported the trial did not meet its primary endpoint: hypoglycemia events by self-monitored blood glucose fell about 45% at 10 mg/kg against about 40% on placebo, not a significant difference, and the key secondary endpoint, time in hypoglycemia by CGM at week 24, was also missed (about 25% lower at 10 mg/kg against about 5% higher on placebo).
Rezolute later reported that the CGM difference was significant at week 16 but not at week 24, and presented post hoc CGM analyses in May 2026. Of 59 completers, all entered the extension and 57 remained in January 2026.
Development history
The antibody began as XOMA 358, with a first-in-human study published in 2017, and was licensed to Rezolute as RZ358; the INN ersodetug appeared in company releases from mid-2024. The FDA lifted partial clinical holds in September 2024, clearing US sites to join sunRIZE at all doses and down to age 3 months, and granted Breakthrough Therapy Designation for congenital HI on January 7, 2025.
Enrollment finished in May 2025. After the December 2025 miss, Rezolute held a Type B meeting with the FDA on March 17, 2026, at which the agency acknowledged the behavioral factors and finger-stick limitations in this population but reiterated its expectation of adequate and well-controlled studies, and asked for the CGM datasets.
Rezolute submitted them in June 2026. On October 5, 2026 the company announced that, after a preliminary review, the FDA recommended a Type B pre-BLA meeting as a precursor to a BLA for congenital HI, while stating that it had not opined on approvability and that a new randomized trial could still be required. Rezolute said it would set its BLA strategy after topline results from its tumor hyperinsulinism trial, upLIFT, expected in mid-December 2026. No pre-BLA meeting date or BLA filing has been disclosed.
Explore Congenital Hyperinsulinism trials
Other Congenital Hyperinsulinism treatments
Where to access Ersodetug
Investigational: available only through clinical trial enrollment
Ersodetug has not been approved by the FDA and is not available by prescription. The only way for a patient to receive Ersodetug today is by enrolling in an active clinical trial and meeting that trial's eligibility criteria. Decisions about trial participation should be made with the specialist who manages the patient's condition and knows their current treatment.
Primary active trial
ClinicalTrials.gov record NCT06208215
View full trial record on ClinicalTrials.gov →Trial status, site list, and eligibility are pulled from ClinicalTrials.gov. Confirm current recruitment status and nearest site directly with the study team before traveling.
Common questions about Ersodetug
▸What is Ersodetug?
Rezolute's antibody for congenital hyperinsulinism works downstream of the pancreas, blunting insulin's effect rather than its release. The Phase 3 sunRIZE trial missed its primary endpoint in December 2025, but after reviewing the full glucose-monitor data the FDA recommended a pre-BLA meeting in October 2026; no application has been filed.
▸How does Ersodetug work?
Every other HI treatment tries to stop the pancreas from releasing insulin. Ersodetug lets the insulin be released and instead sits on the insulin receptor, the docking site on muscle, liver and fat cells, and turns its signal down. Because it acts after the pancreas, it could in principle help any form of hyperinsulinism regardless of the gene involved, including diffuse KATP disease and children who still have lows after a near-total pancreatectomy. It is a large antibody, so it is given by infusion rather than by mouth; in the Phase 2 study it was infused into a vein every 2 weeks.
▸What are the side effects of Ersodetug?
In the Phase 3 sunRIZE trial Rezolute described safety as generally favorable. Two participants had serious hypersensitivity (allergic) reactions and stopped the drug. The most common side effect seen more often than with placebo was hypertrichosis (extra body hair), which the company called generally mild and self-limiting. In the earlier Phase 2 RIZE study of 23 patients, the publication reported no adverse drug reactions, withdrawals or dose-limiting toxicities. Because the drug lowers insulin's effect, high blood sugar is a theoretical risk that trials monitored.
▸How is Ersodetug taken?
Given as an infusion by weight. In sunRIZE, children and adults got 5 mg/kg or 10 mg/kg (or placebo) on top of their usual treatment every 2 weeks during a 6-week loading period and then every 4 weeks for the rest of the 24-week trial, followed by an optional open-label extension. Rezolute's sunRIZE releases do not state the route; the Phase 2 publication describes intravenous infusion. The drug is only available inside clinical studies.
▸Is Ersodetug FDA approved?
Ersodetug is currently in trial failed clinical trials for Congenital Hyperinsulinism. It has not yet received FDA approval.
▸Did ersodetug fail its Phase 3 trial?
The sunRIZE trial did not meet its primary endpoint. Rezolute reported on December 11, 2025 that hypoglycemia events by finger-stick fell about 45% at the 10 mg/kg dose against about 40% on placebo, which was not statistically significant, and the key secondary CGM endpoint at week 24 was also missed. The company attributes the result partly to a large placebo response.
▸Is ersodetug going to be submitted to the FDA?
Not yet. On October 5, 2026 Rezolute said the FDA, after reviewing the full CGM datasets, recommended a pre-BLA meeting as a precursor to a BLA for congenital HI, while saying plainly it had not decided on approvability and might still require a new randomized trial. Rezolute will decide its filing strategy after its tumor HI trial reads out in mid-December 2026.
▸Can my child get ersodetug now?
Only participants already in the sunRIZE open-label extension receive it. Rezolute has not announced an expanded access program for congenital HI; its only expanded access program is for tumor hyperinsulinism.
▸How is ersodetug different from diazoxide and octreotide?
Diazoxide and octreotide try to stop the pancreas from releasing insulin. Ersodetug is an antibody that blocks the insulin receptor on the body's cells, so the insulin that is released has less effect. That means it could work regardless of which gene causes the disease.
Sources and references
Every factual claim on this page is drawn from the public sources listed below. Click any reference to open the original document.
- Rezolute investor relations · 2025-12-11. Rezolute Announces Topline Results from the Phase 3 sunRIZE Study of Ersodetug in Congenital Hyperinsulinism. https://ir.rezolutebio.com/news/detail/368/
- Rezolute investor relations · 2026-03-24. Rezolute Provides Update Following Type B Meeting with FDA on Ersodetug for Congenital Hyperinsulinism. https://ir.rezolutebio.com/news/detail/373/
- Rezolute investor relations · 2026-10-05. Rezolute Announces FDA Recommendation to Hold a Pre-BLA Meeting as a Precursor to Submitting a Biologics License Application (BLA) for Congenital Hyperinsulinism. https://ir.rezolutebio.com/news/detail/385/
- Rezolute investor relations · 2026-10-14. Rezolute Announces Completion of Enrollment in the Phase 3 upLIFT Study of Ersodetug in Tumor Hyperinsulinism. https://ir.rezolutebio.com/news/detail/386/
- Rezolute investor relations · 2025-01-07. Rezolute Receives FDA Breakthrough Therapy Designation for Ersodetug in Congenital Hyperinsulinism. https://ir.rezolutebio.com/news/detail/345/
- Rezolute investor relations · 2023-12-14. Rezolute Announces Initiation of Phase 3 sunRIZE Study. https://ir.rezolutebio.com/news/detail/323/
- Med (Cell Press), PubMed 40107271 · 2025. Phase 2b RIZE study of ersodetug (RZ358) in congenital hyperinsulinism. https://pubmed.ncbi.nlm.nih.gov/40107271/
- ClinicalTrials.gov. RZ358 Treatment for Congenital Hyperinsulinism (sunRIZE). https://clinicaltrials.gov/study/NCT06208215