Rezolute Announces Alignment with FDA on Streamlined Design for Ongoing Phase 3 Trial of Ersodetug in Tumor Hyperinsulinism
Rezolute (NASDAQ:RZLT) has secured FDA alignment for a streamlined Phase 3 trial design of ersodetug in tumor hyperinsulinism (HI). The agency approved significant modifications to the upLIFT study, eliminating the need for a double-blind placebo-controlled trial and reducing the required participants to as few as 16 patients.
The study will now proceed as a single-arm open-label trial, with patient recruitment ongoing in the U.S. and Europe. The FDA will consider Rezolute's pivotal sunRIZE trial in congenital HI as confirmatory evidence, acknowledging ersodetug's broader applicability. Topline data is expected in the second half of 2026, while the sunRIZE trial results are anticipated in December 2025.
Rezolute (NASDAQ:RZLT) ha ottenuto l’allineamento della FDA per un disegno di fase 3 semplificato di ersodetug nel trattamento dell’iperinsulinemia tumorale (HI). L’agenzia ha approvato modifiche sostanziali allo studio upLIFT, eliminando la necessità di un trial controllato in cieco con placebo e riducendo il numero di partecipanti necessari fino a 16 pazienti.
Lo studio proseguirà come trial monocentrico a braccio singolo e in aperto, con reclutamento di pazienti in corso negli USA e in Europa. La FDA considererà lo studio pivotal sunRIZE sulla HI congenita come prova confermativa, riconoscendo la più ampia applicabilità di ersodetug. I dati topline sono attesi nella seconda metà del 2026, mentre i risultati di sunRIZE sono previsti per dicembre 2025.
Rezolute (NASDAQ:RZLT) logró el respaldo de la FDA para un diseño de fase 3 simplificado de ersodetug en hiperinsulinemia tumoral (HI). La agencia aprobó cambios importantes en el estudio upLIFT, suprimiendo la exigencia de un ensayo aleatorizado doble ciego con placebo y reduciendo el número de participantes necesarios hasta 16 pacientes.
El estudio seguirá como un ensayo abierto de un solo brazo, con reclutamiento de pacientes en curso en EE. UU. y Europa. La FDA aceptará el ensayo pivotal sunRIZE en HI congénita como evidencia confirmatoria, reconociendo la aplicabilidad más amplia de ersodetug. Se esperan los datos topline en la segunda mitad de 2026, mientras que los resultados de sunRIZE se anticipan para diciembre de 2025.
Rezolute (NASDAQ:RZLT)가 종양성 고인슐린혈증(HI) 치료제 ersodetug의 간소화된 3상 설계에 대해 FDA의 합의를 얻었습니다. 규제 당국은 upLIFT 시험에 대한 주요 변경을 승인하여 이중맹검 위약대조 시험의 필요성을 없애고 필요한 참여자 수를 16명까지 줄였습니다.
해당 연구는 단일군 공개(label-open) 시험으로 진행되며 미국과 유럽에서 환자 모집이 진행 중입니다. FDA는 선천성 HI에 대한 Rezolute의 결정적(pivotal) sunRIZE 시험을 확인용 증거로 인정하여 ersodetug의 광범위한 적용 가능성을 인정했습니다. 톱라인 데이터는 2026년 하반기에 기대되며, sunRIZE 시험 결과는 2025년 12월로 예정되어 있습니다.
Rezolute (NASDAQ:RZLT) a obtenu l’alignement de la FDA pour un dessin d’essai de phase 3 simplifié d’ersodetug dans l’hyperinsulinisme tumoral (HI). L’agence a approuvé des modifications majeures de l’étude upLIFT, supprimant la nécessité d’un essai contrôlé en double aveugle avec placebo et réduisant le nombre de participants requis à seulement 16 patients.
L’étude se déroulera désormais en essai ouvert à bras unique, avec un recrutement de patients en cours aux États‑Unis et en Europe. La FDA considérera l’essai pivot sunRIZE de Rezolute en HI congénitale comme preuve confirmatoire, reconnaissant l’applicabilité plus large d’ersodetug. Les résultats topline sont attendus dans la seconde moitié de 2026, tandis que les résultats de sunRIZE sont prévus pour décembre 2025.
Rezolute (NASDAQ:RZLT) hat von der FDA eine Übereinkunft für ein vereinfachtes Phase‑3‑Studiendesign von ersodetug bei tumorbedingter Hyperinsulinämie (HI) erhalten. Die Behörde genehmigte wesentliche Änderungen am upLIFT‑Studieprotokoll, hob die Notwendigkeit einer doppelblinden Placebo‑kontrollierten Studie auf und verringerte die erforderliche Teilnehmerzahl auf lediglich 16 Patienten.
Die Studie wird nun als offener, einarmiger Versuch durchgeführt, mit laufender Patientenrekrutierung in den USA und Europa. Die FDA wird Rezolutes entscheidende sunRIZE‑Studie bei angeborener HI als bestätigende Evidenz anerkennen und damit die breitere Anwendbarkeit von ersodetug würdigen. Die Topline‑Daten werden für die zweite Hälfte 2026 erwartet, die sunRIZE‑Ergebnisse für Dezember 2025.
- FDA agreement to significantly streamline Phase 3 trial design
- Reduction in required patient enrollment from original design to just 16 participants
- Elimination of placebo-controlled requirement, potentially accelerating trial completion
- Favorable outcomes observed in over 10 patients under Expanded Access Program
- FDA acceptance of sunRIZE trial as confirmatory evidence
- None.
Insights
FDA streamlining Rezolute's tumor HI trial is a significant regulatory win, accelerating approval timeline and reducing costs substantially.
The FDA's agreement to simplify Rezolute's Phase 3 upLIFT trial for ersodetug represents a major regulatory victory that substantially improves the company's clinical development outlook. The modification from a double-blind, placebo-controlled design to a single-arm open-label study with as few as 16 patients is extraordinary in Phase 3 development and will dramatically reduce both time and costs.
This streamlined approach has several critical implications. First, the acceptance of the congenital HI pivotal trial (sunRIZE) as confirmatory evidence demonstrates the FDA's confidence in ersodetug's mechanism across multiple forms of hyperinsulinism. Second, the real-world evidence from treating over 10 expanded access patients likely provided compelling efficacy signals that supported this decision.
From a development perspective, this significantly de-risks the program. Patient recruitment—often the most challenging aspect of rare disease trials—becomes far more manageable with the smaller sample size and open-label design. The expected topline data in H2 2026 now has a much higher probability of being delivered on schedule.
This regulatory flexibility aligns with the FDA's recent emphasis on accelerating therapies for rare diseases with high unmet needs. The agency's willingness to accept alternative trial designs and leverage data across related indications suggests they recognize the therapeutic potential of ersodetug and the urgent need among tumor HI patients who currently have limited treatment options.
Open-label study in as few as 16 tumor hyperinsulinism (HI) patients
Study initiated and enrolling patients in the U.S. and Europe
Topline data expected in the second half of 2026
REDWOOD CITY, Calif., Sept. 02, 2025 (GLOBE NEWSWIRE) -- Rezolute, Inc. (Nasdaq: RZLT) (“Rezolute” or the “Company”), a late-stage rare disease company focused on treating hypoglycemia caused by hyperinsulinism, today announced that the Company has gained alignment with FDA on a significantly streamlined clinical development path for its ongoing Phase 3 study (upLIFT) of ersodetug for the treatment of hypoglycemia caused by tumor HI.
At a meeting held with FDA on August 19, 2025, the agency agreed to modifications to the design of the study including removing the need to conduct a double-blind randomized placebo-controlled trial. The truncated study will include as few as 16 participants and will be limited to the single-arm open-label portion of the upLIFT study, which has been the focus of the Company’s patient recruitment efforts. FDA also confirmed that Rezolute’s pivotal sunRIZE trial in congenital HI, which is on track to report topline results in December 2025, would serve as confirmatory clinical evidence, and is demonstrative of FDA’s recognition of the broad applicability of ersodetug in multiple forms of HI.
“We are absolutely delighted with this regulatory outcome,” said Nevan Charles Elam, Chief Executive Officer and Founder of Rezolute. “The FDA’s staff and leadership have been very vocal about the desire to responsibly simplify clinical development for rare diseases, particularly when there is real-world evidence of benefit combined with mechanistic plausibility. We believe that the alignment we have achieved with the agency exemplifies this innovative approach and is substantially based upon the favorable outcomes that we have observed over the last two years treating more than 10 patients with tumor HI under our Expanded Access Program.”
Brian Roberts, M.D., Chief Medical Officer at Rezolute went on to say, “This revised and simplified plan for the upLIFT study and approval pathway marks an important development for us as well as the community of healthcare providers, patients, and families living with serious hypoglycemia caused by tumor HI. By focusing on an open-label study in upLIFT, while building upon the robust clinical foundation established in the congenital HI indication, we are expediting development with the goal of making this therapy available as efficiently as possible.”
About upLIFT
The Phase 3 registrational study is a single-arm, open-label, pivotal trial in approximately 16 participants with insulinoma or non-islet cell tumors who have uncontrolled hypoglycemia caused by tumor hyperinsulinism (HI). Eligible participants requiring continuous intravenous (IV) glucose will receive ersodetug 9 mg/kg per week for 8 weeks, as an add-on to standard of care. Following this 8-week pivotal treatment period, all participants may receive ersodetug in long-term extension. The primary endpoint is the number of participants achieving at least a 50 percent reduction from baseline in IV glucose requirements (glucose infusion rate; GIR). Additional endpoints include the number of participants and time to discontinuation of GIR, time to discharge from the hospital, extent of hypoglycemia events and hypoglycemia time in the outpatient setting by self-monitored blood glucose and continuous glucose monitor, respectively, and patient reported quality of life.
About Tumor Hyperinsulinism
Tumor hyperinsulinism (HI) is a rare disease that may be caused by two distinct types of tumors: islet cell tumors (ICTs) and non-islet cell tumors (NICTs), both of which lead to hypoglycemia as a result of over-activation of the insulin receptor. Insulinomas are the most common type of ICT and cause hypoglycemia by stimulating the over production of insulin. A variety of different NICTs, particularly hepatocellular carcinoma, can cause hypoglycemia by producing and secreting insulin-like paraneoplastic substances such as IGF-2 that bind to and activate the insulin receptor. With high morbidity and mortality rates within tumor HI, there remains a significant unmet need for new therapies directed at hypoglycemia treatment. Ersodetug has shown real-world benefit in patients with insulinoma and NICTs.
About Ersodetug
Ersodetug is a fully human monoclonal antibody that binds allosterically to the insulin receptor to decrease receptor over-activation by insulin and related substances (such as IGF-2) in the setting of hyperinsulinism (HI), thereby improving hypoglycemia. Because ersodetug acts downstream from the pancreas, it has the potential to be universally effective at treating hypoglycemia due to any congenital or acquired form of HI.
About Rezolute, Inc.
Rezolute is a late-stage rare disease company focused on treating hypoglycemia caused by hyperinsulinism (HI). The Company’s antibody therapy, ersodetug, is designed to treat all forms of HI and has shown meaningful benefit in clinical trials and real-world use for the treatment of both congenital and tumor HI. For more information, visit www.rezolutebio.com.
Forward-Looking Statements
This release, like many written and oral communications presented by Rezolute and our authorized officers, may contain certain forward-looking statements regarding our prospective performance and strategies within the meaning of Section 27A of the Securities Act and Section 21E of the Securities Exchange Act of 1934, as amended. We intend such forward-looking statements to be covered by the safe harbor provisions for forward-looking statements contained in the Private Securities Litigation Reform Act of 1995 and are including this statement for purposes of said safe harbor provisions. Forward-looking statements, which are based on certain assumptions and describe future plans, strategies, and expectations of Rezolute, are generally identified by use of words such as "anticipate," "believe," "estimate," "expect," "intend," "plan," "project," "seek," "strive," "try," or future or conditional verbs such as "could," "may," "should," "will," "would," or similar expressions. These forward-looking statements include, but are not limited to, statements regarding the potential efficacy of ersodetug in the congenital HI and tumor HI patient populations, the timeline for achieving results in the upLIFT studies and the potential approval and commercialization of ersodetug. Our ability to predict results or the actual effects of our plans or strategies is inherently uncertain. Accordingly, actual results may differ materially from anticipated results. Readers are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date of this release. Except as required by applicable law or regulation, Rezolute undertakes no obligation to update these forward-looking statements to reflect events or circumstances that occur after the date on which such statements were made. Important factors that may cause such a difference include any other factors discussed in our filings with the SEC, including the Risk Factors contained in the Rezolute’s Annual Report on Form 10-K and Quarterly Reports on Form 10-Q, which are available at the SEC’s website at www.sec.gov. You are urged to consider these factors carefully in evaluating the forward-looking statements in this release and are cautioned not to place undue reliance on such forward-looking statements, which are qualified in their entirety by this cautionary statement.
Contacts:
Rezolute, Inc.
Christen Baglaneas
cbaglaneas@rezolutebio.com
508-272-6717
FAQ
What changes did the FDA approve for Rezolute's Phase 3 trial of ersodetug?
When will Rezolute (RZLT) report topline data for the Phase 3 upLIFT trial?
What is the status of Rezolute's sunRIZE trial for congenital HI?
How many patients has Rezolute treated with ersodetug under their Expanded Access Program?
Where is Rezolute currently enrolling patients for the upLIFT study?
