Rezolute Announces FDA Clearance of IND Application for Phase 3 Registrational Study of RZ358 for Treatment of Hypoglycemia Due to Tumor Hyperinsulinism

Rhea-AI Summary

Rezolute (Nasdaq: RZLT) has received FDA clearance for its IND application for RZ358 (ersodetug) to treat hypoglycemia in patients with tumor hyperinsulinism (HI). This marks the company's second rare disease program with RZ358 in Phase 3 development. The study will primarily be conducted in the U.S., with patient enrollment planned for the first half of 2025.

The Phase 3 registrational study is a double-blind, randomized, placebo-controlled trial involving 24 participants with inadequately controlled hypoglycemia due to tumor HI. The primary endpoint is the change in Level 2 and Level 3 hypoglycemia events. Ersodetug is a fully human monoclonal antibody that binds to an allosteric site on the insulin receptor, potentially offering a universal treatment for hypoglycemia caused by all forms of HI.

Positive

• FDA clearance for IND application of RZ358 (ersodetug) for tumor hyperinsulinism
• Second rare disease program with RZ358 in Phase 3 development
• Potential universal treatment for hypoglycemia caused by all forms of HI
• Positive real-world benefits observed in tumor HI patients through Expanded Access Program

Negative

• Patient enrollment for the new Phase 3 study not starting until first half of 2025
• Topline data from ongoing Phase 3 trial in congenital HI not expected until mid-2025

Medical Research Analyst

The FDA clearance for Rezolute's IND application for RZ358 (ersodetug) to treat hypoglycemia in tumor hyperinsulinism (HI) patients is a significant milestone. This marks the second rare disease program with RZ358 in Phase 3 development, following its ongoing study in congenital HI. The dual-pronged approach could potentially position ersodetug as a universal treatment for hypoglycemia caused by various forms of HI.

The planned Phase 3 study design is robust, with a randomized, placebo-controlled trial and an additional open-label arm for severely affected patients. The primary endpoint focusing on moderate and severe hypoglycemic events is clinically relevant. The inclusion of quality of life measures and hospitalization rates as secondary endpoints adds value to the potential real-world impact of the treatment.

Investors should note the projected timeline, with patient enrollment planned for H1 2025 and topline data from the congenital HI study expected in mid-2025. These milestones could serve as potential catalysts for the stock in the coming years.

Financial Analyst

Rezolute's advancement of RZ358 into Phase 3 for tumor hyperinsulinism represents a significant expansion of its late-stage pipeline. This development could potentially increase the drug's market opportunity and diversify risk across multiple indications. The company's focus on rare diseases with high unmet needs aligns with a strategy that often leads to premium pricing and favorable reimbursement upon approval.

Investors should consider the financial implications of running two concurrent Phase 3 trials. While this demonstrates confidence in the drug's potential, it may also increase cash burn in the near term. The company's ability to fund these trials through completion will be crucial.

The market potential for a universal treatment for hypoglycemia in HI could be substantial, given the lack of approved therapies. However, the rarity of the conditions means that commercial success will depend on effective patient identification and market penetration strategies.

Oncology Expert

The development of ersodetug for tumor hyperinsulinism addresses a critical unmet need in oncology. Hypoglycemia in these patients can be life-threatening and often hinders cancer treatment. The potential for ersodetug to enable tumor-directed therapies by managing hypoglycemia is particularly noteworthy.

The mechanism of action of ersodetug, binding to an allosteric site on the insulin receptor, is innovative and could offer advantages over current management strategies. Its potential as a universal treatment for various forms of HI is promising.

The positive experiences from the Expanded Access Program provide encouraging real-world evidence. However, the small sample size of the planned Phase 3 trial (24 participants) may limit the statistical power. The inclusion of an open-label arm for severely affected patients is a thoughtful addition that could provide valuable data on the most challenging cases.

Second rare disease program with RZ358 in Phase 3 development

Follows successful treatment of multiple patients with tumor hyperinsulinism
under the Company’s Expanded Access Program

REDWOOD CITY, Calif., Aug. 05, 2024 (GLOBE NEWSWIRE) -- Rezolute, Inc. (Nasdaq: RZLT) (“Rezolute” or the “Company”), a late-stage biopharmaceutical company committed to developing novel, transformative therapies for serious rare diseases, today announced that it received U.S. Food and Drug Administration (FDA) clearance for its Investigational New Drug (IND) application for RZ358 (ersodetug) to treat hypoglycemia in patients with tumor hyperinsulinism (HI). The Company is initiating start-up activities for the study which will be primarily conducted in the U.S. and patient enrollment is planned to commence in the first half of 2025. Ersodetug is also being studied in an ongoing global, pivotal, Phase 3 clinical trial in patients with congenital HI. Topline data from that study is expected in mid-2025.

“Hypoglycemia associated with tumor HI requires treatment to prevent serious adverse outcomes and to improve patients’ daily function and quality of life, including enabling them to receive tumor directed therapies,” said Brian Roberts, M.D., Chief Medical Officer at Rezolute. “We are encouraged by the substantial real-world benefit we’ve witnessed in tumor HI patients who have previously received ersodetug in our Expanded Access Program, coupled with the safety and efficacy demonstrated in clinical studies in patients with congenital HI, a similar condition. We believe that the clearance of our IND for this Phase 3 study reflects FDA’s recognition of the potential for ersodetug to address this serious unmet need and we are excited to be moving one step closer to a potential universal treatment for hypoglycemia caused by all forms of HI.”

The Phase 3 registrational study is a double-blind, randomized, placebo-controlled trial of 24 participants who have inadequately controlled hypoglycemia because of tumor HI. Eligible participants will be randomized in 1:1 fashion (12 per treatment arm) to receive ersodetug 9 mg/kg per week or matched placebo, as an add-on to standard of care. Up to 24 additional participants may be enrolled into an open-label arm, in participants whose hypoglycemia is being managed by IV glucose in a hospital setting. Following a 6-week pivotal treatment period, all participants may receive ersodetug in open-label extension. The primary endpoint is the change in Level 2 (moderate) and Level 3 (severe) hypoglycemia events by self-monitored blood glucose. Additional endpoints include overall hypoglycemia events, time in hypoglycemia by continuous glucose monitor, patient reported quality of life, hospitalizations, and change in glucose requirements (for open-label hospitalized participants).

Ersodetug is a fully human monoclonal antibody that binds to an allosteric site on the insulin receptor at target tissues such as liver, fat and muscle. Ersodetug counteracts excess insulin receptor activation caused by insulin and related hormones thereby correcting hypoglycemia. Ersodetug has the potential to be universally effective at treating hypoglycemia caused by any form of HI, including congenital or acquired forms.

About Tumor Hyperinsulinism (HI)

Tumor 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 excessive activation of the insulin receptor. Insulinomas are the most common type of ICT and may 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 preclinical studies have shown that ersodetug can similarly blunt IGF-2 and insulin-mediated insulin-receptor signaling.

About Rezolute, Inc.

Rezolute is a late-stage rare disease company focused on significantly improving outcomes for individuals with hypoglycemia caused by HI. The Company’s antibody therapy, ersodetug, is designed to treat all forms of HI and has shown substantial benefit in clinical trials and real-world use for the treatment of congenital HI and tumor HI.

Forward-Looking Statements

Any statements in this press release about the Company’s future expectations, plans and prospects, including statements regarding the public offering, constitute forward-looking statements for purposes of the safe harbor provisions under the Private Securities Litigation Reform Act of 1995. Forward-looking statements include any statements about the Company’s strategy, future operations and future expectations and plans and prospects for the Company, and any other statements containing the words “anticipate,” “believe,” “estimate,” “expect,” “intend”, “goal,” “may”, “might,” “plan,” “predict,” “project,” “target,” “potential,” “will,” “would,” “could,” “should,” “continue,” and similar expressions. These forward-looking statements include statements about the RZ358 Expanded Access Program, the Investigational New Drug (IND) application for RZ358, the ability of the U.S. Ersodetug to become an effective treatment for congenital hyperinsulinism, the effectiveness or future effectiveness of the U.S. Ersodetug to become an effective treatment for congenital hyperinsulinism, and statements regarding clinical trial timelines for RZ358. These forward-looking statements are based on information currently available to the Company and its current plans or expectations, and are subject to a number of uncertainties and risks that could significantly affect current plans. Such forward-looking statements involve substantial risks and uncertainties that could cause the Company’s development programs, future results, performance or achievements to differ significantly from those expressed or implied by the forward-looking statements. Such risks and uncertainties include, among others, those related to market and other financial conditions, the potential completion of the public offering, satisfaction of customary closing conditions related to the public offering and other factors discussed in the “Risk Factors” section contained in the preliminary prospectus supplement and the reports that the Company files with the SEC. Any forward-looking statements represent the Company’s views only as of the date of this press release. The Company anticipates that subsequent events and developments will cause its views to change. While the Company may elect to update these forward-looking statements at some point in the future, the Company specifically disclaims any obligation to do so except as required by law.

Contacts:

Rezolute, Inc.
Christen Baglaneas
cbaglaneas@rezolutebio.com
508-272-6717

LHA Investor Relations
Tirth T. Patel
tpatel@lhai.com
212-201-6614

FAQ

What is the purpose of Rezolute's Phase 3 study for RZ358 (RZLT)?

The Phase 3 study aims to evaluate RZ358 (ersodetug) for treating hypoglycemia in patients with tumor hyperinsulinism (HI), a rare disease condition.

When will Rezolute (RZLT) begin patient enrollment for the RZ358 tumor HI study?

Rezolute plans to commence patient enrollment for the RZ358 tumor hyperinsulinism study in the first half of 2025.

What is the primary endpoint of Rezolute's Phase 3 study for RZ358 (RZLT)?

The primary endpoint is the change in Level 2 (moderate) and Level 3 (severe) hypoglycemia events as measured by self-monitored blood glucose.

How many participants will be included in Rezolute's Phase 3 study for RZ358 (RZLT)?

The study will include 24 participants, with the possibility of enrolling up to 24 additional participants in an open-label arm.