On September 2 (U.S. time), Rezolute announced that it has reached an agreement with the U.S. Food and Drug Administration (FDA) to significantly simplify the clinical development pathway for RZ358 (ersodetug) in the Phase 3 upLIFT trial for the treatment of hypoglycemia caused by tumor-mediated hyperinsulinism.

Under the agreement, the previous double-blind, randomized, placebo-controlled design will be replaced with a streamlined single-arm, open-label trial enrolling a minimum of 16 patients. This reflects Rezolute’s current focus on patient recruitment. The FDA also acknowledged that results from Rezolute’s pivotal sunRIZE study in congenital hyperinsulinism—expected to report topline data in December—could serve as key clinical evidence supporting the broader applicability of RZ358 across multiple forms of hyperinsulinism.

Nevan Charles Elam, CEO and Founder of Rezolute, stated:
“The FDA’s new leadership has expressed a strong commitment to responsibly simplifying clinical development for rare diseases where clinical benefit and mechanistic rationale are well established. This agreement is a prime example of that innovative approach and is based on positive outcomes from treating more than 10 patients with tumor-mediated hyperinsulinism through our Expanded Access Program over the past two years.”

Brian Roberts, M.D., Chief Medical Officer of Rezolute, added:
“The streamlined design of the upLIFT trial is highly meaningful for patients, families, and clinicians dealing with severe hypoglycemia caused by tumor-mediated hyperinsulinism. We will focus on executing the upLIFT trial and leveraging the robust clinical foundation established in congenital hyperinsulinism to accelerate development and deliver this therapy efficiently.”

Rezolute is a U.S.-based biotech company developing targeted therapies for rare metabolic diseases, including RZ358 for hyperinsulinism and RZ402, an oral therapy for diabetic macular edema. RZ358 is currently in Phase 3 trials for two indications: congenital hyperinsulinism and tumor-mediated hyperinsulinism. Handok holds commercialization rights for RZ358 and RZ402 in Korea and continues to collaborate with Rezolute throughout the development process.