The partial clinical hold was placed on esodetug last year after historical data emerged showing liver toxicity in laboratory rats following treatment with the therapy.
In May 2024, California-based Rezolute completed a follow-up toxicology study in laboratory rats in which no liver issues were found. As a result, the FDA traced the previously observed liver toxicity back to the specific rat strain that had been used in the earlier preclinical studies. Rezolute’s shares were up 10.3% in early trading following the FDA’s lifting of the partial clinical hold.
Ersodetug is currently in phase 3 trials outside of the US and is being tested in patients with the rare genetic disorder congenital hyperinsulinism, which causes low blood sugar. Ersodetug is a fully human monoclonal antibody that binds to insulin receptors in the liver, muscles, and fat. Here, the antibody prevents insulin and other related substances from binding to the receptor, correcting the low blood sugar in the process. While ersodetug is being tested in patients with congenital hyperinsulinism, the company has stated that acquired forms may be treated as well.
Hyperinsulinism is a disorder in which the insulin-secreting beta cells in the pancreas are not able to understand the blood glucose level and continuously secret insulin, regardless of the glucose concentration in the blood. As a result, blood glucose levels can drop dangerously low, which can especially affect brain cells, resulting in brain cell damage or even cell death. If hyperinsulinism is not detected fast enough, the damage to the brain can manifest in seizures, learning difficulties, cerebral palsy, blindness, and even death.
Severe and continuous low blood sugar
Congenital hyperinsulinism occurs in one out of 25,000 to one out of 50,000 births. It is the most common cause of severe and continuous low blood sugar. Current treatment options involve the surgical removal of the pancreas or different medications.
Following the lifting of the partial clinical hold, Rezolute will start involving U.S. participants in the phase 3 sunRIZE trial, with patient enrollment expected to start in early 2025. The global trial is multi-center, double-blind, randomized, and placebo-controlled and will observe the safety and efficacy of ersodetug in patients with congenital hyperinsulinism. The first results are expected in late 2025.
“We are delighted that the FDA has completely removed the partial clinical holds and are allowing us to proceed in the US at all doses and in participants as young as three months of age as part of our ongoing global study,” said Nevan Charles Elam, founder and CEO of Rezolute.
“Coming on the heels of our recent announcement of FDA clearance of a separate phase 3 study in tumor-associated hyperinsulinism, we are in the unique and fortunate position to be advancing ersodetug in two phase 3 rare disease programs in the US and globally.”
