Awaiting
Phase 3 Results for Tumor-Mediated Hyperinsulinism… FDA Meeting Key for Congenital HyperinsulinismAccording to a recent announcement by Resolute, the company has completed patient enrollment for “upLIFT,” a global Phase 3 clinical trial of Ersodetug in patients with tumor-mediated hyperinsulinism. Topline data, the key results, are expected to be released in mid-December.
Ersodetug is a novel antibody drug designed to reduce excessive insulin receptor activity and thereby improve hypoglycemia. Resolute acquired the candidate, which had been under development by U.S.-based Zoma, in 2017 and is currently conducting further development. It is being developed with hypoglycemia caused by congenital hyperinsulinism and tumor-induced hyperinsulinism as its primary indications.
Tumor-induced hyperinsulinism is a condition in which a tumor secretes excessive insulin or produces substances that act like insulin, causing hypoglycemia. Ersodetug is intended as a treatment to manage severe hypoglycemia caused by the tumor, rather than to remove the tumor itself.
The upLIFT trial is being conducted in 16 patients with insulinomas or non-islet cell tumors who require continuous intravenous glucose infusion because their hypoglycemia caused by tumor-induced hyperinsulinism cannot be controlled. The primary endpoint is the proportion of patients who reduce their intravenous glucose infusion rate by at least 50% compared to baseline levels during the 8-week main treatment period. This evaluates the extent to which the drug can reduce the amount of glucose that must be supplied externally to maintain blood glucose levels.
HANDOK Inc. holds the domestic commercialization rights for Ersodetug for both neoplastic and congenital hyperinsulinism. A HANDOK Inc. official stated, “We still need to wait a little longer to determine the timing of its introduction in Korea,” but added, “Once discussions in the U.S. are concluded and the next steps are finalized, the direction for its launch in Korea will also be clarified.”
Ersodetug’s use for congenital hyperinsulinism is undergoing a separate clinical trial and approval process. However, in the Phase 3 “sunRIZE” trial, the reduction in hypoglycemic events compared to the placebo was not statistically significant, so the trial failed to meet its primary endpoint. Subsequently, Resolute submitted continuous glucose monitoring (CGM) data and other materials, and announced on the 5th that the FDA had recommended holding a “pre-BLA meeting”—a pre-submission consultation—prior to filing a Biologics License Application (BLA).
It is understood that the specific date for the meeting has not yet been determined. The key issue is whether the approval application can proceed based on the existing clinical data. This is because if additional clinical trials are required, the development period and costs will increase, which could also affect the timing of its introduction in Korea. A HANDOK Inc. official explained, “We are currently at the stage of discussing whether additional clinical trials are needed and what else is required,” adding, “While it is true that our ultimate goal is a domestic launch, specific details can only be provided once a conclusion is reached regarding the next steps.”
Bile Duct Cancer Under FDA Consultation, Stomach Cancer in Expanded Clinical Trials… Attention on Follow-up ResultsHANDOK Inc. expects the commercialization of Ersodetug to be the fastest among its open innovation projects. “Tobesimig,” a bile duct cancer treatment developed in collaboration with ABL Bio Inc., and “Zibastomig,” a stomach cancer treatment, are also cited as key projects with promising
follow-upresults.
“Tobesimig,” a bile duct cancer treatment, is a bispecific antibody that simultaneously inhibits two pathways involved in the formation of new blood vessels that supply blood to tumors; HANDOK Inc. holds the domestic commercialization rights. Overseas, Compass Therapeutics is developing the drug.
However, regulatory consultations remaining before a marketing authorization application can be submitted also pose a variable for Tobesimig. Compass Therapeutics announced on the 22nd of last month that the FDA had recommended conducting a trial to demonstrate a survival benefit prior to submitting the marketing authorization application. Although Tobesimig demonstrated improvements in objective response rate (ORR) and progression-free survival (PFS) in Phase 2 and 3 clinical trials, it did not achieve statistical significance in overall survival (OS).
However, Compass Therapeutics maintains that, given the existing results and patients’ unmet medical needs, a new trial is not necessary prior to the marketing authorization application, and the company plans to continue further discussions with the FDA.
The new stomach cancer drug “Zibastomig” is also worth noting. HANDOK Inc. holds the domestic rights, and it is being jointly developed by ABL Bio Inc. and U.S.-based NovaBridge Biosciences. It is a bispecific antibody that targets claudin 18.2 (CLDN18.2), which is expressed in cancer cells, and stimulates 4-1BB, a signal that activates immune cells.
A Phase 2 clinical trial combining the drug with nivolumab and chemotherapy is currently underway. ABL Bio Inc. plans to present the latest safety and efficacy data from a previously conducted Phase 1b combination therapy trial at the European Society for Medical Oncology (ESMO) conference on the 25th.
In addition, HANDOK Inc.’s collaborative pipeline includes “GX-H9,” a long-acting growth hormone therapy currently under development with Genexine, Inc.; “SBP-101,” an oral immunotherapy for cancer from Spark BioPharma; and “SleepQ,” a digital therapy for insomnia launched in collaboration with Welt.
An industry insider stated, “New drugs for which we proactively secured domestic rights are entering late-stage clinical trials or the regulatory approval process,” adding, “If we can successfully expand our product portfolio and establish these promising new drugs as new revenue streams by carefully selecting and introducing them, this will be recognized as a business success of open innovation.”
