Actuate Therapeutics' elraglusib (9-ING-41), a novel glycogen synthase kinase-3 beta (GSK-3β) inhibitor, has been granted Orphan Drug Designation by the U.S. Food and Drug Administration (FDA) for the treatment of pancreatic cancer. This designation aims to facilitate the development and regulatory pathway for elraglusib, addressing a critical unmet need in a cancer with a five-year survival rate of less than 10% in the United States.
Clinical Development of Elraglusib
Elraglusib is currently under evaluation in several clinical trials. The phase 1/2 1801 trial (NCT03678883) is assessing the safety and efficacy of elraglusib both as a monotherapy and in combination with cytotoxic agents in patients with refractory cancers. One arm of this trial specifically examines elraglusib in combination with gemcitabine and nab-paclitaxel (Abraxane) for patients with advanced pancreatic cancer.
According to Daniel Schmitt, president and chief executive officer of Actuate Therapeutics, the Orphan Drug Designation will enhance the company's ability to advance development and regulatory interactions with the FDA, bringing elraglusib to patients with this highly lethal malignancy.
Mechanism of Action and Preclinical Data
Overexpression of GSK-3β has been implicated in promoting tumor growth and resistance to chemotherapy in various cancers. Elraglusib, a first-in-class, maleimide-based small molecule, has demonstrated substantial antitumor activity in preclinical studies. Its mechanisms of action include reducing the expression of NF-κB genes, such as cyclin D1 and BCL-2, leading to the inhibition of cancer growth.
Ongoing Clinical Trials
In addition to the 1801 trial, elraglusib is being explored in combination with retifanlimab-dlwr (Zynyx), gemcitabine, and nab-paclitaxel in the RiLEY trial (NCT05239182) for advanced pancreatic adenocarcinoma. Another phase 2 trial (NCT05077800) is evaluating elraglusib in combination with FOLFIRINOX and losartan in patients with pancreatic cancer.
Dr. Andrew Mazar, chief operating officer of Actuate Therapeutics, noted that an open-label, randomized phase 2 study of elraglusib in combination with gemcitabine/nab-paclitaxel has been initiated for the frontline treatment of patients with metastatic pancreatic cancer, based on promising data from a completed single-arm phase 2 study. Additional investigator-led phase 2 studies are also in progress.
Benefits of Orphan Drug Designation
The FDA's Orphan Drug Designation is granted to investigational therapies addressing rare medical diseases or conditions affecting fewer than 200,000 people in the United States. This status provides several benefits to drug developers, including assistance in the drug development process, tax credits for clinical costs, exemptions from certain FDA fees, and seven years of post-approval marketing exclusivity.
