FDA Grants Orphan Drug Designation to Elraglusib for Pancreatic Cancer


The FDA has granted orphan drug designation to the GSK-3β inhibitor, elraglusib, for the treatment of patients with pancreatic cancer.

The FDA has granted orphan drug designation to the GSK-3β inhibitor, elraglusib (9-ING-41), for the treatment of patients with pancreatic cancer, according to an announcement from Actuate Therapeutics, Inc.1

The safety and efficacy of the agent as a monotherapy and in combination with cytotoxic agents is being explored in patients with refractory cancers as part of an ongoing phase 1/2 1801 trial (NCT03678883).2 In one arm of the trial, investigators specifically evaluated elraglusib plus gemcitabine and nab-paclitaxel (Abraxane) in patients with advanced pancreatic cancer.

“We are pleased with the FDA’s decision to grant orphan drug designation to elraglusib for the treatment of pancreatic cancer,” Daniel Schmitt, president and chief executive officer of Actuate Therapeutics, Inc. stated in a press release.1 “Pancreatic cancer remains an area of high unmet medical need, with less than 10% survival in the United States at 5 years. The orphan drug designation furthers our ability to advance development and regulatory interactions with the FDA to bring elraglusib to patients with this highly lethal malignancy.”

Overexpression of GSK-3β has been found to encourage tumor growth as well as resistance to chemotherapies in several cancers.2 As such, this has been established as a possible anticancer target in bladder cancer, breast cancer, colorectal cancer, glioblastoma, lung cancer, neuroblastoma, ovarian cancer, pancreatic cancer, prostate cancer, renal cancer, and thyroid cancers.

Preclinical data have indicated that the first-in-class, maleimide-based small molecule selective GSK-3β inhibitor has demonstrated substantial antitumor activity.2 The modes of action of elraglusib include reducing expression of NF-κB genes like cyclin D1, BCL-2, antiapoptotic protein, and B-cell lymphoma-extra large, as well as the downregulation of NF-κB; this results in the inhibition of cancer growth.

The 1801 trial was comprised of 3 parts. The first part utilized a standard 3+3 dose-escalation design that was applied to all dose cohorts analyzed until investigators identified the maximum tolerated dose or the recommended phase 2 dose. The second portion also utilized a 3+3 design; here, the agent was combined with 8 chemotherapy agents/combinations: gemcitabine, doxorubicin, lomustine, carboplatin, irinotecan, nab-paclitaxel plus gemcitabine, paclitaxel plus carboplatin, and pemetrexed plus carboplatin.

The agent is also under exploration in combination with retifanlimab-dlwr (Zynyx), gemcitabine, and nab-paclitaxel in patients with advanced pancreatic adenocarcinoma, as part of the ongoing RiLEY trial (NCT05239182).3 Another phase 2 trial (NCT05077800) is evaluating elraglusib in combination with FOLFIRINOX and losartan in patients with pancreatic cancer.4

“Based on the promising final data from our completed single-arm phase 2 study, we have initiated an open-label, randomized phase 2 study of elraglusib in combination with gemcitabine/nab-paclitaxel for the frontline treatment of patients with metastatic pancreatic cancer” said Dr Andrew Mazar, chief operating officer of Actuate Therapeutics, Inc., added in the press release. “Additional investigator-led phase 2 studies…are also in progress, emphasizing our commitment to developing elraglusib for the pancreatic cancer population.”


  1. Actuate Therapeutics receives FDA orphan drug designation for elraglusib for treatment of pancreatic cancer. News release. Actuate Therapeutics, Inc. August 1, 2023. https://actuatetherapeutics.com/press-releases/actuate-therapeutics-receives-fda-orphan-drug-designation-for-elraglusib-for-treatment-of-pancreatic-cancer/
  2. 9-ING-41 in patients with advanced cancers. ClinicalTrials.gov. Updated July 19, 2023. Accessed August 1, 2023. https://clinicaltrials.gov/study/NCT03678883
  3. 9-ING-41 plus retifanlimab and gemcitabine/nab-paclitaxel in patients with advanced pancreatic adenocarcinoma (RiLEY). ClinicalTrials.gov. Updated July 13, 2023. Accessed August 1, 2023. https://classic.clinicaltrials.gov/ct2/show/NCT05239182
  4. FOLFIRINOX + 9-Ing-41 + losartan in pancreatic cancer. ClinicalTrials.gov. Updated June 9, 2022. Accessed August 1, 2023. https://classic.clinicaltrials.gov/ct2/show/NCT05077800
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