EMA Grants Orphan Medical Product Designation to Elraglusib in Advanced PDAC

PDAC | Sebastian Kaulitzki – stock.adobe.com

The European Medicines Agency (EMA) has granted orphan medicinal product designation to elraglusib (9-ING-41), an investigational first-in-class glycogen synthase kinase-3 beta inhibitor, for the treatment of patients with advanced pancreatic ductal adenocarcinoma (PDAC).¹

“With limited treatment options available for patients with PDAC, the EMA orphan drug designation and FDA orphan drug designation granted to elraglusib for the same indication reflect elraglusib’s potential to address a critical need for people living with this aggressive disease with a notably poor prognosis,” Daniel Schmitt, president and chief executive officer of Actuate Therapeutics, stated in a news release. “This regulatory milestone, along with the recently announced positive interim results from our phase 2 [Actuate 1801] trial [NCT03678883] of elraglusib in patients with metastatic PDAC that showed a significant clinical benefit and antitumor activity, should expedite our efforts to advance elraglusib as a novel, potential treatment for metastatic PDAC.”

In 2023, the FDA granted orphan drug designation to elraglusib for the treatment of patients with pancreatic cancer.²

The phase 1/2 Acutate 1801 trial included an arm in the phase 2 portion specifically evaluating the agent in patients with advanced PDAC.¹ In this portion of the study, investigators examined elraglusib in combination with gemcitabine and nab-paclitaxel (Abraxane).

In part 3B of the phase 2 portion of Actuate 1801, patients with metastatic PDAC were randomly assigned to the combination of elraglusib, gemcitabine, and nab-paclitaxel or gemcitabine plus nab-paclitaxel alone as first-line therapy. Data previously reported from the interim analysis from part 3B demonstrated that treatment with the elraglusib regimen led to statistically significant increases in median overall survival (OS; HR, 0.63; P = 0.016) and 1-year OS rate (P = 0.002) vs gemcitabine plus nab-paclitaxel alone.

Data from part 2 of the study, which was nonrandomized, showed that as of the February 4, 2023, data cutoff, patients in the efficacy-evaluable population (n = 29) underwent a median duration of treatment with elraglusib plus gemcitabine and nab-paclitaxel of 5.5 months.³ The disease control rate was 51.7% (95% CI, 32.5%-70.6%), and the objective response rate was 37.9% (95% CI, 20.7%-57.7%).

The Actuate 1801 trial included 3 parts, and parts 1 and 2 have been completed.⁴ Part 1 evaluated elraglusib monotherapy in patients with advanced solid tumors in a standard 3+3 dose-escalation design until the maximum tolerated dose or recommended phase 2 dose was established. Part 2 combined elraglusib with standard anticancer agents in a 3+3 dose-escalation study design, specifically with 8 chemotherapy combination regimens including gemcitabine; doxorubicin; lomustine; carboplatin; irinotecan; nab-paclitaxel plus gemcitabine; paclitaxel plus carboplatin; and pemetrexed plus carboplatin.

In part 3 of the trial, patients with previously untreated metastatic or locally advanced PDAC were randomly assigned to receive elraglusib on days 1 and 4 of each week during 21-day cycles plus gemcitabine and nab-paclitaxel vs gemcitabine/nab-paclitaxel alone.

The primary end point of part 3 was 1-year OS rate.

“We look forward to reporting topline data from our phase 2 trial in the [first half of] 2025 and working closely with the EMA and the FDA to accelerate elraglusib’s clinical development program in metastatic pancreatic cancer,” Schmitt concluded in the news release.¹

References

1. Actuate Therapeutics receives EMA orphan medicinal product designation for elraglusib for the treatment of pancreatic cancer. News Release. Actuate Therapeutics. January 7, 2025. Accessed January 9, 2025. https://www.globenewswire.com/news-release/2025/01/07/3005368/0/en/Actuate-Therapeutics-Receives-EMA-Orphan-Medicinal-Product-Designation-for-Elraglusib-for-the-Treatment-of-Pancreatic-Cancer.html
2. Actuate Therapeutics receives FDA orphan drug designation for elraglusib for treatment of pancreatic cancer. Actuate Therapeutics. August 1, 2023. Accessed January 9, 2025. https://actuatetherapeutics.com/press_releases/actuate-therapeutics-receives-fda-orphan-drug-designation-for-elraglusib-for-treatment-of-pancreatic-cancer/
3. Mahalingam D, Saeed A, Powell SF, et al. Phase 2 study of elraglusib (9-ING-41), a glycogen synthase kinase-3b inhibitor, in combination with gemcitabine plus nab-paclitaxel (GnP) in patients with previously untreated advanced pancreatic ductal adenocarcinoma (PDAC). J Clin Oncol. 2023;41(suppl 1):e16289. doi:10.1200/JCO.2023.41.16_suppl.e16289
4. 9-ING-41 in patients with advanced cancers. ClinicalTrials.gov. Updated November 7, 2024. Accessed January 9, 2025. https://clinicaltrials.gov/study/NCT03678883