Breakthrough Clinical Results
Actuate Therapeutics announced positive Phase 2 results for elraglusib (elra) in combination with gemcitabine and nab-paclitaxel (GnP) for metastatic ductal pancreatic cancer. The trial showed a doubling of the one-year survival rate compared to GnP alone (44.1% vs 22.3%). Elraglusib, a GSK-3β inhibitor, appears to enhance the immune response, making tumors more vulnerable to existing therapies. Actuate plans to discuss registration and commercialization with the FDA and EMA. Further trials are planned to explore elraglusib's potential in combination with other therapies for various cancers.
Key Highlights
- Phase 2 trial of elraglusib + GnP doubled the one-year survival rate in metastatic pancreatic cancer patients compared to GnP alone.
- Elraglusib demonstrated a novel mechanism of action by enhancing the immune response and making tumors more susceptible to treatment.
- Actuate plans to engage with the FDA and EMA to pursue registration and commercialization of elraglusib.
- Further trials are planned to explore elraglusib's potential in combination with other therapies for various cancers.
Incidence and Prevalence
Global Estimates of Metastatic Pancreatic Cancer
Pancreatic cancer remains one of the deadliest malignancies with an overall 5-year survival rate of just 13%. It currently ranks as the fourth most common cause of cancer death in the western world, primarily due to its low treatment success rate.
The incidence of pancreatic cancer has tripled in the United States over the past 50 years, with forecasts suggesting that by 2030, pancreatic cancer will exceed other cancer types in prevalence. Recent epidemiological data shows varying trends globally:
- In China, the age-standardized incidence rate (ASIR) increased from 3.17 per 100,000 in 1990 to 5.78 per 100,000 in 2019
- The high-income Asia-Pacific region reported an age-standardized prevalence rate (ASPR) of 11.2 per 100,000 population in 2021
- In Brazil, pancreatic cancer incidence rose from 5.33 to 6.16 per 100,000 inhabitants between 2000-2019
- According to SEER data, pancreatic cancer incidence continued to rise in all ethnicities from 2000-2017
Carcinomas represent the most common morphological sub-type, comprising 90% or more of all pancreatic tumors worldwide. For ductal adenocarcinoma specifically, rates showed positive trends in all races with annual percent change (APC) of ≥6% for females and ≥6.5% for males. Males generally had higher incidence than females with a male to female Incidence Risk Ratio (IRR) of 1.32.
Regarding survival outcomes, age-standardized one-year net survival for carcinomas ranged from 10% to 30%, while five-year survival remained poor (less than 10%). Metastasis is a significant factor associated with calpain-1 overexpression and TNM stage. Patients with low calpain-1 expression demonstrated increased overall survival compared to those with high calpain-1 levels (28.7±4.1 vs. 17.0±2.3 months).
For patients with borderline resectable pancreatic cancer (BRPC) and locally advanced pancreatic cancer (LAPC) who received neoadjuvant therapy, resected patients had better survival than nonresected, with median survival 22.4 vs 12.7 months; and 1-, 3-, and 5-yr survival: 86.4%, 38.9%, 26.9% vs 52.2%, 1.5%, 0%, respectively.
The disease presents considerable challenges due to the lack of prominent symptoms in early stages, restricted options for early detection, rapid progression, and unfavorable outcomes. Pancreatic cancer is characterized as a cold tumor with a unique immunosuppressive tumor microenvironment.
Despite promising therapeutic approaches including targeted matrix therapy, targeted metabolic therapy, targeted mutant gene therapy, immunosuppressive therapy, and cancer vaccines, clinical results have been largely disappointing, contributing to the persistently poor survival rates observed worldwide.
Economic Burden
Economic Burden of Treating Metastatic Pancreatic Cancer in USA and Europe
United States
The economic burden of treating metastatic pancreatic cancer in the USA is substantial, with significant differences between insurance types. According to 2022 data, the total cost of care for commercially insured patients ranged from $95,426 to $116,325 depending on treatment regimen. In contrast, Medicare patients faced considerably lower costs ranging from $39,777 to $40,390. This creates a striking 3:1 ratio of total care costs between commercially insured and Medicare patients.
The most recent 2025 data shows that NALIRIFOX therapy for metastatic pancreatic ductal adenocarcinoma (mPDAC) costs $150,437 compared to $130,683 for gemcitabine plus nab-paclitaxel (GemNab). The incremental cost-effectiveness ratio (ICER) for NALIRIFOX was calculated at $155,602.83 per quality-adjusted life year (QALY), slightly exceeding the highest conventional US willingness-to-pay threshold of $150,000/QALY.
Treatment setting significantly impacts costs. A 2021 study found patients receiving chemotherapy at community oncology centers had 41% lower mean total cost of care compared to hospital outpatient settings. For resectable pancreatic cancer, FOLFIRINOX cost $40,831 higher than GemNab ($99,669 vs. $58,837).
Europe
In Europe, the economic burden varies by country:
In Belgium (2024 data), pancreatic cancer had one of the highest attributable costs per patient, ranking third after lung cancer and liver cancer.
Catalonia, Spain (2023 data) showed age-dependent cost variations: - For patients under 60 years, the mean cost for the first year was €17,730 with surgery and €5,398 for pharmacological treatment of unresectable disease - For patients over 80 years, these costs decreased to €15,339 and €1,845 respectively
Sweden (2012 data) reported: - Direct treatment cost per patient at €16,066 for remaining lifetime - Hospitalization accounted for 60% of lifetime treatment costs - Costs varied by disease stage: resectable tumor (€19,809), locally advanced (€14,899), and metastatic disease (€16,179) - Productivity loss was estimated at €287,420 per patient under 65 years, with premature mortality accounting for 79%
A 2023 Japanese study found that median monthly medical costs were highest in the first month of treatment, with gemcitabine plus nab-paclitaxel having the highest first-month cost at $6,813 USD.
Treatment Accessibility
Only 18% of pancreatic cancer patients received surgery with curative intent, mostly younger patients. Chemotherapy was used less frequently in patients of advanced age, though survival in treated patients was comparable across age groups. Half of all diagnosed patients received no specific treatment, highlighting significant gaps in care delivery.
Study Design Parameters
Study Design Parameters and Endpoints in Key Metastatic Pancreatic Cancer Trials
Trial Designs
Randomized controlled trials (RCTs) are the primary study design for evaluating treatments for metastatic pancreatic cancer. The E6201 trial enrolled 832 patients to compare overall survival of standard weekly gemcitabine versus fixed-dose rate gemcitabine or gemcitabine plus oxaliplatin (GEMOX). This study was designed to detect a 33% difference in median survival (hazard ratio ≤0.75) with 81% power while maintaining a significance level of 2.5%.
Trials typically include patients with metastatic or locally advanced pancreatic cancer, normal organ function, and performance status of 0 to 2. A meta-analysis of 10 RCTs included 1340 patients split almost equally between neoadjuvant therapy and upfront surgery, with gemcitabine-based neoadjuvant therapy used in most studies.
Some trials employ specific designs, such as the Simon 2-stage design used in a 2012 phase II study of eribulin. Treatment arms in various studies have included FOLFIRINOX (5-fluorouracil, oxaliplatin, irinotecan, and leucovorin), gemcitabine-based chemotherapy, and combinations like nab-paclitaxel plus gemcitabine.
Key Endpoints
Overall survival (OS) is the primary endpoint in most trials, including the MPACT and TLP0-001 trials. Disease-free survival (DFS) and progression-free survival (PFS) are important secondary endpoints.
The E6201 trial reported median survival of 4.9 months for gemcitabine, 6.2 months for fixed-dose rate gemcitabine, and 5.7 months for GEMOX. One-year survival rates were 16% for gemcitabine, 21% for fixed-dose rate gemcitabine, and 21% for GEMOX.
In the MPACT trial, results showed median OS of 10.5 versus 8.4 months (HR, 0.71; P = 0.009) for nab-paclitaxel plus gemcitabine versus gemcitabine alone. The objective response rate (ORR) by RECIST criteria was 31% versus 11% (P < 0.001).
Other important endpoints include disease control rate (DCR) and metabolic response rates measured by PET imaging. In the MPACT trial, metabolic response by PET was associated with longer OS (median 11.3 versus 6.9 months; HR, 0.56; P < 0.001), and higher metabolic response rates were observed for nab-paclitaxel plus gemcitabine versus gemcitabine alone (best response: 72% versus 53%, P = 0.002).
Prognostic Factors
Several factors significantly impact outcomes, including Eastern Cooperative Oncology Group performance status (HR 1.48; P < 0.001), use of second-line treatment (HR 1.51; P < 0.001), and UICC stage (III versus IV) (HR 1.34, P = 0.002). Age above 65 years and fewer than nine cycles of chemotherapy are risk factors linked to adverse OS and DFS.
Locally advanced tumors after neoadjuvant treatment, lymph node disease, and histological tumor regression grade 2 and 3 are associated with worse outcomes.
Recent developments include the use of multianalyte signatures including liquid biopsy and traditional clinical variables to improve prognostication, with circulating tumor cells (CTCs) and circulating tumor KRAS (ctKRAS) providing complementary prognostic information.
No Information Available on Elraglusib Combination Therapy for Non-Pancreatic Indications
Based on a comprehensive review of available data, there is no information found regarding the use of elraglusib in combination with gemcitabine and nab-paclitaxel for indications other than metastatic pancreatic cancer.
The combination therapy of these three agents (elraglusib + gemcitabine + nab-paclitaxel) has not been documented in clinical trials for any alternative indications in the available information. Consequently, there are no intervention models or trial designs to report for this specific combination therapy in non-pancreatic cancer settings.
Without documented clinical trials using this specific combination for other indications, details regarding dosing regimens, administration protocols, or clinical trial phases for non-pancreatic malignancies cannot be provided.
Healthcare professionals interested in this combination therapy should consult the latest clinical trial registries and medical literature for the most current information, as new trials may be initiated that are not reflected in the currently available data.