Merck KGaA said today it will end development of evofosfamide in advanced soft tissue sarcoma and advanced pancreatic adenocarcinoma, after the drug candidate failed to meet its primary endpoints in two Phase III studies.

Evofosfamide failed to improve overall survival significantly when combined with chemotherapy in the two indications, the company and partner Threshold Pharmaceuticals said in separate announcements.

The hypoxia-activated prodrug was the subject of the MAESTRO and TH-CR-406/SARC021 studies. The former study, whose name stood for MetAstatic or unrESectable pancreaTic adenocarcinoma, assessed patients with previously untreated, locally advanced unresectable or metastatic pancreatic adenocarcinoma who were treated with evofosfamide in combination with gemcitabine.

The combination therapy showed no statistically significant improvement compared with gemcitabine plus placebo, Threshold said. A total of 693 patients were randomized in the study.

In TH-CR-406/SARC021, which was being conducted with the Sarcoma Alliance for Research through Collaboration (SARC), patients with locally advanced unresectable or metastatic soft tissue sarcoma treated with evofosfamide in combination with doxorubicin showed no statistically significant improvement in OS compared with doxorubicin alone, Threshold added. A total of 640 patients were randomized in the study.

Detailed results from the two Phase III studies will be presented at upcoming international scientific meetings and published in peer-reviewed journals once data have been further analyzed, Merck and Threshold said.

“We are surprised and disappointed that these studies did not show that evofosfamide could extend the lives of patients with these two difficult-to-treat diseases,” Threshold CEO Barry Selick, Ph.D., said in a company statement. “While we believe there remains substantial data to support the role of hypoxia in cancer treatment resistance, we are deeply frustrated with our inability in these trials to impact that in a meaningful way.”

Merck bought rights to develop evofosfamide in 2012, agreeing to pay Threshold €19 million ($20.5 million) upfront. The deal included up to €41.5 million ($44.9 million) in milestone payments by Merck to Threshold.

Merck said it would instead focus R&D efforts on more promising candidates—including the cancer immunotherapy avelumab, an anti-PD-L1 antibody being co-developed with Pfizer for more than 15 tumor types, “and all other priority programs in oncology, immuno-oncology and immunology.”

However, the company stopped short of formally ending the evofosfamide clinical program, for now.

“We will be making a quick decision on the future of the ongoing evofosfamide clinical program,” stated Luciano Rossetti, head of global research and development at Merck’s biopharma business.








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