On October 28, 2021 Rafael Pharmaceuticals, Inc. ("Rafael" or the "Company"), a company focused on the growing field of cancer metabolism-based therapeutics, reported that the AVENGER 500 Phase 3 clinical trial evaluating the efficacy and safety of CPI-613 (devimistat) in combination with modified FOLFIRINOX (mFFX) as a first-line therapy in patients with metastatic adenocarcinoma of the pancreas did not meet its primary endpoint of overall survival (Press release, Rafael Pharmaceuticals, OCT 28, 2021, View Source [SID1234592091]).

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In this multi-national Phase 3 randomized clinical trial, 528 patients with metastatic adenocarcinoma of the pancreas who had no prior therapy were randomized to receive either devimistat in combination with modified FOLFIRINOX (mFFX) or FOLFIRINOX, a current standard of care chemotherapy regimen. Devimistat given with mFFX did not significantly improve overall survival (HR=0.95, p=0.66). The median overall survival in the devimistat and mFFX arm was 11.1 months, compared to 11.7 months in the FOLFIRINOX arm.

"These cancers are incredibly difficult to treat, with few to no effective treatments available, but Rafael took the risk because we will always fight for our patients," said Sanjeev Luther, President and CEO of Rafael Pharmaceuticals. "While we are disappointed by the outcomes of these well-designed and well-executed studies, we remain committed to furthering our research and development in cancer metabolism for the treatment of hard-to-treat cancers, as our other studies continue. I personally want to express my heartfelt appreciation to the patients, their loved ones, the researchers and principal investigators for their trust and support. I am also incredibly grateful to my team, who works tirelessly for the patients we treat."

"Pancreatic cancer carries a high mortality rate and is extremely difficult to treat, but promising earlier clinical data encouraged us to move into this advanced phase trial with devimistat. While these are not the results we all hoped for, we will not give up, and we are hopeful that devimistat with its novel mechanism of action will demonstrate efficacy in other studies," said Philip Philip, M.D., Ph.D., F.R.C.P, principal investigator and medical oncologist at the Karmanos Cancer Institute at Wayne State University. "We are working diligently to further analyze the data and determine the best plan of action to further assess the drug’s capabilities in the clinic."

Devimistat is also being evaluated in a Phase 3 study, ARMADA 2000, in patients with relapsed or refractory acute myeloid leukemia (AML). Following a prespecified interim analysis, the independent data monitoring committee has recommended that the trial be stopped due to lack of efficacy.

"Earlier clinical trial data demonstrated positive results, despite the challenges we face in treating AML," said Jorge Cortes, M.D., director of the Georgia Cancer Center at Augusta University. "We were all hoping for positive results, and while this trial did not meet our expectations, we will continue to test devimistat in other studies."

The company will work with investigators to complete a full evaluation of the data on both trials.

About CPI-613 (Devimistat)
CPI-613 (devimistat) is a first-in-class clinical lead compound of Rafael, which targets enzymes that are involved in cancer cell energy metabolism and are located in the mitochondria of cancer cells. Devimistat is designed to target the mitochondrial tricarboxylic acid (TCA) cycle, a process essential to tumor cell multiplication and survival, selectively in cancer cells. Devimistat substantially increases cellular stress and the sensitivity of cancer cells to a diverse range of chemotherapeutic agents. This synergy allows for potential combinations of devimistat with lower doses of these generally toxic drugs to be more effective with lower patient side effects. Combination with devimistat represents a diverse range of opportunities to substantially improve patients’ benefit in many different cancers. The U.S. Food and Drug Administration (FDA) has given Rafael approval to initiate pivotal Phase 3 clinical trials in pancreatic cancer (AVENGER 500) and acute myeloid leukemia (ARMADA 2000) and has designated devimistat as an orphan drug for the treatment of pancreatic cancer, acute myeloid leukemia, myelodysplastic syndrome, peripheral T-cell lymphoma, soft tissue sarcoma, Burkitt’s lymphoma and biliary tract cancer. The European Medicines Agency (EMA) has granted orphan drug designation to devimistat for pancreatic cancer, acute myeloid leukemia and Burkitt’s lymphoma.