FDA Grants Orphan Drug Status to Devimistat for Biliary Cancer Treatment

The FDA has granted orphan drug designation to devimistat for the treatment of patients with biliary cancer,

The FDA has granted orphan drug designation to devimistat (CPI-613) for the treatment of patients with biliary cancer, according to a press release from Rafael Pharmaceuticals, Inc.

Devimistat is designed to selectively target the mitochondrial tricarboxylic acid (TCA) cycle in cancer cells. The agent also has orphan drug designations from the FDA for the treatment of patients with pancreatic cancer, acute myeloid leukemia, myelodysplastic syndrome, Burkitt’s lymphoma, peripheral T-cell lymphomas, and soft tissue sarcoma. Devimistat is among a small number of agents that have received 7 designations, underscoring a future pivot to cancer metabolism, according to the developer.

“Biliary cancer is often identified as an advanced stage cancer and considered aggressive with only modest response to existing treatment options for patients,” said Vaibhav Sahai, MBBS, MS, associate professor of medical oncology at the University of Michigan Medicine and the principal investigator on the phase 1b/2 clinical trial of devimistat in combination with gemcitabine and cisplatin for patients with biliary cancer, announced last year. “The orphan drug designation for devimistat showcases the importance of discovering these new treatment options.”

The study (NCT04203160) aims to determine the safety and efficacy of devimistat in patients with advanced biliary tract cancer when used with standard of care chemotherapy. Approximately 78 patients will be enrolled and randomized 2:1 to receive devimistat on days 1 and 8 of each 3-week cycle with gemcitabine and cisplatin or to gemcitabine and cisplatin alone on days 1 and 8 of each 3-week cycle. All study drugs are administered intravenously, and standard chemotherapy is given for up to 2 years or until disease progression or unacceptable toxicity.

As primary end points, the study is looking at the incidence of dose-limiting toxicity in phase 1 and overall response rate in phase 2. The secondary end points of the study include the median progression-free survival, median overall survival, and the incidence of toxicities.

Patients with pathologically or cytologically confirmed carcinoma of the biliary tract who are not eligible for curative resection, transplantation, or ablative therapies are eligible to enroll given they meet certain criteria. Patients are required to be at least 18 years of age or older with an ECOG performance status of 0 or 1, and adequate organ function. Individuals with tumors of mixed cholangiocarcinoma/hepatocellular carcinoma histology are not eligible to enroll, and those with a history of brain metastases, active malignancy, active or uncontrolled infection, and other conditions that may interfere with study treatment are also excluded.

“Biliary cancer affects a small subset of cancer patients, but the unique complexities of the disease create an incredible need to investigate and identify effective treatments,” said Sanjeev Luther, president, and chief executive officer of Rafael Pharmaceuticals, in a statement. “Therapies developed for hard-to-treat cancers need to consider the unique and complex intricacies of each disease. Having effective treatment options available to patients significantly improves the outlook for patients diagnosed with a rare cancer.”

The study of devimistat is ongoing with a target completion date of June 2025.


FDA grants Rafael Pharmaceuticals orphan drug designation for CPI-613® (devimistat) for treatment of biliary cancer. New release. Rafael Pharmaceuticals. June 29, 2021. Accessed June 29, 2021.