The U.S. Food and Drug Administration has again designated Rafael Pharmaceuticals’ lead candidate CPI-613 an orphan drug, this time to further advance it in clinical trials as a potential treatment for Burkitt’s lymphoma.
This is the FDA fourth orphan drug designation granted to CPI-613. The others were for pancreatic cancer, acute myeloid leukemia, and myelodysplastic syndromes.
“CPI 613 is the only investigational drug which has orphan designation to treat this rare disease. Our motto ‘To Save A Life Is to Save a Universe’ illustrates our desire to develop potential treatments for these patients,” Sanjeev Luther, president and CEO of Rafael Pharmaceuticals, said in a press release.
CPI-613 is a small molecule that blocks the mitochondrial tricarboxylic acid (TCA) cycle — a metabolic pathway widely used by cancer cells to survive and proliferate.
By interfering with enzymes in this cycle, CPI-613 aims to prevent cancer cells from being able to produce energy at the high rate they need, potentially killing them. The candidate is also thought to increase the sensitivity of cancer cells to chemotherapeutic agents.
Burkitt’s lymphoma is a rapidly growing, aggressive blood cancer. Patients are usually treated with aggressive chemotherapy and immunotherapy as first-line therapies, but no approved treatments exist for patients who fail to respond to these approaches.
CPI-613 is being developed for patients with blood cancers who did not respond to standard care or whose disease has returned despite an initial response to treatment.
In a Phase 1 trial (NCT01034475) in people with advanced blood cancers, CPI-613 showed promising signs of efficacy in a Burkitt’s lymphoma patient who had relapsed twice after prior therapy — chemotherapy and immunotherapy, followed by a stem cell transplant.
The patient, a 19-year-old woman, received 17 cycles of CPI-613 (twice weekly for three consecutive weeks). After the third cycle, researchers detected a partial reduction of her tumor.
After the 17 cycles, the patient discontinued treatment to have the tumor surgically removed. A tumor sample revealed extensive cell death, thought to be a result of CPI-613 treatment. Clinical follow-up continued to show no evidence of the disease more than 36 months later.
These findings were reported in the study, “A Phase I Study of the First-in-Class Anti-Mitochondrial Metabolism Agent, CPI-613, in Patients with Advanced Hematologic Malignancies,” published in the journal Clinical Cancer Research.
The company is now planning a Phase 2 trial to evaluate CPI-613 in relapsed or refractory Burkitt’s lymphoma/leukemia and high-grade B-cell lymphoma patients, who carry a genetic alteration in the MYC, BCL2, and BCL6 genes.
The study will be led by Ariela Noy, MD, a medical oncologist for lymphoma and AIDS-associated cancers at the Memorial Sloan-Kettering Cancer Center in New York.
“We look forward to launching this study with CPI-613 for patients with relapsed/refractory Burkitt Lymphoma who do not have any viable treatment options. This could be a potentially life-saving therapy,” Noy said.