RedHill Biopharma Ltd., a specialty biopharmaceutical company primarily focused on the development and commercialization of late clinical-stage, proprietary, orally-administered, small molecule drugs for gastrointestinal and inflammatory diseases and cancer, said FDA has granted Yeliva (ABC294640) Orphan Drug designation for the treatment of cholangiocarcinoma.
Yeliva is a phase II, proprietary, first-in-class, orally-administered sphingosine kinase-2 (SK2) selective inhibitor with anticancer and anti-inflammatory activities, targeting multiple oncology, inflammatory and gastrointestinal indications. By inhibiting the SK2 enzyme, Yeliva blocks the synthesis of sphingosine 1-phosphate, a lipid signaling molecule that promotes cancer growth and pathological inflammation, the company said.
Cholangiocarcinoma is a highly lethal malignancy for which there is a strong need for more effective systemic treatments. Approximately 8,000 people are diagnosed with intrahepatic and extrahepatic bile duct cancers annually in the U.S., with recent studies showing an increased incidence of cholangiocarcinoma, mainly attributed to recent advancements in diagnosis of this disease.
Surgery with complete resection remains the only curative therapy for cholangiocarcinoma, however only a minority of patients are classified as having a resectable tumor at the time of diagnosis. Additional treatment options include radiation therapy and chemotherapy; however, the efficacy of these treatments in cholangiocarcinoma patients is also limited. Despite overall advances in the ability to diagnose and treat patients with cholangiocarcinoma, the prognosis for these relapse patients who have failed initial chemotherapy remains very poor, with an overall median survival of approximately one year.
The 5-year relative survival rates of intrahepatic and extrahepatic cholangiocarcinoma patients range between 2% to 30%, depending on the tumor type and stage at diagnosis. Final results from the phase I study with YELIVA in patients with advanced solid tumors confirmed that the study, conducted at the Medical University of South Carolina Hollings Cancer Center, successfully met its primary and secondary endpoints, demonstrating that the drug is well-tolerated and can be safely administered to cancer patients at doses that provide circulating drug levels that are predicted to have therapeutic activity.
Of the three patients with cholangiocarcinoma treated in the Phase I study, all of whom had prior therapy, one subject achieved a sustained partial response (Overall Survival = 20.3 months) and the other two subjects had prolonged stable disease (OS = 17.6 and 16.3 months).
RedHill said it plans to initiate a phase IIa clinical study with Yeliva in patients with advanced, unresectable, intrahepatic and extrahepatic cholangiocarcinoma in the third quarter of 2017. The single-arm study will evaluate Yeliva as a single agent in cholangiocarcinoma patients with a primary endpoint of determining the response rate of cholangiocarcinoma to this treatment.
A phase II study with Yeliva for the treatment of advanced hepatocellular carcinoma (HCC) is ongoing at MUSC Hollings Cancer Center. The study is supported by a $1.8 million grant from the NCI, awarded to MUSC, which is intended to fund a broad range of studies on the feasibility of targeting sphingolipid metabolism for the treatment of a variety of solid tumor cancers, with additional support from RedHill.
A phase Ib/II study with Yeliva for the treatment of refractory or relapsed multiple myeloma is ongoing at Duke University Medical Center. The study is supported by a $2 million grant from the NCI Small Business Innovation Research Programawarded to Apogee Biotechnology Corp., in conjunction with Duke University, with additional support from RedHill.
A phase I/II clinical study evaluating YELIVA in patients with refractory/relapsed diffuse large B-cell lymphoma as well as Kaposi sarcoma patients is ongoing at the Louisiana State University Health Sciences Center. The study is supported by a grant from the NCI awarded to Apogee, with additional support from RedHill. A phase Ib study to evaluate Yeliva as a radioprotectant for prevention of mucositis in head and neck cancer patients undergoing therapeutic radiotherapy is planned to be initiated in the third quarter of 2017, the company said.
