EDINBURGH, U.K.—NuCana plc announced today that the European Medicines Agency (EMA)’s Committee for Orphan Medicinal Products (COMP) has issued a positive opinion for orphan drug designation of Acelarin for the treatment of patients with biliary tract cancer. Acelarin is currently being evaluated, in combination with cisplatin, in a global Phase 3 study (NuTide:121) for the first-line treatment of patients with biliary tract cancer.
Biliary tract cancer, including cholangiocarcinoma, gallbladder and ampullary carcinoma, is cancer originating in the bile duct. Approximately 178,000 new cases of biliary tract cancer are diagnosed each year worldwide, with more than 18,000 of those diagnoses in the U.S. There are currently no agents approved for the treatment of biliary tract cancer; the worldwide standard of care in biliary tract cancer patients with locally advanced or metastatic disease is the combination of gemcitabine and cisplatin. Patients receiving this regimen have a median overall survival of 11.7 months.
“The receipt of a positive opinion for our orphan drug application in the European Union marks another important milestone in Acelarin’s development,” said Hugh S. Griffith, NuCana’s chief executive officer. “Acelarin in combination with cisplatin has achieved an approximate doubling in response rates when compared to the historical results achieved with the standard of care, gemcitabine plus cisplatin. NuTide:121 has the potential to establish Acelarin plus cisplatin as the first approved medicines for the treatment of patients with biliary tract cancer.”
NuTide:121 is a global, multi-center, randomized Phase 3 study that is enrolling up to 828 patients in approximately 120 sites across North America, Europe, Asia and Australia. Patients are being randomized 1:1 and treated with either a combination of Acelarin (725 mg/m2) plus cisplatin (25 mg/m2) or the current standard of care regimen, gemcitabine (1,000 mg/m2) plus cisplatin (25 mg/m2). The primary objectives of NuTide:121 are overall survival (OS) and objective response rate (ORR). Three interim analyses, including two designed to support accelerated approval, are planned as part of the Phase 3 study protocol, in addition to the final analysis.
Acelarin is derived from the nucleoside analogs gemcitabine and 5-fluorouracil. It is currently being evaluated in four clinical studies, including a Phase 3 study for patients with biliary tract cancer, a Phase 1b study for patients with biliary tract cancer, a Phase 2 study for patients with platinum-resistant ovarian cancer and a Phase 3 study for patients with metastatic pancreatic cancer for which enrollment has been suspended.
Based on discussions with the FDA and subject to any further regulatory guidance, NuCana believes that a statistically significant improvement in ORR at either of the first two interim analyses, supported by positive trends in other endpoints, could potentially allow for an accelerated approval of a new drug application (NDA) for Acelarin. Accelerated approval requires a confirmatory clinical study to verify the drug’s clinical benefit. If accelerated approval were to occur, NuTide:121 would continue and NuCana anticipates that data from subsequent analyses could provide the confirmatory data to support full, regular approval.
Orphan Drug Designation in the European Union (EU) is available to companies developing products for life-threatening or chronically debilitating conditions that affect fewer than five in 10,000 people in the region. This designation creates regulatory and financial incentives for NuCana, including reduced fees from the EMA during the development phase and a 10-year market exclusivity period in the EU following marketing authorization.
NuCana has previously received Orphan Drug Designation for Acelarin from the U.S. Food and Drug Administration’s Office of Orphan Products for the treatment of patients with biliary tract cancer.