Date: 2016-06-01
Type of information: Licensing agreement
Compound: Onzeald™ (etirinotecan pegol)
Company: Nektar Therapeutics (USA - CA) Daiichi Sankyo (Japan)
Therapeutic area: Cancer - Oncology
Type agreement: licensing
Action mechanism: enzyme inhibitor/topoisomerase I inhibitor. Onzeald® is the first long-acting topoisomerase I inhibitor with an extended half-life and a unique structure that is designed to concentrate the drug in tumors. In patients, Onzeald® leads to greatly prolonged plasma SN38 exposure compared with irinotecan (elimination half-life of 37 days compared with 2 days) yet peak SN38 concentrations are at least 5- to 10-times less, which may also result in a favorable tolerability profile. Onzeald® was evaluated in a Phase 3, open-label, randomized, multicenter study (the BEACON study) that enrolled 852 women with locally recurrent or metastatic breast cancer, who have previously been treated with an anthracycline, taxane and capecitabine therapies.
Disease: advanced breast cancer and brain metastases
Details: * On June 1, 2016, Nektar Therapeutics announced that it has entered into an agreement with Daiichi Sankyo Europe for Nektar's investigational drug therapy, Onzeald® (etirinotecan pegol, NKTR-102), which has completed a Phase 3 clinical trial (the BEACON study) in patients with advanced breast cancer. The agreement grants Daiichi Sankyo Europe exclusive rights to market Onzeald® in Europe (EEA), Switzerland and Turkey. Nektar Therapeutics will retain rights to Onzeald® in the United States and the rest of the world. Nektar plans to submit an MAA filing in June 2016 seeking conditional approval from the European Medicines Agency (EMA) for the use of Onzeald® in the treatment of patients with advanced breast cancer and brain metastases. On May 26, 2016, the Committee for Medicinal Products for Human Use (CHMP) granted an accelerated assessment procedure for the planned Onzeald® filing, which provides for an accelerated MAA review timeline. Nektar will be responsible for sponsoring and funding the confirmatory trial which will support the Marketing Authorization Application (MAA) filing for Onzeald® in Europe. The data from the confirmatory trial can be used by Nektar for a potential U.S. new drug application (NDA) filing for Onzeald®. Nektar's planned MAA filing is based upon data from a subgroup of patients from the completed BEACON study of single-agent Onzeald® in patients with advanced breast cancer. In this subgroup of 67 patients who also had a history of brain metastases, treatment with single-agent Onzeald® resulted in an improvement in median overall survival (OS) of 5.2 months compared to treatment with a single-agent chemotherapy of physician's choice (TPC) (10 months vs. 4.8 months, P < 0.01). TPC included a choice of ixabepilone, vinorelbine, gemcitabine, eribulin or a taxane. In the planned primary analysis for the overall patient population in the BEACON study, Onzeald® median OS was 2.2 months longer than TPC (12.4 months vs. 10.3 months, P= 0.08).[3] In the overall patient population in the BEACON study, fewer patients in the ONZEALD arm had grade 3 or worse adverse events (AEs) than those in the TPC arm (204 [48%] vs. 256 [63%]; p < 0·0001).[3] The most common grade 3 and above AEs observed with Onzeald® were diarrhea (9.6%), neutropenia (9.6%), anemia (4.7%) and fatigue (4.5%). The most common grade 3 and above AEs observed with TPC were neutropenia (30.8%), anemia (4.7%), and dyspnea (4.4%). In order to satisfy the EMA's requirement for additional controlled data with the MAA for conditional approval, Nektar will sponsor a global, randomized Phase 3 trial of Onzeald® in approximately 350 patients with advanced breast cancer and brain metastases. The trial will compare Onzeald® to TPC and the primary endpoint in the trial will be OS. The trial will include a pre-specified interim analysis for OS which is to be conducted after 130 events have been observed in the trial. The FDA has also reviewed the Phase 3 study design with the Statistical Analysis Plan, and indicated the trial could serve as a potential registrational study by Nektar for purposes of seeking approval of Onzeald® to treat this patient population in the U.S.
Financial terms: Under the terms of the agreement, Nektar Therapeutics is entitled to an upfront payment of $20 million as well as an additional $60 million in milestone payments, based upon the achievement of European regulatory milestones and European sales of Onzeald®. Nektar is also entitled to significant double-digit royalties on net sales in Europe.
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