Nektar Therapeutics and Daiichi Sankyo Europe have announced they signed an agreement for Nektar’s investigational drug therapy Onzeald (etirinotecan pegol) — formerly NKTR-102 – just after the completion of a Phase 3 clinical trial in patients with advanced breast cancer.

Breast cancer is the most frequently diagnosed cancer in women worldwide, with approximately 1.7 million new cases diagnosed in 2012 alone. There are nearly 250,000 newly diagnosed cases in the U.S. (and 470,000 in Europe) every year, and from 10 to 30 percent of patients with advanced breast cancer are also diagnosed with brain metastases.

Onzeald is the first long-acting topoisomerase 1 inhibitor with an extended half-life and a unique structure that is engineered to concentrate the drug in tumors. In patients, the drug candidate leads to greatly prolonged plasma SN38 exposure, when compared to irinotecan, yet peak SN38 concentrations are at least five to 10 times less, which might lead to a favorable tolerability profile.

The Phase 3 BEACON clinical trial was an open-label, randomized, multi-center study that enrolled 852 women with locally recurrent or metastatic breast cancer who had been previously treated with an anthracycline, taxane, and capecitabine therapies.

Nektar will submit a Marketing Authorization Application (MAA) filing this month 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. The application follows the Committee for Medicinal Products for Human Use (CHMP) decision to grant an accelerated assessment procedure for the planned Onzeald filing, also allowing an accelerated MAA later on.

The planned MAA is based on data from a subgroup of patients from the BEACON study involving single-agent Onzeald in patients with advanced breast cancer. In this subgroup of 67 patients — who also had a history of brain metastases — the treatment format led to:

• An improvement in median overall survival (OS) of 5.2 months vs. treatment with single-agent chemotherapy of physician’s choice (TPC) — (10 months for 4.8 months, a statistically significant result) — which included a range of potential treatments like ixabepilone, vinorelbine, gemcitabine, eribulin, or a taxane;
• In the primary analysis for the overall patient population in the BEACON study, Onzeald median overall survival was 2.2 months longer than TPC (12.4 months compared to 10.3 months);
• In the overall patient population included in the BEACON study, fewer patients receiving the drug candidate had grade 3 or worse adverse events (AEs) than those in the TPC arm (204, or 48 percent, compared to 256, or 63 percent);
• The most frequently reported grade 3 and above AEs in the Onzeald arm were “diarrhea (9.6 percent), neutropenia (9.6 percent), anemia (4.7 percent) and fatigue (4.5 percent),” and the most common grade 3 and above AEs reported in the TPC arm were “neutropenia (30.8 percent), anemia (4.7 percent), and dyspnea (4.4 percent).”

“This new collaboration with Daiichi Sankyo Europe allows Nektar to advance Onzeald to a potential conditional approval and availability in Europe as early as next year, and also enables us to retain ownership of the drug in the U.S. and rest of world,” said Howard W. Robin, Nektar Therapeutics’ president and CEO, in a press release.

“We are pursuing conditional approval for Onzeald based on highly promising data from our Phase 3 BEACON clinical trial in the pre-specified subgroup of patients with advanced breast cancer who have a history of brain metastases,” Robin said. “A diagnosis of brain metastases in women with advanced breast cancer is devastating and there are no therapies approved to treat this specific patient population.”

The agreement’s terms grant Nektar Therapeutics an upfront payment of $20 million – as well as an additional $60 million in milestone payments — and significant double-digit royalties on net sales in Europe, since the agreement grants Daiichi Sankyo Europe exclusive rights to Onzeald in the European Economic Area, Switzerland, and Turkey. Nektar Therapeutics will retain market rights in the U.S. and the remaining regions of the world.