Date: 2017-07-20
Type of information: Negative opinion for the granting of a Market Authorisation in the EU
Product name: Onzeald®
Compound: etirinotecan pegol
Therapeutic area: Cancer - Oncology - Rare diseases
Action mechanism:
- enzyme inhibitor/topoisomerase I inhibitor. Etirinotecan pegol consists of irinotecan that has been ‘pegylated. This long-acting topoisomerase I inhibitor has an extended half-life and a unique structure that is designed to concentrate the drug in tumors. It blocks topoisomerase I, an enzyme that is involved in copying
cell DNA, which is needed to make new cells. By blocking the enzyme, cancer cells are prevented from multiplying and they eventually die.
- 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.
Company: Nektar Therapeutics (USA - CA)
Disease: advanced breast cancer which has spread to the brain
Latest news:
- • On July 20, 2017, the Committee for Medicinal Products for Human Use (CHMP) adopted a negative
opinion, recommending the refusal of the marketing authorisation for Onzeald®, intended for the treatment of advanced breast cancer which has spread to the brain.
- Nektar Therapeutics presented the results of one main study involving 852 patients with breast cancer that had spread to other parts of the body who had been treated with at least 2 other cancer medicines. In this study, Onzeald® was compared with standard cancer medicines chosen by the treating doctor, and the main measure of effectiveness was overall survival.
- The CHMP considered that the benefit of Onzeald® in the treatment of breast cancer that had spread to the brain had not been sufficiently demonstrated. The claim of effectiveness relied on data from a subgroup of patients from a main study which, overall, failed to convincingly show the effectiveness of Onzeald®. The Committee considered that the data from
this subgroup, which were not supported by additional studies, were not sufficient to prove the effectiveness of Onzeald® in patients whose breast cancer had spread to the brain, even when analysed by different methods.
- • 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.
Patents:
Submission of marketing authorization application USA :
Submission of marketing authorization application UE:
Withdrawal of marketing authorization application USA:
Withdrawal of marketing authorization application UE:
US authorization:
UE authorization:
Favourable opinion UE:
Favourable opinion USA:
Orphan status USA: 2011-04-18
Orphan status UE:
Pediatric exclusivit _USA:
Pediatric exclusivity UE:
OTC status:
Other news:
Is general: Yes
