Date: 2016-04-01
Type of information: Positive opinion for the granting of a Market Authorisation in the US
Product name: Halaven®
Compound: eribulin
Therapeutic area: Cancer - Oncology
Action mechanism: mitotic inhibitor/tubulin binder. Eribulin is a non-taxane, microtubule dynamics inhibitor indicated for the treatment of patients with breast cancer who have previously received at least two chemotherapeutic regimens for metastatic disease and whose prior therapy should have included an anthracycline and a taxane. Eribulin belongs to a class of antineoplastic agents, the halichondrins, which are natural products, isolated from the marine sponge Halichondria okadai. It is believed to work by inhibiting the growth phase of microtubule dynamics without affecting the shortening phase and sequesters tubulin into non-productive aggregates.
Company: Eisai (Japan)
Disease: liposarcoma
Latest news: * On April 1, 2016, the Committee for Medicinal Products for Human Use (CHMP) has adopted a positive opinion recommending a change to the terms of the marketing authorisation for Halaven® (eribulin) The CHMP adopted a new indication as follows: "treatment of adult patients with unresectable liposarcoma who have received prior anthracycline containing therapy (unless unsuitable) for advanced or metastatic disease". The most common side effects among participants treated with Halaven® were fatigue, nausea, hair loss (alopecia), constipation, certain nerve damage causing weakness or numbness in the hands and feet (peripheral neuropathy), abdominal pain and fever (pyrexia). Halaven® may also cause low levels of infection-fighting white blood cells (neutropenia) or decreased levels of potassium or calcium. Serious side effects from treatment with Halaven® may include a decrease in white blood cell count, which can increase the risk of serious infections that could lead to death; numbness, tingling or burning in the hands and feet (neuropathy); harm to a developing fetus; as well as changes in heartbeat (QTc prolongation), that may also lead to death. The FDA granted the Halaven® application priority review status, intended to facilitate and expedite the development and review of certain drugs in light of their potential to benefit patients with serious or life-threatening conditions. Halaven also received orphan drug designation, which provides incentives such as tax credits, user fee waivers, and eligibility for exclusivity to assist and encourage the development of drugs for rare diseases * On July 31, 2015, Eisai announced that a type II variation application to extend the indication of Halaven® (eribulin) was submitted in the European Union for the treatment of patients with inoperable soft tissue sarcoma who have received prior chemotherapy for locally advanced or metastatic disease. Efficacy and safety have been established primarily in patients with leiomyosarcomas and liposarcomas (adipocytic sarcomas), which make up approximately 30% of all soft tissue sarcomas. Similar applications have also been submitted in the US and Japan.
* On January 28, 2016, the FDA approved Halaven® (eribulin mesylate) for the treatment of liposarcoma that cannot be removed by surgery (unresectable) or is advanced (metastatic). This treatment is approved for patients who received prior chemotherapy that contained an anthracycline drug. The efficacy and safety of Halaven® were evaluated in 143 clinical trial participants with advanced liposarcoma that was unresectable or had spread to nearby lymph nodes (locally advanced) or other parts of the body (metastatic), and who had been treated with chemotherapy. Participants were treated with either Halaven® or dacarbazine until their disease spread or until they were no longer able to tolerate the side effects of treatment. The study was designed to measure the length of time from the start of treatment until a patient's death (overall survival). The median overall survival for patients with liposarcoma receiving Halaven® was 15.6 months compared to 8.4 months for those who received dacarbazine.
In a pivotal Phase III study, the median overall survival benefit (OS) for eribulin was 13.5 months versus 11.5 months for dacarbazine representing a significant benefit (HR 0.768; 95% CI 0.618-0.954; p=0.017). Study 309 met its primary objective for OS for use in patients treated with eribulin compared to dacarbazine, the current treatment standard. These data were presented at an oral session at the American Society of Clinical Oncology (ASCO) in June 2015.
Study 309 was a randomised, open-label multicentre Phase III study comparing the efficacy and safety of eribulin in 452 patients (aged 18 or over) to dacarbazine. Patients with locally advanced or relapsed metastatic soft tissue sarcomas who had disease progression following standard therapies including an anthracycline and at least one other additional regimen were recruited. Patients in the study had either leiomyosarcomas or liposarcomas. In this study, the most common treatment-emergent adverse events observed in the Halaven arm were fatigue or asthenia, neutropenia, nausea, alopecia, and peripheral neuropathy, which was consistent with the known side-effect profile of Halaven.
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: 2016-01-28
UE authorization:
Favourable opinion UE: 2016-04-01
Favourable opinion USA:
Orphan status USA:
Orphan status UE:
Pediatric exclusivit _USA:
Pediatric exclusivity UE: OTC status: Other news:
