Regulatory Decision Summary for Halaven

The safety and efficacy of the new indication was assessed based on data from three studies.

A phase 3 pivotal study, Study 309, provided data for patients of both liposarcoma and leiomyosarcoma subtypes and suggested a statistically significant overall survival (OS) benefit of 2 months for Halaven over dacarbazine in the intention to treat (ITT) analysis. No benefit in the secondary endpoint, progression free survival (PFS), was demonstrated. Subgroup analyses based on histologic subtypes of soft tissue sarcoma revealed a statistically significant OS and PFS benefit for Halaven versus dacarbazine in the liposarcoma subgroup. By contrast, no difference in OS or PFS was observed between Halaven and dacarbazine treatment in the leiomyosarcoma subgroup. As a result, the indication was revised to reflect the benefit of Halaven restricted to patients with the liposarcoma subtype of soft tissue sarcoma, while emphasizing the lack of demonstrated benefit in patients with leiomyosarcoma. Data from smaller Phase 2 studies (Study 207 and Study 217) with Halaven in patients similar to the target population were generally consistent with pivotal data with regard to the differential benefit of Halaven in patients with the liposarcoma subtype.

Overall, the safety profile in patients with soft tissue sarcoma was consistent with the known safety profile of Halaven. New safety concerns identified in clinical trials and in the post-market setting included gastroesophageal reflux disease, QT interval prolongation, blood lactate dehydrogenase increased, somnolence, dysuria, dysphonia, oropharyngeal pain, rhinorrhea, hypotension, low potassium, high calcium and bilirubin levels. Other serious adverse reactions for which there is a potential of a causal relationship to Halaven included sudden death, pneumonia, sepsis (including neutropenic sepsis is some cases fatal), dehydration, renal failure, pulmonary embolism, deep vein thrombosis, Stevens-Johnson syndrome, toxic epidermal necrolysis, atrial fibrillation and disseminated intravascular coagulation. Safety concerns are identified and managed via revised labeling and strict monitoring.

The benefit-risk profile of Halaven is favourable for adult patients with unresectable advanced or metastatic liposarcoma who have received prior anthracycline -containing treatments.