GlaxoSmithKline withdraws Zunrisa (casopitant) filings on safety fears

Vomiting drug Zunrisa/Rezonic (casopitant) filings of marketing applications worldwide have been withdrawn by GlaxoSmithKline as the drug need more data on its safety.

Zunrisa/Rezonic (casopitant) is indicated for vomiting following chemotherapy for cancer and post-operative nausea and vomiting.

GlaxoSmithKline, the world’s second-biggest drugmaker, filed regulatory applications for Zunrisa in a number of countries worldwide.

GlaxoSmithKline is currently communicating with those authorities and all study investigators, the company said in a press statement.

Based on the company’s assessment that significant further safety data would be required to support the registration of casopitant on a worldwide basis, which would take a considerable time to produce. Consequently, all on-going regulatory files for casopitant are being withdrawn, the company statement said.

GlaxoSmithKline submitted a new drug application to the US Food and Drug Administration in May last year on the basis of data from two Phase III trials for Rezonic/Zunrisa (casopitant).

Rezonic/Zunrisa (casopitant) is a novel, investigational NK-1 receptor antagonist.NK-1 receptor antagonists like casopitant block substance P from binding to receptors within the brain and have the potential to add benefit beyond standard 5-HT3 inhibitors.

Clinical data on Rezonic/Zunrisa (casopitant) showed a significant reduction in the number of patients experiencing chemotherapy-induced nausea and vomiting.

Casopitant when added to Zofran (ondansetron HCl), and dexamethasone in a single oral dose regimen  achieved this effect in patients taking highly emetogenic chemotherapy and those on moderately emetogenic chemotherapy treatment regimens.

Data demonstrated complete response rates of 86 percent for those patients given a single oral dose of casopitant together with the standard dual therapy in the HEC trial, and 73 percent for patients given either single oral or three-day oral doses of casopitant together with the standard dual therapy in the MEC trial.

Just one or two episodes of ighly emetogenic chemotherapy can have a significant impact on quality of life and may cause patients to delay or refuse therapy. Up to 40-50 percent of chemotherapy patients on standard anti-emetic treatment continue to experience breakthrough nausea and vomiting, particularly in the delayed setting.

GlaxoSmithKline had also submitted another new drug application for casopitant to the U.S. Food and Drug Administration for the indication of prevention of chemotherapy induced nausea and vomiting as an add-on therapy to the standard dual therapy of a 5-HT3 receptor antagonist, such as Zofran, and dexamethasone. Applications have been submitted for both the IV and oral formulations.

GlaxoSmithKline’s NDA submission also included the proposed indication of the prevention of postoperative nausea and vomiting.  NK-1 receptor antagonists like casopitant complement 5-HT3 receptor antagonists by acting on a different, but also important neurotransmitter system responsible for nausea and vomiting.

The multi-national, double-blind, controlled Phase III trial evaluated the tolerability and efficacy of a single oral dose and a three-day IV/oral dose regimen of casopitant or placebo added to standard dual therapy for reducing in patients receiving cisplatin-based HEC regimens.

Casopitant’s most commonly reported adverse events in the treatment arms were neutropenia, leukopenia and anemia, which occurred at a higher rate in the casopitant arms. The incidence of serious neutropenia adverse events was 2 percent in the active control arm, 1 percent in the single oral dose arm and 4 percent in the 3-day IV/oral arm.