Rolapitant Shows Promise in Prevention of Chemo-Induced Nausea and Vomiting
FDA submission expected in mid 2014
Positive results have been reported from the third and final phase III trial of rolapitant (Tesaro, Inc.), an investigational neurokinin-1 (NK-1) receptor antagonist in development for the prevention of chemotherapy-induced nausea and vomiting (CINV).
The rolapitant arm in this trial, which enrolled patients receiving cisplatin-based, highly emetogenic chemotherapy (HEC), successfully achieved statistical significance over the standard-therapy arm for the primary endpoint as well as for all secondary endpoints.
The final phase III trial of rolapitant was an international, randomized, double-blind, active-controlled study that enrolled 532 cancer patients receiving cisplatin-based chemotherapy regimens at a dose equal to or greater than 60 mg/m2. The patients were randomly assigned to receive either control therapy (a 5-HT3 receptor antagonist plus dexamethasone) or oral rolapitant (200 mg) plus control.
The rolapitant arm successfully achieved statistical significance over the control arm for the primary endpoint of complete response (CR) in the delayed phase of CINV. In addition, the rolapitant arm successfully achieved statistical significance over the control arm for the key secondary endpoints of CR in the acute (0 to 24 hour) and overall (0 to 120 hour) phases of CINV for the secondary endpoint of no significant nausea and for all other secondary endpoints.
Safety and tolerability data for patients who received rolapitant were similar to the results for those who received control and were consistent with those of earlier clinical studies. The most frequently observed adverse events included fatigue, constipation, and loss of appetite.
Preparations continue in support of the submission of a new drug application (NDA) to the FDA in mid 2014. The oral rolapitant NDA will include data from a phase III study in patients receiving moderately emetogenic chemotherapy (MEC) in addition to one phase II and two phase III trials in patients receiving cisplatin-based HEC, including the newly announced phase III study. Results from the phase III trial of rolapitant in MEC and the prior phase III study in HEC were announced in December 2013.
Rolapitant is a selective NK-1 receptor antagonist with an extended plasma half-life that is being developed for the prevention of CINV. NK-1 receptors are highly concentrated in the brain and bind the neurokinin substance P. Activation of NK-1 receptors plays a central role in nausea and vomiting induced by emetogenic stimuli, including certain cancer chemotherapies. NK-1 receptor antagonists have been demonstrated to improve the management of nausea and vomiting experienced by cancer patients undergoing chemotherapy. The safety and tolerability of single and repeat doses of rolapitant have been assessed in more than 2,500 healthy volunteers and patients. Rolapitant is being developed in both oral and intravenous formulations.
CINV is estimated to affect more than 70% of cancer patients undergoing chemotherapy and, if not prevented, may result in a delay or discontinuation of chemotherapy treatment. Prolonged nausea and vomiting may result in unwanted weight loss, dehydration, and malnutrition as well as hospitalization.
Source: Tesaro, Inc.; May 12, 2014.