FDA Expands Indication for Nausea/Vomiting Drug Fosaprepitant (Emend)

Only intravenous NK-1 receptor antagonist approved in U.S. for use in MEC

The FDA has approved a supplemental new drug application (sNDA) for intravenous (IV), single-dose fosaprepitant dimeglumine (Emend, Merck), a substance P/neurokinin-1 (NK1) receptor antagonist, in combination with other antiemetic medications, for the prevention of delayed nausea and vomiting in adults receiving initial and repeat courses of moderately emetogenic chemotherapy (MEC). Fosaprepitant has not been studied for the treatment of established nausea and vomiting.

The FDA approval was supported by data from a phase 3 study in which single-dose fosaprepitant for injection, combined with other antivomiting medications, provided greater protection from delayed nausea and vomiting after the administration of MEC compared with an active control regimen. With the new approval, fosaprepitant for injection is the first IV, single-dose NK1 receptor antagonist approved in the U.S. for both highly emetogenic chemotherapy (HEC) and MEC.

In the randomized, parallel-group, double-blind, active comparator-controlled study, fosaprepitant dimeglumine for injection (150 mg) as a single IV infusion in combination with ondansetron and dexamethasone (referred to as the Emend regimen; n = 502) was compared with ondansetron and dexamethasone (control regimen; n=498) in patients receiving MEC. The study’s primary endpoint was the complete response (defined as no vomiting and no use of rescue therapy) in the delayed phase (25 to 120 hours after the initiation of chemotherapy) of chemotherapy-induced nausea and vomiting (CINV). A 79% complete response rate was observed with the Emend regimen compared with 69% with the control regimen (P < 0.001).

The most common adverse events reported with the Emend regimen compared with the control regimen were fatigue (15% vs. 13%, respectively), diarrhea (13% vs. 11%), neutropenia (8% vs. 7%), asthenia (4% vs. 3%), anemia (3% vs. 2%), peripheral neuropathy (3% vs. 2%), leukopenia (2% vs. 1%), dyspepsia (2% vs. 1%), urinary tract infection (2% vs. 1%), and pain in extremity (2% vs. 1%).

Fosaprepitant dimeglumine for injection is an IV prodrug of aprepitant, the oral formulation of Emend. When administered by injection, fosaprepitant is rapidly converted in the body to aprepitant, which is a selective high-affinity antagonist of human substance P/NK1 receptors. Aprepitant has little or no affinity for serotonin (5-HT3), dopamine, and corticosteroid receptors––the targets of current therapies for CINV.

Fosaprepitant dimeglumine for injection, in combination with other antiemetic agents, is indicated in adults for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of HEC, including high-dose cisplatin, and for the prevention of delayed nausea and vomiting associated with initial and repeat courses of MEC.

Source: Merck; February 4, 2016.