The FINANCIAL — Merck, known as MSD outside the United States and Canada, on September 2 announced that the U.S. Food and Drug Administration (FDA) has approved a supplemental New Drug Application (sNDA) for EMEND (aprepitant) capsules, a substance P/neurokinin 1 (NK1) receptor antagonist.
With this expanded indication, EMEND capsules are now approved for use in combination with other antiemetic agents in patients 12 years of age and older and patients less than 12 years who weigh at least 30 kg (approximately 66 pounds) for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic cancer chemotherapy (HEC) including high-dose cisplatin, as well as for the prevention of nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy (MEC). EMEND has not been studied for treatment of established nausea and vomiting. Chronic continuous administration of EMEND is not recommended because it has not been studied, and because the drug interaction profile may change during chronic continuous use, according to Merck.
With this approval, EMEND is the first and only NK1 receptor antagonist to be approved for the prevention of acute and delayed phases of chemotherapy-induced nausea and vomiting (CINV) in patients 12 to 17 years of age and patients less than 12 years who weigh at least 30 kg receiving HEC or MEC. The approval was supported by data from a pivotal Phase 3 study that showed adding EMEND to a standard regimen for prevention of CINV in HEC or MEC regimens resulted in a reduction of emetic events.
EMEND is contraindicated in patients with any known sensitivity to any component of this drug. EMEND is also contraindicated for patients taking pimozide.
There is no commercially available dosage formulation of EMEND appropriate for patients less than 12 years of age and weighing less than 30 kg. Therefore, EMEND is indicated for the prevention of nausea and vomiting associated with HEC or MEC in patients 12 years of age and older and patients less than 12 years of age who weigh at least 30 kg.
Data Supporting the Expanded FDA Approval
The FDA approval of this expanded indication for EMEND (aprepitant) was based in part on findings from a randomized, double-blind, active-comparator-controlled clinical study that assessed EMEND in combination with ondansetron (EMEND regimen) compared to ondansetron alone (control regimen) for the prevention of CINV in patients 12 to 17 years of age and patients less than 12 years of age who weighed at least 30 kg (n=63 and 69, respectively) receiving HEC or MEC. Intravenous dexamethasone was permitted at the discretion of the physician. The primary endpoint was complete response (no vomiting, retching and no use of rescue medication) in the delayed phase (25 to 120 hours following initiation of chemotherapy). Other pre-specified endpoints included: complete response in the acute phase (0 to 24 hours following initiation of chemotherapy), complete response in the overall phase (up to 120 hours following initiation of chemotherapy), and safety and tolerability. For the population aged 12 to 17 years and patients less than 12 years who weighed at least 30 kg (n=132), data included in the label show that in the delayed phase, a 49.2 percent (n=31/63) complete response rate was observed in the EMEND regimen compared to 18.8 percent (n=13/69) in the control regimen; in the acute phase, a 55.6 percent (n=35/63) complete response was observed in the EMEND regimen compared to 37.7 percent (n=26/69) in the control regimen; and, in the overall phase, a 34.9 percent (n=22/63) complete response was observed in the EMEND regimen compared to 13.0 percent (n=9/69) in the control regimen.
The most common adverse reactions reported in pooled studies of 352 pediatric patients receiving HEC or MEC treated with the EMEND regimen (versus the control regimen) were neutropenia (13% vs 11%), headache (9% vs 5%), diarrhea (6% vs 5%), decreased appetite (5% vs 4%), cough (5% vs 3%), fatigue (5% vs 2%), hemoglobin decreased (5% vs 4%), dizziness (5% vs 1%), and hiccups (4% vs 1%).
“The FDA approval of this expanded indication for EMEND is the result of our commitment to fully realizing the potential of our therapies to help as many patients as possible,” said Stuart Green, vice president, clinical research, Merck Research Laboratories. “Historically, significant improvements in pediatric medicine have been slow due to many challenges such as clinical trial size. However, at Merck, these obstacles have invigorated our efforts to bring forward a new option for these patients.”
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