FDA Approves Emend for the Prevention of Postoperative Nausea and Vomiting

First New Class of Postoperative Nausea and Vomiting Therapy in More Than 10 Years

WHITEHOUSE STATION, N.J., July 11, 2006 - Merck & Co., Inc. announced today that the U.S. Food and Drug Administration (FDA) has approved Emend (aprepitant) for the prevention of postoperative nausea and vomiting (PONV), one of the most common side effects associated with surgical procedures. The recommended dose of Emend for PONV is a single, oral 40 mg dose administered within three hours prior to the induction of anesthesia.

Emend belongs to a class of medications called substance P/neurokinin 1 (NK-1) receptor antagonists and is believed to work through a novel mechanism, which primarily blocks nausea and vomiting signals to the brain. This novel mechanism is distinct from how current anti-vomiting therapies work, including 5-HT3 receptor antagonists (Zofran). The 5-HT3 receptor antagonists primarily target nausea and vomiting signals in the gut. Emend represents the first new class of therapy for the management of PONV in more than 10 years.

"Despite use of preventative medications, nearly a third of my patients suffer from postoperative nausea and vomiting. Most episodes of PONV occur after patients leave the postanesthesia care unit, even up to 48 hours after surgery," said Dr. Tong J. Gan, professor of anesthesiology, Department of Anesthesiology, Duke University Medical Center, Durham, NC. "The FDA approval of Emend for PONV now provides physicians with a new option to help prevent post-operative nausea and vomiting."

The FDA approval for Emend is based on two multicenter, randomized, double-blind, active comparator-controlled, parallel-group studies of 1,658 patients undergoing open abdominal surgery. Patients were randomized to receive Emend 40 mg one to three hours before anesthesia or Zofran (ondansetron hydrochloride) 4 mg given intravenously immediately before anesthesia. A single 125 mg dose of Emend was also studied; however, no additional clinical benefit was seen as compared to the 40 mg dose. Of the patients receiving Emend 40 mg, 92 percent were women and eight percent were men, and the age of patients in the group ranged from 19-84 years with a mean age of 46 years.

Emend 40 mg was superior to Zofran 4 mg IV in preventing vomiting through 24 hours following surgery
In study one, (N=573), Emend 40 mg was superior to Zofran 4 mg IV for the prevention of vomiting (emesis) from 0 to 24 hours following surgery. Prevention of vomiting was defined as no emetic episodes and was one of two primary endpoints in the study. Of patients taking Emend 40 mg, 84 percent of patients (246 out of 293) did not experience vomiting through 24 hours compared to 71 percent of patients taking Zofran 4 mg IV (200 out of 280, p<0.001).

Patients taking Emend 40 mg achieved a complete response comparable to Zofran 4 mg IV
In a pre-specified non-inferiority analysis in study one, patients taking Emend 40 mg had a complete response in the 0 to 24 hours following surgery comparable to Zofran 4 mg IV. Complete response was defined as no emetic episodes and no use of rescue therapy, and was the other primary endpoint in the study. In this analysis, 64 percent of patients (187 out of 293) taking Emend 40 mg had a complete response compared to 55 percent of patients (154 out of 280) taking Zofran 4 mg IV. Complete response in the 24 hours following surgery was also evaluated based on a pre-specified superiority analysis in this study, which found that Emend was not superior to Zofran on this endpoint.

Study two (N=494) did not satisfy its primary hypothesis that Emend 40 mg is superior to Zofran 4 mg IV in the prevention of postoperative nausea and vomiting as measured by the proportion of patients with a complete response in the 24 hours following the end of surgery. In the second study, Emend 40 mg demonstrated a clinically meaningful effect with respect to the secondary endpoint of "no vomiting" during the first 24 hours after surgery. Emend 40 mg was associated with a 16 percent improvement over Zofran 4 mg IV in the prevention of vomiting.

Emend 40 mg was superior to Zofran 4 mg IV in preventing vomiting through 48 hours following surgery
Also, in study one Emend 40 mg was superior to Zofran 4 mg IV in the prevention of vomiting from 0 to 48 hours following surgery, a secondary endpoint. Of patients taking Emend 40 mg, 82 percent of patients (238 out of 292) did not experience vomiting through 48 hours compared to 66 percent of patients taking Zofran 4 mg IV (185 out of 279, p<0.001). Stated differently, in this study almost twice as many patients taking Zofran 4 mg IV experienced vomiting (34 percent, or 94 out of 279 patients) as compared to patients taking Emend 40 mg (18 percent, or 54 out of 292 patients) in the 48 hours following surgery.

Emend was generally well tolerated
In these two well-controlled clinical studies, 564 patients received Emend 40 mg orally and 538 patients received Zofran 4 mg IV. Emend was generally well tolerated. Clinical adverse experiences were reported in approximately 60 percent of patients treated with Emend compared to roughly 64 percent of people receiving Zofran. The most common adverse events reported with Emend in the PONV studies vs. Zofran, respectively, were constipation (8.5 percent vs. 7.6 percent), nausea (8.5 percent vs. 8.6 percent), itching (7.6 percent vs. 8.4 percent), fever (5.9 percent vs. 10.6 percent), low blood pressure (5.7 percent vs. 4.6 percent), headache (5.0 percent vs. 6.5 percent) and slow heart rate (4.4 percent vs. 3.9 percent).

"Nausea and vomiting after surgery remains a significant problem, despite the number of different antiemetics on the market," said Robert McMahon, general manager, U.S. Human Health, Merck & Co., Inc. "Emend offers a new and different approach to help reduce the incidence of nausea and vomiting."

Important information about Emend

Emend is only used to help prevent nausea and vomiting following surgery or, when used in combination with other antiemetics, it is used to help prevent nausea and vomiting caused by chemotherapy. It is not used to get rid of nausea and vomiting after they start.

Patients should tell their doctor about all of the medicines they are taking, if they are pregnant or plan to become pregnant, or if they have liver problems. Patients should not take Emend with Orap (pimozide), Seldane (terfenadine), Hismanal (astemizole), or Propulsid (cisapride) as Emend may cause serious or life-threatening problems if taken with these medicines. Emend may also affect some medicines, causing them to work differently in your body. Chronic continuous use of Emend for prevention of nausea and vomiting is not recommended because it has not been studied and because chronic continuous use of Emend may cause some medicines to work differently in the body. Women who use birth control medicines during treatment with Emend, and for up to one month after using Emend, should also use a back-up method of contraception to avoid pregnancy.

About PONV

PONV is one of the most common side effects associated with surgical procedures. Studies show that nausea and vomiting may affect up to 30 percent of all patients undergoing surgery, and as many as 70 percent of high risk patients. One study shows that nearly 80 percent of PONV occurs within 48 hours after surgery. A study has also shown that patients find vomiting to be the most undesirable consequence of surgery, even ranking above surgical pain.

Source: Merck & Co., Inc.

Posted: July 2006


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