Cubist Submits ENTEREG Supplemental NDA
December 21, 2012
LEXINGTON, Mass.--(BUSINESS WIRE)--Cubist Pharmaceuticals, Inc. (NASDAQ: CBST) today announced that it has submitted a supplemental new drug application (sNDA) to the U.S. Food and Drug Administration (FDA) requesting approval for the use of ENTEREG® (alvimopan) to accelerate GI recovery following any surgery that includes a bowel resection with primary anastomosis; expanded from the current indication in patients requiring surgery for colorectal disease.
This proposed label modification is derived from a recently completed randomized, double-blind, placebo-controlled, Phase 4 clinical trial of patients undergoing radical cystectomy for bladder cancer, an extensive surgical procedure that includes resecting a segment of bowel to reconstruct the lower urinary tract. This study, in conjunction with the original clinical trial data, forms the body of evidence supporting the request for expansion of the current indication.
"Delayed GI recovery is one of the most common causes for prolonging hospital stay in patients undergoing surgeries that include a bowel resection," said Cubist's Chief Scientific Officer Steve Gilman, PhD. "This submission is an important achievement for Cubist and we look forward to working with the FDA as they evaluate this application."
Radical Cystectomy Phase 4 Study Design and Key Findings
The radical cystectomy study, a post-approval commitment with the FDA, investigated ENTEREG 12mg or placebo administered by mouth once preoperatively and twice daily (BID) postoperatively for a maximum of 15 hospital doses in 280 patients undergoing radical cystectomy. Assessments for efficacy were performed over a 10-day observation period and safety was evaluated through a 30-day period after the last dose of the study drug.
For the primary endpoint, ENTEREG accelerated upper and lower GI recovery compared to placebo (hazard ratio=1.8, p<0.0001). The mean and median time to achieve GI recovery was 1.3 days and 1.2 days earlier, respectively, in patients receiving ENTEREG compared to placebo. The mean and median postoperative hospital length of stay for patients receiving ENTEREG was 2.6 and 1.0 days shorter, respectively, compared to patients receiving placebo (p=0.005).
The most frequently reported treatment-emergent adverse events in the trial were hypokalemia, anemia, and postoperative ileus. The rate of postoperative ileus was 19.3% higher in the placebo-treated group compared to the ENTEREG-treated group. The incidence of all other treatment-emergent adverse events was comparable between the two groups. The majority of treatment-emergent adverse events were mild or moderate in severity. The incidence of severe treatment-emergent adverse events was comparable between the two treatment groups. In this study, blinded cardiovascular adverse events were adjudicated by an external independent clinical committee. The incidence of cardiovascular events was 15.3% percent for placebo-treated patients and 8.4% for ENTEREG treated patients, which was not statistically different (p=0.09).
ENTEREG was approved in the United States in 2008. It is a peripherally acting µ-opioid receptor antagonist indicated to accelerate the time to upper and lower gastrointestinal recovery following partial large or small bowel resection surgery with primary anastomosis. Because of concerns that long-term use of alvimopan may be associated with an increased risk of myocardial infarction, ENTEREG is available only for short-term (15 doses) use in hospitalized patients. Only hospitals that have registered in and met all of the requirements for the ENTEREG Access Support and Education (E.A.S.E.) program may use ENTEREG. ENTEREG Capsules are contraindicated in patients who have taken therapeutic doses of opioids for more than 7 consecutive days immediately prior to taking ENTEREG, and ENTEREG should be administered with caution to patients receiving more than 3 doses of an opioid within the week prior to surgery. ENTEREG is not recommended for use in patients with severe hepatic impairment, end-stage renal disease, or in patients undergoing surgery for correction of complete bowel obstruction. The most common adverse reactions in patients treated with ENTEREG (incidence ≥3% with ENTEREG and at least 1% greater than placebo) undergoing bowel resection were anemia, dyspepsia, hypokalemia, back pain, and urinary retention. For more information on ENTEREG, including its full prescribing information, the Boxed Warning regarding short-term hospital use and the E.A.S.E.® Program, visit www.ENTEREG.com.
Cubist Pharmaceuticals, Inc. is a biopharmaceutical company focused on the research, development, and commercialization of pharmaceutical products that address significant unmet medical needs in the acute care environment. Cubist is headquartered in Lexington, Mass. Additional information can be found at Cubist's web site at www.cubist.com.
Cubist Pharmaceuticals, Inc.
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