Cubist Submits ENTEREG Supplemental NDA

  Cubist Submits ENTEREG Supplemental NDA

Business Wire

LEXINGTON, Mass. -- December 21, 2012

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

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

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

About Cubist
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


Cubist Pharmaceuticals, Inc.
Eileen C. McIntyre, 781-860-8533
Senior Director, Investor Relations
Francis McLoughlin, 781-860-8777
Director, Corporate Communications
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