Santarus Announces Publication of Results from UCERIS Pivotal Study in Gastroenterology

Update: Uceris (budesonide) Now FDA Approved - January 14, 2013

UCERIS 9 mg statistically more effective than placebo for inducing remission in patients with active, mild to moderate ulcerative colitis

SAN DIEGO--(BUSINESS WIRE)--Sep 27, 2012 - Santarus, Inc. (NASDAQ: SNTS) today announced that results from its CORE I clinical study, one of two of the company's pivotal Phase III clinical studies with UCERIS (budesonide) in ulcerative colitis, have been published online in the journal Gastroenterology. The article titled, Once-Daily Budesonide MMX® Extended-Release Tablets Induce Remission in Patients with Mild to Moderate Ulcerative Colitis – Results from the CORE I Study can be found online at www.gastrojournal.org.

The results from CORE I indicate that the investigational drug UCERIS 9 mg had a statistically significant benefit over placebo in the primary endpoint of combined clinical and endoscopic remission at week 8 among patients with active, mild to moderate ulcerative colitis. The U.S. Food and Drug Administration (FDA) is currently reviewing the company's New Drug Application (NDA) for UCERIS for the induction of remission in patients with active, mild to moderate ulcerative colitis with a target action date of January 16, 2013.

The percentage of patients achieving the primary endpoint of combined clinical and endoscopic remission at week 8 in the UCERIS 9 mg group was significantly greater than that seen in the placebo group (17.9% vs. 7.4%, p= 0.0143; odds ratio (OR): 2.71). The combined clinical and endoscopic remission rate for UCERIS 6 mg (13.2% vs 7.4%, p= 0.1393; OR: 1.90) and for the reference drug Asacol® (mesalamine) 2.4 g (12.1% vs 7.4%, p= 0.2200; OR: 1.71) were numerically greater than placebo, but the differences were not statistically significant. These results are summarized in the table below.

 

 

      Placebo

n= 121

 

    Uceris 9 mg

n= 123

 

    Uceris 6 mg

n= 121

 

    Asacol 2.4 g

n= 124

 

Combined Clinical and Endoscopic Remission, %       7.4%     17.9%     13.2%     12.1%
P-value             0.0143*     0.1393     0.2200
Odds ratio             2.71     1.90     1.71
*Statistically significant (p < 0.025)

Efficacy analyses were done in the modified intent to treat population under a prespecified statistical analysis plan, which included all randomized patients who received at least one dose of a study drug and excluded patients with major good clinical practice or entry criteria violations and those with normal histology at baseline as determined by central histopathology review.

“In this study, UCERIS 9 mg was well tolerated, and significantly more effective than placebo in inducing remission in patients with active, mild to moderate ulcerative colitis,” said William J. Sandborn, M.D., Chief, Division of Gastroenterology, Director, University of California San Diego (UCSD) IBD Center, Professor of Clinical Medicine, UCSD Health System and lead author of the Gastroenterology article. “These results suggest that UCERIS could provide an important addition to the therapeutic landscape for clinicians who manage patients with mild to moderate ulcerative colitis.”

UCERIS 9 mg and 6 mg were generally well tolerated and the frequency of treatment emergent adverse events was similar to placebo. The most frequent treatment emergent adverse events (experienced by ‰¥ 5.0% of patients in any treatment group) were worsening ulcerative colitis, headache, pyrexia, insomnia, back pain, nausea, abdominal pain, diarrhea and flatulence. Potential glucocorticoid effects occurred in similar percentages of patients across all treatment groups. Potential glucocorticoid effects were observed in 10.1% of patients in the placebo group, 11.8% of patients in the UCERIS 9 mg group, 5.6% of patients in the UCERIS 6 mg group and 7.9% of patients in the Asacol group.

Phase III Study (CORE* I and II) Design

*COlonic RElease budesonide for the treatment of mild to moderate ulcerative colitis

UCERIS was evaluated for the treatment of active, mild to moderate ulcerative colitis in two multicenter, randomized, double-blind, double-dummy, placebo-controlled four-arm Phase III clinical studies. The primary endpoint was the induction of combined clinical and endoscopic remission, defined as an overall UCDAI score ‰¤ 1 after 8 weeks of treatment with subscores of 0 for both rectal bleeding and stool frequency, a normal colonic mucosa without any sign of friability, and ‰¥ 1 point reduction from baseline in the endoscopic score.

 

  • CORE I was conducted in North America and India and compared UCERIS 9 mg or 6 mg dosed once daily to placebo. The study included a reference arm utilizing a dose of two Asacol (mesalamine) 400 mg delayed-release tablets dosed three times a day resulting in a total of 2.4 grams daily. The trial enrolled a total of 509 patients.
  • CORE II was conducted in Europe, Australia, Israel, and Russia and compared UCERIS 9 mg or 6 mg dosed once daily to placebo. The study included a reference arm that utilized a dose of three Entocort® EC 3 mg capsules resulting in a once daily dose of 9 mg. The trial enrolled a total of 511 patients.

The CORE I and CORE II clinical studies were powered to show a statistical difference between the two UCERIS treatment arms and placebo. The trials were not powered to show statistical differences between UCERIS and the reference arms (Asacol in the CORE I study and Entocort EC in CORE II).

About UCERIS (budesonide)

UCERIS is an investigational drug that contains budesonide, a corticosteroid, in a novel oral tablet formulation that utilizes proprietary MMX® multi-matrix system technology, which is designed to result in the controlled release and distribution of budesonide throughout the length of the colon. UCERIS is being developed in collaboration with Cosmo Technologies Limited, a subsidiary of Cosmo Pharmaceuticals S.p.A.

About Ulcerative Colitis

Ulcerative colitis is a form of inflammatory bowel disease (IBD) that produces inflammation and ulcers along the inside of the colon. The inflammation can interfere with the normal function of the colon, often causing cramping, bloating, diarrhea, bleeding, fatigue, weight loss and frequent bowel movements. It is believed that as many as 700,000 people in the U.S. suffer from ulcerative colitis.

About Santarus

Santarus, Inc. is a specialty biopharmaceutical company focused on acquiring, developing and commercializing proprietary products that address the needs of patients treated by physician specialists. The company's current commercial efforts are focused on GLUMETZA® (metformin hydrochloride extended release tablets) and CYCLOSET® (bromocriptine mesylate) tablets, which are indicated as adjuncts to diet and exercise to improve glycemic control in adults with type 2 diabetes, and on FENOGLIDE® (fenofibrate) tablets, which is indicated as an adjunct to diet to reduce high cholesterol.

Santarus has a diverse product development pipeline. A New Drug Application for UCERIS (budesonide) tablets for induction of remission of active, mild to moderate ulcerative colitis is under review by the U.S. Food and Drug Administration with a response expected in January 2013. The pipeline also includes two late-stage investigational drugs in Phase III clinical studies: RUCONEST® (recombinant human C1 esterase inhibitor) for treatment of acute attacks of hereditary angioedema and rifamycin SV MMX® for treatment of travelers' diarrhea. In addition, the company's investigational monoclonal antibody, SAN-300, is being evaluated in a Phase I clinical program. More information about Santarus is available at www.santarus.com.

Santarus cautions you that statements included in this press release that are not a description of historical facts are forward-looking statements. The inclusion of forward-looking statements should not be regarded as a representation by Santarus that any of its plans or objectives will be achieved. Actual results may differ materially from those set forth in this release due to the risks and uncertainties inherent in Santarus' business, including, without limitation: whether Santarus obtains regulatory approval for UCERIS in a timely manner or at all, including whether the FDA agrees with the statistical analysis plan for the UCERIS Phase III studies, the clinical interpretation of the results and the conduct of the studies; whether the FDA requires completion of additional clinical studies or other development programs before approving UCERIS; whether the planned Phase IIIb clinical study will be completed in a timely manner with a positive outcome; risks associated with the collaboration with Cosmo relating to the MMX product candidates, including the potential for termination of the collaboration; competition from other products; unexpected adverse side effects or inadequate therapeutic efficacy of Santarus' products and product candidates; the scope and validity of patent protection for Santarus' products and product candidates; and other difficulties or delays relating to the development, testing, manufacturing and marketing of, and obtaining and maintaining regulatory approvals for, Santarus' products and product candidates; and other risks detailed in Santarus' prior press releases as well as in prior public periodic filings with the Securities and Exchange Commission.

You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof. All forward-looking statements are qualified in their entirety by this cautionary statement and Santarus undertakes no obligation to revise or update this news release to reflect events or circumstances after the date hereof. This caution is made under the safe harbor provisions of Section 21E of the Private Securities Litigation Reform Act of 1995.

Santarus®, FENOGLIDE® and UCERIS are trademarks of Santarus, Inc. GLUMETZA® is a trademark of Biovail Laboratories International S.r.l. licensed exclusively in the United States to Depomed, Inc. CYCLOSET® is a trademark of VeroScience LLC. MMX® is a trademark of Cosmo Technologies Limited.

RUCONEST® is a trademark of Pharming Group N.V.

Contact: COMPANY CONTACT:
Santarus, Inc.
Martha L. Hough
VP Finance & Investor Relations
858-314-5824
or
Debra P. Crawford
Chief Financial Officer
858-314-5708
or
INVESTOR CONTACT:
Westwicke Partners, LLC
Stefan Loren, Ph.D.
858-356-5930
sloren@westwicke.com
or
Robert Uhl
858-356-5932
robert.uhl@westwicke.com

 

Posted: September 2012

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