LAINATE (November 8, 2010) Cosmo Pharmaceuticals S.p.A. (SIX: COPN) today announced positive top-line results from the second pivotal Phase III clinical study which was conducted in the EU to evaluate the safety and efficacy of budesonide MMX® for the induction of remission of mild or moderate ulcerative colitis. The study results show that budesonide MMX 9 mg taken once daily met the primary endpoint of superiority to placebo (p=0.0047) in achieving clinical remission as measured by the ulcerative colitis disease activity index (UCDAI) score after eight weeks of treatment. Cosmo Technologies Ltd., a subsidiary of Cosmo Pharmaceuticals, and Santarus Inc. (NASDAQ: SNTS), are collaborating on the entire budesonide MMX Phase III clinical program. In late September, Cosmo Pharmaceuticals and Santarus announced positive top-line results from the Phase III clinical study of budesonide MMX in North America and in India.
Mauro Ajani, Chief Executive Officer of Cosmo Pharmaceuticals, said, “We have now completed the second successful pivotal Phase III trial as required by the regulatory agencies. We now plan to file the MAA with the Dutch Regulatory Agency in the first half of 2011. Santarus, our U.S. partner, plans to submit an NDA to the FDA in the second half of 2011 following the completion of an ongoing double-blind, placebo-controlled extended use study. Around 1.7 million people in the US and Europe suffer with this disorder. I am pleased that, with these results, we are closer to providing a better treatment option. This again demonstrates the versatility of the MMX technology and its potential application in further programs.”
Under the statistical analysis plan submitted to the regulatory agencies for each Phase III study, to achieve statistical significance the budesonide MMX 9 mg and 6 mg treatment arms required a separate analysis at a p-value of 0.025 compared with the placebo group. The intent-to-treat (ITT) population in the pre-defined statistical analysis plan was all randomized patients who received at least one dose of a study drug, excluding patients with normal histology at baseline as determined by biopsy, or due to Good Clinical Practice (GCP) violations or major entry criteria violations.
Based on the preliminary analysis, remission rates for the ITT drug treatment groups versus placebo are summarized in the table below:
Treatment Arm Number of
Patients Patients in Remission (%)
Budesonide MMX 9 mg 109 19 (17.4%) 0.0047*
Budesonide MMX 6 mg 109 9 (8.3%) 0.2876
Entocort® EC (budesonide) reference arm(a) 103 13 (12.6%) 0.0481**
Placebo 89 4 (4.5%)
*Statistically significant vs placebo at p=0.025
** Statistically significant vs placebo at p=0.05
(a)Not powered to show a statistical difference between budesonide MMX treatment arms and Entocort
The budesonide MMX 6 mg arm was included in the eight-week induction study at the request of the regulatory agencies to determine the lowest effective dose.
The top-line study results indicate that budesonide MMX 9 mg and 6 mg were generally well tolerated and the frequency of treatment related adverse events was similar across all treatment groups.
Budesonide MMX Phase III Study Design
Budesonide MMX was evaluated for the treatment of mild or moderate active ulcerative colitis in two Phase III clinical studies, both of which are intended to support worldwide regulatory submission (excluding Japan). The primary endpoint was the achievement of clinical remission as measured by a UCDAI score = 1 after eight weeks of treatment with a score of 0 for rectal bleeding and stool frequency, = 1 point reduction from baseline in the endoscopy score and without any sign of mucosal friability (an indicator of mucosal inflammation).
Each clinical study was a multicenter, randomized, double-blind, double-dummy, placebo-controlled four-arm study.
• Study CB-01-02/02 was conducted in Europe, Russia, Israel and Australia and compared budesonide MMX 9 mg or 6 mg dosed once daily to placebo. A reference arm using three Entocort EC 3 mg capsules for a total of 9 mg dosed once daily was also included.
• Study CB-01-02/01 was conducted in North America, mainly the U.S., and India. In this study budesonide MMX 9 mg or 6 mg dosed once daily was compared to placebo. A reference arm using two Asacol 400 mg delayed-release tablets dosed three times a day for a total of 2400 mg daily was also included.
The Phase III clinical studies were powered to show a statistical superiority between the two budesonide MMX treatment arms and placebo. The reference arms using Asacol in the U.S. study and Entocort EC in the European study were agreed with the two regulatory agencies and were not powered to show statistical differences versus the other treatment arms.
Mauro Ajani, CEO, Luigi Moro, CSO, Giuseppe Cipriano COO and Chris Tanner CFO, will host a conference call to be held at 10 a.m. CET today (8 November 2010). To participate please use the dial-in numbers below:
From Europe: +41 (0)91 610 56 00
From UK: +44 (0)203 059 58 62
The conference call will be held in English. Presentation slides are available ahead of the conference call on the website of Cosmo (www.cosmopharma.com).
Cosmo Pharmaceuticals’ Research Day 2010
Cosmo will be hosting a research and development day in Zurich on December 1, 2010. For more information and pre-registrations, please contact Florian Zingg, firstname.lastname@example.org / phone +41 43 244 81 41.
About Budesonide MMX
Budesonide MMX is an investigational drug that is a locally acting corticosteroid in a novel, patented, oral tablet formulation, which utilizes Cosmo’s proprietary MMX® multi-matrix system technology and is designed to result in the controlled release and distribution of budesonide throughout the length of the colon. Budesonide has topical anti-inflammatory activity and due to an extended first pass effect, has less systemic absorption than other corticosteroids.
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, which may also strongly affect quality of life. It is believed that as many as 0.8 million people in the U.S. and as many as 0.9 million people in the EU have Ulcerative Colitis .
Ulcerative colitis is a chronic relapsing-remitting illness for which there is no known cure, but with appropriate treatment patients can manage their symptoms. However, it is estimated that up to 30% of patients with mild or moderate ulcerative colitis do not respond to aminosalicylate (5-ASA) drugs and require a different or add on therapy. Patients refractive to treatment with 5-ASA drugs typically receive a course of a systemically absorbed corticosteroid, the success of which may be limited by significant side effects. For moderate to severe cases of ulcerative colitis, immunosuppressant drugs or biologic drugs may be prescribed. If the condition does not respond to pharmaceutical therapy and the symptoms are severe, the patient may be referred for surgery.
About Cosmo Pharmaceuticals
Cosmo is a speciality pharmaceutical company that aims to become a global leader in optimised therapies for selected gastrointestinal and topically treated skin disorders. The company’s proprietary clinical development pipeline specifically addresses innovative treatments for IBD, such as ulcerative colitis and Crohn’s disease, and colon infections. Cosmo’s first MMX® product that has reached the market is Lialda® / Mezavant® / Mesavancol®, a treatment for IBD that is licensed globally to Giuliani and Shire Limited. Cosmo’s proprietary MMX® technology is at the core of its product pipeline and was developed from its expertise in formulating and manufacturing gastrointestinal drugs for international clients at its GMP (Good Manufacturing Practice) facilities in Lainate, Italy. The technology is designed to deliver active ingredients in a targeted manner in the intestines. More information about Cosmo is available on the company’s website at www.cosmopharma.com.
Dr. Chris Tanner, CFO & Head of Investor Relations
Tel: +39 331 5700 1679
Fax: +39 02 9333 7663
Holborn Gate, 26 Southampton Buildings
London, WC2A 1PB
T +44 (0)20 7269 7125
F +44 (0)20 7242 8695