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EX-99.1 - EX-99.1 - SANTARUS INC | a57415exv99w1.htm |
UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
SECURITIES AND EXCHANGE COMMISSION
WASHINGTON, DC 20549
FORM 8-K
CURRENT REPORT
Pursuant to Section 13 or 15(d) of the
Securities Exchange Act of 1934
Pursuant to Section 13 or 15(d) of the
Securities Exchange Act of 1934
Date of Report (Date of earliest event reported): September 29, 2010
SANTARUS, INC.
(Exact Name of Registrant as Specified in Its Charter)
Delaware | 0-50651 | 33-0734433 | ||
(State or Other Jurisdiction | (Commission File Number) | (I.R.S. Employer | ||
of Incorporation or Organization) | Identification No.) |
3721 Valley Centre Drive, Suite 400, San Diego, California 92130
(Address of Principal Executive Offices) (Zip Code)
(Address of Principal Executive Offices) (Zip Code)
(858) 314-5700
(Registrants Telephone Number, Including Area Code)
N/A
(Former Name or Former Address, if Changed Since Last Report)
Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy
the filing obligation of the registrant under any of the following provisions:
o | Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425) | |
o | Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12) | |
o | Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b)) | |
o | Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c)) |
Item 8.01 Other Events.
On September 29, 2010, Santarus, Inc. (Santarus or the Company) issued a press release
announcing positive top-line results from the Phase III clinical study conducted in the U.S. and
India to evaluate the safety and efficacy of budesonide MMX® for the induction of
remission of mild or moderate active ulcerative colitis. A copy of the press release is attached
hereto as Exhibit 99.1 and is incorporated herein by reference.
The study results show that budesonide MMX 9 mg taken once daily met the primary endpoint of
superiority to placebo (p=0.0143) in achieving clinical remission as measured by the ulcerative
colitis disease activity index (UCDAI) score after eight weeks of treatment. The top-line study
results also indicate that budesonide MMX 9 mg and 6 mg were generally well tolerated and the
frequency of treatment emergent adverse events was similar to placebo. Santarus and Cosmo
Technologies Ltd., a subsidiary of Cosmo Pharmaceuticals (Cosmo), are collaborating on the
budesonide MMX Phase III clinical program.
Under the statistical analysis plan submitted to the U.S. Food and Drug Administration (FDA)
for the 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:
Patients in | ||||||||||||
Treatment Arm | Number of Patients | Remission (%) | p-value | |||||||||
Budesonide MMX 9 mg |
123 | 22 (17.9 | %) | 0.0143 | * | |||||||
Budesonide MMX 6 mg |
121 | 16 (13.2 | %) | 0.1393 | ||||||||
Asacol®
(mesalamine)
reference arm |
124 | 15 (12.1 | %) | 0.2200 | (a) | |||||||
Placebo |
121 | 9 (7.4 | %) |
* | Statistically significant vs. placebo | |
(a) | Not powered to show a statistical difference between budesonide MMX treatment arms and Asacol |
Remission rates for the treatment groups consisting of per protocol patients versus placebo,
based on the preliminary analysis, are summarized in the table below:
Patients in | ||||||||||||
Treatment Arm | Number of Patients | Remission (%) | p-value | |||||||||
Budesonide MMX 9 mg |
69 | 20 (29.0 | %) | 0.0027 | * | |||||||
Budesonide MMX 6 mg |
72 | 11 (15.3 | %) | 0.2110 | ||||||||
Asacol (mesalamine)
reference arm |
73 | 10 (13.7 | %) | 0.3144 | (a) | |||||||
Placebo |
61 | 5 (8.2 | %) |
* | Statistically significant vs. placebo | |
(a) | Not powered to show a statistical difference between budesonide MMX treatment arms and Asacol |
The per protocol patients treatment groups excluded patients from the intent to treat patient
population who had specified protocol deviations.
Remission rates for the data set consisting of all 509 patients randomized and receiving at
least one dose of study drug versus placebo (with patients who had normal histology at baseline or
GCP violations or major entry criteria violations assigned to the non-responder group), based on
the preliminary analysis, are summarized in the table below:
Patients in | ||||||||||||
Treatment Arm | Number of Patients | Remission (%) | p-value | |||||||||
Budesonide MMX 9 mg |
127 | 22 (17.3 | %) | 0.0119 | * | |||||||
Budesonide MMX 6 mg |
127 | 16 (12.6 | %) | 0.1350 | ||||||||
Asacol (mesalamine)
reference arm |
127 | 15 (11.8 | %) | 0.1912 | (a) | |||||||
Placebo |
128 | 9 ( 7.0 | %) |
* | Statistically significant vs. placebo | |
(a) | Not powered to show a statistical difference between budesonide MMX treatment arms and Asacol |
Treatment emergent adverse events for the safety data set, based on the preliminary analysis,
are summarized in the table below:
Treatment | ||||||||||||||||
Emergent | Mild | Moderate | Severe | |||||||||||||
Treatment Arm | AEs (%) | (%) | (%) | (%) | ||||||||||||
Budesonide MMX 9 mg (n=127) |
57.5 | % | 23.6 | % | 27.6 | % | 6.3 | % | ||||||||
Budesonide MMX 6 mg (n=126) |
58.7 | % | 26.2 | % | 23.0 | % | 9.5 | % | ||||||||
Asacol (mesalamine)
reference arm (n=127) |
63.0 | % | 30.7 | % | 27.6 | % | 4.7 | % | ||||||||
Placebo (n=129) |
62.0 | % | 24.0 | % | 26.4 | % | 11.6 | % |
Santarus believes the ITT population defined in its statistical analysis plan is appropriate,
however, additional sensitivity analyses as described above or otherwise may be performed as part
of the regulatory review process.
European Phase III Clinical Study
Santarus also announced that it expects to have the top-line results from the European Phase
III clinical study available in November 2010. Final audits at the European clinical sites are
being conducted prior to locking and unblinding the database.
Assuming positive results in the European clinical study, Santarus plans to submit a New Drug
Application (NDA) for budesonide MMX 9 mg in the second half of 2011 following the completion of
the ongoing double-blind, placebo-controlled extended use study.
Budesonide MMX Phase III Study Design
Budesonide MMX is being evaluated for the treatment of mild or moderate active ulcerative
colitis in two Phase III clinical studies, both of which are intended to support U.S. regulatory
submission. The primary endpoint is 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,
and > 1 point reduction from baseline in the endoscopy score 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-01-02/01 was conducted in the U.S. and India. In this study budesonide MMX 9 mg or 6 mg dosed once daily were 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 (the FDA-approved dosage of Asacol for induction of remission of ulcerative colitis) was also included. | ||
| Study CB-01-02/02 was conducted in Europe and compared budesonide MMX 9 mg or 6 mg dosed once daily to placebo. A reference arm using three Entocort EC® (budesonide) 3 mg capsules for a total of 9 mg dosed once daily was also included. |
The Phase III clinical studies were powered to show a statistical difference 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 not powered to show statistical differences versus
budesonide MMX.
Extended Use Study Ongoing Through Mid-2011
As previously reported, the FDA requested that the results from an additional 12-month
extended use study be included in the Phase III clinical program to support a U.S. regulatory
submission. This study is designed to:
| Evaluate the long-term safety and tolerability of budesonide MMX 6 mg, and | ||
| Collect data on the efficacy of budesonide MMX 6 mg in the maintenance of remission of ulcerative colitis compared to placebo. |
A total of 123 patients from the Phase III clinical studies in the U.S., India and Europe are
enrolled in this double-blind, placebo-controlled extended use study, which is scheduled to be
completed in mid-2011.
Forward-Looking Statements
Santarus cautions you that statements included in this report that are not a description of
historical facts are forward-looking statements. Forward-looking statements include statements
regarding: the timing of European study results, the completion of the extended use study and the
U.S. NDA submission for budesonide MMX. The inclusion of forward-looking statements should not be
regarded as a representation by Santarus that any plans will be achieved. Actual results may differ
materially from those set forth in this report due to the risks and uncertainties inherent in
Santarus business, including, without limitation: Santarus ability to successfully develop its
budesonide MMX, rifamycin SV MMX and other product candidates in a timely manner or at all
(including timely and successful completion of the budesonide MMX European Phase III and extended
use studies); whether the final audits at clinical sites for the budesonide MMX European Phase III
study are successfully completed; whether Santarus is able to obtain regulatory approval for
budesonide MMX and its other product candidates in a timely manner or at all, including whether the
FDA agrees with the statistical analysis plan for the budesonide MMX Phase III studies and
interpretation of the results; 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 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 report 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.
Item 9.01 Financial Statements and Exhibits.
(d) Exhibits.
99.1 | Press Release, dated September 29, 2010 |
SIGNATURE
Pursuant to the requirements of the Securities Exchange Act of 1934, as amended, the
Registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly
authorized.
SANTARUS, INC. | ||||||
Date: September 29, 2010
|
By: Name: |
/s/ Gerald T. Proehl
|
||||
Title: | President and Chief Executive Officer |
EXHIBIT INDEX
Exhibit No. | Description | |
99.1
|
Press Release, dated September 29, 2010 |