Filed by Sanofi-Synthelabo
Pursuant to Rule 165 and Rule 425(a) under the
United States Securities Act of 1933,
as amended
Subject Company: Aventis
Commission File No. 001-10378
Date: June 4, 2004
On June 4, 2004, Sanofi-Synthelabo issued the following press release.
In connection with the proposed acquisition of Aventis,
Sanofi-Synthelabo has filed with the United States Securities and Exchange
Commission (SEC), a registration statement on Form F-4 (File no: 333-112314),
which includes a prospectus and a prospectus supplement relating to the revised
offer, and related exchange offer materials, to register the Sanofi-Synthelabo
ordinary shares (including Sanofi-Synthelabo ordinary shares represented by
Sanofi-Synthelabo ADSs) to be issued in exchange for Aventis ordinary shares
held by holders located in the United States and for Aventis ADSs held by
holders wherever located and has also filed with the SEC a Statement on Schedule
TO. INVESTORS AND HOLDERS OF AVENTIS SECURITIES ARE STRONGLY ADVISED TO READ THE
REGISTRATION STATEMENT AND THE PROSPECTUS AND PROSPECTUS SUPPLEMENT RELATING TO
THE REVISED OFFER, THE STATEMENT ON SCHEDULE TO, AND ANY OTHER RELEVANT
DOCUMENTS FILED WITH THE SEC, AS WELL AS ANY AMENDMENTS AND SUPPLEMENTS BECAUSE
THEY CONTAIN IMPORTANT INFORMATION. Investors and holders of Aventis securities
may obtain free copies of the registration statement, the prospectus, the
prospectus supplement relating to the revised offer and related exchange offer
materials, and the Statement on Schedule TO, as well as other relevant documents
filed with the SEC, at the SEC's web site at www.sec.gov. The prospectus, the
prospectus supplement relating to the revised offer and other
transaction-related documents are being mailed to Aventis securityholders
eligible to participate in the U.S. offer and additional copies may be obtained
for free from MacKenzie Partners, Inc., the information agent for the U.S.
offer, at the following address: 105, Madison Avenue, New York, New York 10016;
telephone 1-(212) 929-5500 (call collect) or 1-(800) 322-2885 (toll-free call);
e-mail proxy@mackenziepartners.com.
* * * *
[SANOFI-SYNTHELABO LOGO]
[GRAPHIC] INVESTOR RELATIONS
Paris, June 4, 2004
NEW INDICATIONS FOR ARIXTRA(R) IN THE UNITED STATES:
THE TREATMENT OF ACUTE DEEP VENOUS THROMBOSIS
AND ACUTE PULMONARY EMBOLISM.
Sanofi-Synthelabo announced today that the synthetic, selective factor Xa
inhibitor Arixtra(R) (fondaparinux sodium) has been approved by the US Food and
Drug Administration (FDA) for two new indications:
O THE TREATMENT OF ACUTE DEEP VENOUS THROMBOSIS WHEN ADMINISTERED IN
CONJUNCTION WITH WARFARIN SODIUM, AND
O THE TREATMENT OF ACUTE PULMONARY EMBOLISM WHEN ADMINISTERED IN CONJUNCTION
WITH WARFARIN SODIUM WHEN INITIAL THERAPY IS ADMINISTERED IN THE HOSPITAL.
Arixtra(R) is already indicated in the United-States for the prophylaxis of deep
vein thrombosis, which may lead to pulmonary embolism in patients undergoing hip
fracture surgery, including extended prophylaxis, hip replacement surgery and
knee replacement surgery.
The file for the new indications for Arixtra(R) was submitted to the FDA July
31, 2003. The clinical dossier was based upon the findings of the MATISSE PE and
MATISSE DVT studies which demonstrated that a new strength of Arixtra(R) 7.5 mg*
given as a once daily subcutaneous injection, when administered in conjunction
with warfarin sodium, can effectively and safely treat the acute phases of both
deep vein thrombosis and pulmonary embolism.
Arixtra(R) is the first antithrombotic agent to be registered in the US
specifically for the treatment of acute PE since the introduction of
unfractionated heparin (UFH).
The MATISSE PE study is the largest worldwide trial ever performed in the
treatment of pulmonary embolism. This open label trial involved 2,213 patients
with symptomatic PE enrolled in 214 centres in 20 countries worldwide, including
67 centres in the US. The study showed that a fixed once daily subcutaneous dose
of Arixtra(R) 7.5mg*, without need for coagulation monitoring, appears to be at
least as effective and as safe as continuous intravenous and dose-adjusted UFH.
Moreover, in the study, 15% of patients, (26.4% in the US**), received
Arixtra(R) on an outpatient basis, after receiving the first dose in the
hospital, compared to none with UFH.
The MATISSE DVT trial involved 2,205 patients in 23 countries in a total of 154
centers around the world with symptomatic DVT without symptomatic PE. The study
showed that Arixtra(R) 7.5mg*, given once daily in a fixed subcutaneous dose
appears to be at least as effective and safe as dose-adjusted low molecular
weight heparin (LMWH) administered subcutaneously twice a day.
DVT and PE represent two manifestations of the same disease known as Venous
Thromboembolism (VTE), a condition in which blood clots in the lower limbs (DVT)
may travel to the lungs where they can cause a PE. VTE is the third most common
cardiovascular disease after heart attack and stroke. VTE affects about two
million Americans annually, at least 60,000 of whom will die of PE. VTE
represents an annual cost of at least $2.9 billion in the US alone.
As with other antithrombotics, the most common side effect during Arixtra(R)
administration is bleeding. Arixtra(R) is contraindicated in patients with
severely impaired kidney function. Arixtra(R) prophylactic therapy is
contraindicated in patients who weigh less than 50 kg (110 pounds), undergoing
hip fracture, hip replacement and knee replacement surgery because they may have
an increased risk for major bleeding. Patients greater than 75 years of age also
may be more likely to experience major bleeding complications. As with other
antithrombotics, labeling for Arixtra(R) includes a Boxed Warning regarding
possible spinal/epidural haematomas when spinal anaesthesia or spinal puncture
is used.
Arixtra(R) was launched in the United States on February 8, 2002, and in Europe
as from March 27, 2002.
On April 13, 2004, Sanofi-Synthelabo signed an agreement with GlaxoSmithKline
Group (GSK) regarding the divestment by Sanofi-Synthelabo, on a worldwide basis,
of Arixtra(R), Fraxiparine(R) and related assets including the manufacturing
facility located in Notre-Dame de Bondeville, France. The deal is conditional on
completion of Sanofi-Synthelabo's offer for Aventis.
*5mg in patients with a body weight <50kg; 10mg in patients with a body
weight >100 kg
**data on file
In accordance with article 7 of the COB rule no. 2002-04, this press release was
transmitted to the Autorite des marches financiers (AMF) before its publication.
FORWARD-LOOKING STATEMENTS
--------------------------
This press release contains statements that constitute forward-looking
statements within the meaning of the U.S. Private Securities Litigation Reform
Act of 1995. Forward-Looking statements are statements that are not historical
facts. These statements include financial projections and estimates and their
underlying assumptions, statements regarding plans, objectives and expectations
with respect to future operations, products and services, and statements
regarding future performance. Forward-looking statements are generally
identified by the words "expect," "anticipates," "believes," "intends,"
"estimates" and similar expressions. Although Sanofi-Synthelabo's management
believes that the expectations reflected in such forward-looking statements are
reasonable, investors are cautioned that forward-looking information and
statements are subject to various risks and uncertainties, many of which are
difficult to predict and generally beyond the control of Sanofi-Synthelabo, that
could cause actual results and developments to differ materially from those
expressed in, or implied or projected by, the forward-looking information and
statements. The following factors, among other risks and uncertainties that are
described in our
Form 20-F as filed with the SEC on April 2, 2004 and in the Reference Document
filed with the French Autorite des Marches Financiers on April 2, 2004, could
cause actual results to differ materially from those described in the
forward-looking statements: the ability of Sanofi-Synthelabo to expand its
presence profitably in the United States; the success of Sanofi-Synthelabo's
research and development programs; the ability of Sanofi-Synthelabo to protect
its intellectual property rights; and the risks associated with reimbursement of
health care costs and pricing reforms, particularly in the United States and
Europe. Other than as requested by applicable law, Sanofi-Synthelabo does not
undertake any obligation to provide updates or to revise any forward-looking
statements.
IMPORTANT INFORMATION: In connection with the proposed acquisition of Aventis,
Sanofi-Synthelabo has filed a registration statement on Form F-4 (File no.
333-112314), including a prospectus and a prospectus supplement relating to the
revised offer, and will file additional documents with the SEC. INVESTORS ARE
URGED TO READ THE REGISTRATION STATEMENT, INCLUDING THE PROSPECTUS AND THE
PROSPECTUS SUPPLEMENT RELATING TO THE REVISED OFFER, AND ANY OTHER RELEVANT
DOCUMENTS FILED WITH THE SEC, INCLUDING ALL AMENDMENTS AND SUPPLEMENTS, BECAUSE
THEY CONTAIN IMPORTANT INFORMATION. Free copies of the registration statement,
as well as other relevant documents filed with the SEC, may be obtained at the
SEC's web site at www.sec.gov. The prospectus and the prospectus supplement
relating to the revised offer and other transaction-related documents are being
mailed to Aventis security holders eligible to participate in the U.S. offer and
additional copies may be obtained for free from MacKenzie Partners, Inc., the
information agent for the U.S. offer, at the following address: 105, Madison
Avenue, New York, New York 10016; telephone: 1-(212) 929-5500 (call collect) or
1-(800) 322-2885 (toll-free call); e-mail proxy@mackenziepartners.com.
In France, holders of Aventis securities are requested, with respect to the
offer, to refer to the prospectus supplement (note d'information
complementaire), which has been granted visa number 04-384 by the Autorite des
marches financiers ("AMF") and which is available on the website of the AMF
(www.amf-france.org) and without cost from: BNP Paribas Securities Services,
GIS-Emetteurs, Service Logistique, Les Collines de l'Arche, 75450 Paris Cedex 9
and to the recommendation statement (note d'information en reponse) which has
been granted visa number 04-510.
The public offer to holders of Aventis ordinary shares located in Germany (the
"German Offer") is being made in accordance with applicable German law and
pursuant to an offer document/sales prospectus, which is available free of
charge at BNP Paribas Securities Services, Gruneburgweg 14, D-60322 Frankfurt am
Main (Fax: 069 - 152 05 277) and on the website of the Company
(www.sanofi-synthelabo.com). Any decision to tender Aventis ordinary shares in
exchange for Sanofi-Synthelabo ordinary shares under the German Offer must be
taken exclusively with regard to the terms and conditions of the German Offer,
as well as with regard to the information included in the offer document/sales
prospectus, including any amendments thereto, issued in Germany.
The French Offer, the U.S. Offer and the German Offer are being made on
substantially the same terms and completion of these offers is subject to the
same conditions. It is intended that the three offers will expire at the same
time.
Investors and security holders may obtain a free copy of the Form 20-F filed
with the SEC on April 2, 2004 and any other documents filed by Sanofi-Synthelabo
with the SEC at www.sec.gov as well as of the Reference Document filed with the
AMF on April 2, 2004 (No. 04-0391) at www.amf-france.org or directly from
Sanofi-Synthelabo on our web site at: www.sanofi-synthelabo.com.
INVESTOR RELATIONS DEPARTMENT
Philippe Goupit Director of Investor Relations
Arnaud Delepine Investor of Relations Europe
Sanjay Gupta Investor Relations US
Anne d'Halluin-Sulzer Investor Relations
CONTACTS:
E-mail: investor-relations@sanofi-synthelabo.com
EUROPE US
Tel: + 33 1 53 77 45 45 Tel: + 1 212 551 4293
Fax: + 33 1 53 77 42 96 Fax: + 1 212 551 4992