Sanofi US News

The sanofi-aventis Group announced today the interim results of a large ongoing, open-label study demonstrating that men treated with UroxatralÒ (alfuzosin HCl), a clinically uroselective alpha1-blocker for the treatment of the signs and symptoms of enlarged prostate, or benign prostatic hyperplasia (BPH), reported sustained benefit over two years in reducing lower urinary tract symptoms (LUTS) and sexual function.  Further, a second analysis from the trial demonstrated the relationship between LUTS severity and sexual function and showed that improvement in men with LUTS taking Uroxatral corresponded to similar improvements in sexual function such as stiffness of erection, volume of ejaculate, and degree of pain upon ejaculation.  Both of the above analyses were presented at the 100th Annual Meeting of the American Urological Association (AUA). 

“These results are important because they demonstrate consistent efficacy with Uroxatral for treatment of the signs and symptoms of enlarged prostate,” said Mostafa Elhilali, MD, Professor and Chair, Department of Surgery at McGill University, Montreal, QC.  “These studies reaffirm that Uroxatral provides efficacy over the long-term.” 

Study Results
In one analysis of the Alfone study, an open-label trial conducted outside the United States, men with LUTS symptoms suggestive of BPH reported a 41 percent improvement in their Bother Score, a measure to determine severity of inconvenience of LUTS; a 38.5 percent improvement in their International Prostate Symptom Score (IPSS), a questionnaire that helps doctors to determine the degree or severity of LUTS symptoms in BPH patients; as well as a 30.4 percent improvement in reports of night awakenings for urination (nocturia).  Furthermore, the analysis demonstrated continued improvement in sexual function from baseline after two years, including sexual drive (5.7 percent), erectile function (12.9 percent), ejaculation (5.6 percent), and overall sexual satisfaction (18.4 percent).

In a separate analysis of Alfone, also presented at the AUA meeting, investigators looked at improvement of the IPSS and sexual function categories after one year of UroxatralÒ (alfuzosin HCl) treatment.  In the analysis, men reported a reduction in Bother Score by 33.2 percent, and a reduction in IPSS domains by 32.1 percent compared to baseline.  However, in men with sexual dysfunction, the reported clinical improvements in such categories as stiffness of erection, ejaculation in general and pain or discomfort upon ejaculation all showed more marked improvements in those patients who began the study with more severe LUTS.

Study Design and Safety
The study, called Alfone, is an ongoing, multi-center, non-comparative, observational, open-label study designed to collect, under daily practice conditions, clinical data on the safety profile and efficacy of Uroxatral in over 7,700 patients with LUTS suggestive of BPH.  Patients received Uroxatral 10 mg once-daily and are asked to fill out the IPSS, the DAN-PSSsex, which evaluates reduced erection, reduced ejaculation and painful ejaculation, as well as how bothersome these domains are for the men who experience them, a health-related quality of life scale and the Brief Sexual Function Inventory (BSFI), which evaluates sexual drive, erectile function, ejaculation, problem assessment and overall satisfaction.

In the first analysis, 839 men (mean age 67.3 years) complaining of LUTS suggestive of BPH were assessed after two years.  Investigators analyzed results from the IPSS and the BSFI.  Efficacy results were provided in the intent-to-treat population.  

In this analysis, Uroxatral was well tolerated, and there were no clinically relevant changes in blood pressure, including in elderly and hypertensive patients.  The most common side effect was dizziness (3.0 percent).  Adverse events related to sexual function were uncommon.  

In the second subset analysis, 3,076 men, (mean age 65.9 years) were analyzed after one-year in the Alfone study.  Sexual function was assessed by the DAN-PSSsex.  Analysis was performed in the intent-to-treat population.  

About BPH
BPH is defined as a progressive condition in which prostate cells grow more rapidly than normal and cause the prostate to become enlarged.  BPH is not cancer and affects more than eight million men in the U.S.  In fact, more than half of men over age 60 have the condition and after age 80, men have an 80% chance of developing the condition.  Left untreated, the symptoms may progress, leading to serious health problems including urinary tract infections, bladder and kidney damage, bladder stones, incontinence and acute urinary retention.  

Important Information About Uroxatral 
Uroxatral is an alpha1-blocker indicated for the treatment of the signs and symptoms of benign prostatic hyperplasia or enlarged prostate.

Uroxatral is contraindicated in patients with moderate or severe hepatic insufficiency and therefore should not be used in these patients.  Uroxatral should not be administered with potent CYP3A4 inhibitors and therefore should not be used in combination with drugs such as ketoconazole, itraconazole, or ritonavir.

Postural hypotension with or without symptoms (e.g., dizziness) may develop within a few hours following administration of Uroxatral.  As with all alpha-blockers, there is a potential for syncope. Patients should be warned of the possible occurrence of such events and should avoid situations where injury could result should syncope occur.

Uroxatral should be used with caution in patients with severe renal insufficiency, and should not be prescribed to patients with a known history of QT prolongation or to patients who are taking medication known to prolong QT.

The most common side effects are dizziness, upper respiratory tract infection, headache, and fatigue. For full prescribing information, call 1-800-633-1610 or visit www.uroxatral.com.

Sanofi-aventis Group is the world’s third largest pharmaceutical company, ranking number one in Europe.  Backed by a world-class R&D organization, sanofi-aventis is developing leading positions in seven major therapeutic areas: cardiovascular, thrombosis, oncology, metabolic diseases, central nervous system, internal medicine, and vaccines. sanofi-aventis is listed in Paris (EURONEXT : SAN) and in New York (NYSE : SNY).

Sanofi-aventis, manufacturers of Uroxatral, sponsored the Alfone study.

Forward Looking Statements
This press release contains forward-looking statements as defined in the 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,” “plans” and similar expressions.  Although sanofi-aventis’ 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-aventis, 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.  These risks and uncertainties include those discussed or identified in the public filings with the SEC and the AMF made by sanofi-aventis, including those listed under “Risk 

Factors” and “Cautionary Statement Regarding Forward-Looking Statements” in sanofi-aventis’ annual report on Form 20-F for the year ended December 31, 2004.  Other than as required by applicable law, sanofi-aventis does not undertake any obligation to update or revise any forward-looking information or statements.

The sanofi-aventis Group conducts its business in the United States through its subsidiaries Sanofi-Synthélabo Inc., Aventis Pharmaceuticals Inc. and Sanofi Pasteur Inc.

Christopher Vancheri, 908-243-6776, christopher.vancheri@sanofi-aventis.com 
Marisol Peron, 908-243-7592, marisol.peron@sanofi-aventis.com