BRIDGEWATER, N.J., Feb. 12 /PRNewswire-FirstCall/ -- In order to give a representation of our underlying economic performance, we present and explain an adjusted(1) income statement. We also report adjusted net income and adjusted EPS (excluding selected items) in U.S. dollars(2) in order to facilitate comparisons with the majority of major pharmaceutical groups. The 2007 consolidated income statement is provided in the Appendices. Full-year consolidated net income for 2007 was euro 5,263 million, against euro 4,006 million for 2006.
2007 full year: euro 5.28 adjusted EPS with selected items; euro 5.17 excluding selected items
2008 guidance
Barring major adverse events, sanofi-aventis expects 2008 adjusted EPS excluding selected items(5) to grow around 7%, calculated at constant 2007 euro/dollar parity (1,371). Sensitivity to the euro/dollar exchange rate is estimated at 0.5% of growth for a 1-cent movement in the exchange rate. (see page 11)
Sanofi-aventis generated fourth-quarter net sales of euro 6,911 million, down 2.2%. Exchange rate movements had an unfavorable effect of 4.2 points, mainly due to the U.S. dollar. Changes in Group structure had a favorable effect of 0.4 of a point, reflecting the consolidation of net sales of Ticlid in Japan from October 1. On a reported basis, net sales fell by 6.0%.
2007 full-year net sales rose by 2.8% to euro 28,052 million. Exchange rate movements had an unfavorable effect of 3.8 points. Changes in Group structure had an unfavorable effect of 0.1 of a point over the year as a whole. After taking account of these effects, net sales fell by 1.1% on a reported basis.
The group net sales consist of sales of pharmaceuticals division (90.1%) and sales of vaccines division (9.9% versus 8.9% in 2006)
Net sales by division - Pharmaceuticals
Fourth-quarter net sales for the pharmaceuticals business were euro 6,262 million, down 0.6%. Net sales of the top 15 products were down 0.3% at euro 4,174 million, representing 66.7% of pharmaceuticals net sales against 66.5% for the comparable period of 2006.
Excluding the impact of the introduction of generics(4) of Ambien(R) IR in the United States and Eloxatin(R) in Europe, the top 15 products would have recorded growth of 9.5%.
Over 2007 as a whole, net sales for the pharmaceuticals business were up 1.7% at euro 25,274 million. Net sales of the top 15 products rose by 3.2% to euro 17,071 million, representing 67.5% of pharmaceuticals net sales against 66.5% in 2006. Excluding the impact of the introduction of generics(4) of Ambien(R) IR in the United States and Eloxatin(R) in Europe, the top 15 products would have recorded growth of 10.7% in 2007.
Fourth-quarter net sales of other pharmaceutical products were down 1.0% at euro 2,088 million. 2007 full-year net sales of other pharmaceutical products were down 1.5% at euro 8,203 million. In the “Other Countries” region, these products reported growth of 4.1% to euro 2,564 million; in Latin America, growth was even stronger at 10.2% (euro 918 million).
Comments by product
Net sales of Lovenox(R), the leading low molecular weight heparin on the market, rose by 17.4% in the quarter to euro 674 million. The product reported strong growth across all three regions: 16.5% in the United States, 15.5% in Europe, and 27.9% in the “Other Countries” region. In the United States, increased use in medical prophylaxis remains the main growth driver.
In January 2008, Lovenox(R) was approved in Japan for the prevention of venous thromboembolism (VTE) in patients undergoing orthopedic surgery of the lower limbs such as total hip replacement, total knee replacement and hip fracture surgery. Further clinical trials are ongoing to extend the product’s indication in Japan to patients undergoing abdominal surgery who are at risk of venous thromboembolism.
Lantus(R) is the first insulin brand in the world to exceed euro 2 billion of sales (euro 2,031 million). In the fourth quarter, the product enjoyed strong growth across all three regions. The new SoloSTAR(R) disposable pen used to administer Lantus(R) is now available in most European countries and in the United States.
Findings presented at the American Heart Association’s 2007 Scientific Sessions from a retrospective analysis of healthcare claims in more than 20,000 patients with type 2 diabetes found that the initiation of insulin therapy with insulin glargine (Lantus(R)) was associated with a lower incidence rate of subsequent myocardial infarction (MI), as compared with NPH insulin.
Taxotere(R) recorded further strong growth during the quarter in Europe (up 16.8%) and in the “Other Countries” region (up 22.5%). In the United States, net sales of the product were up 8.3%, in line with the growth rate achieved in the previous quarter.
In December, sanofi-aventis filed an application with the European Medicines Evaluation Agency (EMEA) to include Taxotere(R) in combination with Herceptin(R) as an adjuvant treatment for breast cancer, on the basis of the BCIRG-006 study.
In December, results presented to the 30th annual San Antonio Breast Cancer Symposium (SABCS) showed that for women with early stage breast cancer who have had surgery, experimental treatment with a combination of Taxotere(R) and cyclophosphamide significantly improved overall survival compared to standard anthracyclin-based chemotherapy. These results were based on a median follow-up of 7 years.
Ambien CR(TM) posted net sales of $190 million in the United States during the quarter and $751 million over the full year. Net sales of Ambien(R) IR, which went off patent in the United States on April 20, 2007, totaled euro 30 million in the fourth quarter, against euro 352 million in the comparable period of 2006. Full-year net sales of Ambien(R) IR were euro 538 million.
In Japan, sales of Myslee(R) (not consolidated by sanofi-aventis) rose by 6.4% in the fourth quarter to euro 34 million. Over 2007 as a whole, the product achieved growth of 9.8% to euro 118 million.
Under the terms of the agreement between sanofi-aventis and Astellas, sanofi-aventis will consolidate net sales generated by Myslee(R) in Japan with effect from January 1, 2008.
In the United States, Eloxatin(R), the market-leading colorectal cancer treatment as adjuvant and in the metastatic phase, recorded fourth-quarter net sales growth of 12.4% to euro 236 million. In Europe, where the introduction of generics is ongoing, fourth-quarter sales were down 36.3% at euro 79 million. In the “Other Countries” region, net sales of Eloxatin(R) rose by 19.0% to euro 50 million.
Net sales of Tritace(R), adversely impacted by generic competition in Canada, fell by 28.3% in the fourth quarter to euro 195 million.
Acomplia(R) posted net sales of euro 21 million in the fourth quarter and euro 79 million over the full year.
In November, the European Commission endorsed the positive opinion of the European Medicines Evaluation Agency (EMEA) for Acomplia(R), to include type 2 diabetes trial results into the European label (section 5.1). This decision was based on the results of the SERENADE study, the first clinical trial to assess Acomplia(R) in glycemic control for type 2 diabetic patients not already taking medication for their condition.
Xyzal(R), a new prescription oral antihistamine, was launched by sanofi- aventis and UCB in the United States at the start of October 2007. Fourth- quarter net sales were euro 8 million. At end December, Xyzal(R) accounted for 5.2% of new prescriptions (NRX IMS NPA weekly).
On June 19, 2007, the U.S. District Court for the Southern District of New York upheld the validity and enforceability of the U.S. patent covering clopidogrel bisulfate, the active ingredient of Plavix(R), and issued a permanent injunction enjoining Apotex from marketing its generic clopidogrel bisulfate in the United States prior to the expiration of the patent. Apotex had launched a generic clopidogrel bisulfate in August 2006, following which the U.S. District Court for the Southern District of New York awarded sanofi- aventis a temporary injunction on August 31, 2006 ordering Apotex to halt further sales of its generic clopidogrel bisulfate, without however ordering a recall of products already shipped. The main patent protection for this product has now been maintained in the United States until November 2011.
In the United States, sales of Plavix(R) (consolidated by BMS) reached $1,180 million in the fourth quarter, compared with $348 million in the fourth quarter of 2006 when the product was affected by the availability of a generic version. Full-year sales of Plavix(R) totaled $4,072 million, compared with $2,672 in 2006.
In Europe, fourth-quarter net sales of Plavix(R) were 5.0% higher at euro 458 million, though sales are still affected by parallel imports in Germany.
In the “Other Countries” region, sales growth is accelerating, reaching 27.8% in the fourth quarter (to euro 225 million), driven by the product’s success in Japan where the pace of sales growth was boosted in May by the decision of the authorities to lift the two-week limit on prescriptions. Fourth quarter sales in Japan were euro 27 million, against euro 4 million in the comparable period of 2006. Over the full year, Plavix(R) recorded Japanese sales of euro 61 million, compared with euro 11 million in 2006.
(1) See Appendix 1 for a definition of financial indicators, and Appendix 6 for a description of selected items
Worldwide presence(1) of Aprovel(R)/ Avapro(R)/ Karvea(R)
Fourth-quarter worldwide sales of Aprovel(R)/Avapro(R)/Karvea(R) were euro 480 million, an increase of 7.6%.
In November, the United States Food and Drug Administration (FDA), based on efficacy data from two clinical trials involving over 1,200 patients with moderate or severe high blood pressure, approved Avalide(R) (irbesartan, hydrochlorothiazide) as the first combination therapy for initial use in patients likely to need multiple drugs to achieve blood pressure goals.
Net sales by division - Human Vaccines
Fourth-quarter consolidated net sales for the Human Vaccines business were down 15.3% at euro 649 million. This decrease reflects earlier shipments of influenza vaccines than in 2006, when a substantial proportion of shipments were delayed to the fourth quarter. As a result, net sales of influenza vaccines were down 40.4% at euro 245 million. Excluding influenza vaccines, net sales for the Human Vaccines business rose by 13.8% in the quarter.
Adacel(TM) (adult and adolescent tetanus-diphtheria-pertussis booster) and Menactra(R) performed very strongly in the fourth quarter, with net sales up 44.0% to euro 38 million and up 73.5% to euro 71 million respectively due to improved supply. An extension to the license for Menactra(R), covering children aged 2 to 10, was obtained in the United States in October 2007.
Over the full year, consolidated net sales for the Human Vaccines business rose by 14.5% to euro 2,778 million. Net sales of Menactra(R) advanced by 86.1% to euro 415 million, and net sales of Adacel(TM) increased by 64.5% to euro 234 million. Sanofi pasteur produced over 180 million doses of seasonal influenza vaccines in 2007, reinforcing its position as world leader: the number of doses shipped represented an estimated 40% of the world market(5). Excluding sales of H5N1 vaccines, sales of seasonal influenza vaccines rose by 2.6%.
Fourth-quarter sales at Sanofi Pasteur MSD, the joint venture with Merck & Co in Europe, rose by 44.4% on a reported basis to euro 371 million, buoyed by the success of Gardasil(R) (net sales of euro 160 million).
Sanofi Pasteur MSD began marketing Gardasil(R) in Europe at the end of 2006. This product, the first vaccine against papillomavirus infections (which cause cervical cancer), is now sold in all 19 European countries covered by the joint venture.
Sanofi Pasteur MSD achieved 2007 full-year sales of euro 1,040 million, up 43.6% on a reported basis. Net sales of Gardasil(R) for the year totaled euro 341 million. Sanofi Pasteur MSD sales are not consolidated by sanofi-aventis.
Net sales fell slightly in Europe in the fourth quarter, mainly as a result of the continuing decline in net sales in Germany. Over 2007 as a whole, net sales were down by 0.4%, with the introduction of generics of Eloxatin(R) paring approximately 1.6% off growth for the period.
In the United States, fourth-quarter net sales were down 8.5%, affected by generics of Ambien(R) IR (which went off patent on April 20) and lower influenza vaccine sales (a substantial proportion of shipments having been postponed to the fourth quarter in 2006, making for a tough comparative). Excluding the effect of generics of Ambien(R) IR and of timing differences in shipments of vaccines, net sales growth in the United States would have been 14.4%. Over 2007 as a whole, net sales rose by 3.8%. After excluding the effect of generics of Ambien(R) IR from April 2007, net sales in the United States rose by 15.1%.
Fourth-quarter net sales in “Other Countries” increased by 3.8%, below the full-year growth rate. Excluding the effect of the repurchase of inventories from Astellas and Chugai following the signature of agreements with these two companies on the buyout of several products and the effect of timing differences in shipments of vaccines, fourth-quarter sales growth in this region would have been 7.0%.
Adjusted consolidated income statement
The adjusted consolidated income statement is presented in Appendix 3.
Refer to Appendix 1 for a definition of “adjusted net income”, and to appendix 4 for a reconciliation of the consolidated income statement to the adjusted consolidated income statement.
Fourth quarter of 2007
The fourth quarter saw a marked fall in the dollar against the euro of 12.4%, compared with an average fall of 8% over the first nine months of the year.
Sanofi-aventis net sales for the fourth quarter of 2007 fell by 6.0% on a reported basis to euro 6,911 million.
Gross profit was euro 5,257 million. The gross margin ratio was 76.1%, against 76.5% for the fourth quarter of 2006. Royalty income rose by 36.0%, mainly due to a sharp rise in sales of Plavix(R) in the United States versus the fourth quarter of 2006 (when the product faced competition from a generic version), and despite the discontinuation of royalties on fipronil. The ratio of cost of sales to net sales was 28.4% (compared with 26.6% in the fourth quarter 2006), largely as a result of the introduction of generics of Ambien(R) IR in the United States and timing differences in sales of influenza vaccines between 2006 and 2007.
Research and development expenses rose by 5.0%. This includes the effect of discontinuing development of the ciclesonide/formoterol combination, the rights for which were returned to Nycomed.
Selling and general expenses totaled euro 1,996 million, representing a marked reduction of 7.3% relative to the fourth quarter of 2006. The ratio of selling and general expenses to net sales was 28.9%, against 29.3% in 2006.
Operating income - current(1) fell by 13.7%, and represented 28.4% of net sales versus 30.9% in 2006. This fall was due entirely to the euro/dollar exchange rate and to timing differences in sales of influenza vaccines.
A restructuring charge of euro 87 million (euro 60 million after tax) was recognized to cover a new program of cost adaptation measures in Germany.
Net financial expenses came to euro 28 million, against net financial income of euro 66 million in the comparable period of 2006 (the fourth quarter of 2006 included a gain of euro 101 million on the sale of the interest in Rhodia). Interest expense on debt was euro 47 million, compared with euro 36 million for the fourth quarter of 2006, with the positive effect of debt reduction more than canceled out by the impact of higher interest rates.
Income tax expense was euro 464 million, compared with euro 534 million in the fourth quarter of 2006. The reported tax rate was 25.1%, against 27.2% for the comparable period of 2006. The settlement of various tax disputes resulted in the release of euro 93 million of provisions (treated as a selected item).
The share of profits from associates was euro 178 million, versus euro 50 million for the fourth quarter of 2006, thanks to the sharp rise in sales of Plavix(R) in the United States. The share of after-tax profits from territories managed by BMS (primarily the United States) under the Plavix(R) and Avapro(R) alliance was euro 149 million, versus euro 12 million in the fourth quarter of 2006.
Minority interests totaled euro 97 million, compared with euro 103 million in the fourth quarter of 2006. This line includes the share of pre-tax profits paid to BMS from territories managed by sanofi-aventis (euro 96 million, compared with euro 98 million in the fourth quarter of 2006).
Adjusted net income was up 6.2% at euro 1,462 million, and adjusted earnings per share (adjusted EPS) was euro 1.09 (6.9% up on the 2006 fourth- quarter figure of euro 1.02), based on an average number of shares outstanding of 1,335.3 million in the fourth quarter of 2007 and 1,348.8 million in the fourth quarter of 2006.
Excluding selected items (see Appendix 5), adjusted net income was euro 1,429 million, 4.5% up on the fourth quarter of 2006 (euro 1,368 million), and adjusted EPS was euro 1.07, 5.9% up on the fourth quarter of 2006 (euro 1.01).
Expressed in U.S. dollars(2) and excluding selected items, adjusted net income was $2,071 million (up 17.3% on the 2006 fourth-quarter figure) and adjusted EPS was $1.55 (up 18.3% on the 2006 fourth-quarter figure).
(2) U.S. dollar figures obtained by translating euro-denominated figures at the average exchange rate for the period: 1.449 for Q4 2007 (1.290 for Q4 2006) and 1.371 for FY 2007 (1.256 for FY 2006)
2007 full year
Sanofi-aventis generated 2007 full-year net sales of euro 28,052 million, down 1.1% on a reported basis.
Gross profit was down 1.4% at euro 21,636 million. The gross margin ratio was 77.1%, versus 77.3% in 2006. The availability of generics of Ambien(R) IR from April 2007 adversely affected the ratio of cost of sales to net sales, which rose from 26.6% to 27.0%. The weakening dollar and the discontinuation of royalties on fipronil restricted growth in other revenues to 3.5% (to euro 1,155 million), despite strong growth for Plavix(R) in the United States.
Research and development expenses rose by 2.4% (5.5% excluding the effect of exchange rates).
The cost adaptation measures initiated in 2006 and 2007, combined with tight cost control, helped to reduce the ratio of selling and general expenses to net sales by additional 1.4 points compared with 2006, to 26.9%. Overall, selling and general expenses fell by 5.8% year on year, to euro 7,554 million. Excluding the effect of exchange rates, selling and general expenses decreased by 2.1%.
Other current operating income (net of expenses) totaled euro 215 million, against euro 275 million in 2006. In 2007, this line includes an expense of euro 61 million (euro 42 million after tax, treated as a selected item) on the harmonization of welfare and healthcare plans for the Group’s retirees.
Operating income - current(1) was virtually unchanged at euro 9,617 million. The operating margin ratio improved by 0.4 of a point to 34.3%. Excluding the effect of exchange rates, operating income - current advanced by 6.5%.
The financial statements include a restructuring charge of euro 137 million (euro 95 million after tax) for the ongoing cost adaptation program launched in France in 2006 and for a new program initiated in Germany.
Net financial expense was euro 139 million, compared with euro 80 million in 2006. Interest expense on debt amounted to euro 223 million, compared with euro 286 million in 2006.
Income tax expense totaled euro 2,572 million, versus euro 2,816 million in 2006. The 2007 figure includes a net gain of euro 337 million relating to movements in provisions for tax risks and settlements of tax disputes, and a deferred tax expense of euro 51 million related to cuts in tax rates in Germany, Spain and the United Kingdom. The 2006 figure was influenced by the low income tax charge arising on the Exubera(R) gain. The effective tax rate for 2007 was 30.6%, unchanged from the 2006 figure.
The share of profits of associates was euro 760 million, against euro 559 million for 2006. The share of after-tax profits from territories managed by BMS under the Plavix(R) and Avapro(R) alliance was euro 525 million, versus euro 320 million in 2006. There was an increase in the contribution from Merial.
Minority interests came to euro 419 million, compared with euro 393 million in 2006. This line includes the share of pre-tax profits paid to BMS from territories managed by sanofi-aventis (euro 403 million, versus euro 375 million in 2006).
Adjusted net income rose by 1.0% to euro 7,110 million, while adjusted earnings per share (adjusted EPS) was euro 5.28 (1.0% higher than the 2006 figure of euro 5.23), based on an average number of shares outstanding of 1,346.9 million in 2007 and 1,346.8 million in 2006.
Excluding selected items (see Appendix 5), adjusted net income was euro 6,961 million (up 5.9% on the 2006 figure of euro 6,571 million), and adjusted EPS was euro 5.17 (up 5.9% on the 2006 figure of euro 4.88).
Expressed in U.S. dollars(2) and excluding selected items, adjusted net income was $9,544 million (up 15.6% on the 2006 figure) and adjusted EPS was $7.09 (up 15.7% on the 2006 figure).
(2) U.S. dollar figures obtained by translating euro-denominated figures at the average exchange rate for the period: 1.449 for Q4 2007 (1.290 for Q4 2006) and 1.371 for FY 2007 (1.256 for FY 2006)
2007 consolidated statement of cash flow and balance sheet at December 31, 2007
Operating cash flow before changes in working capital was euro 7,917 million, compared with euro 7,610 million in 2006.
Working capital needs increased by euro 811 million, compared with euro 1,006 million in 2006.
Investing activities generated a net cash outflow of euro 1,716 million over the period.
Acquisitions of property, plant and equipment and intangibles amounted to euro 1,610 million, essentially comprising investment in industrial plant and equipment and contractual payments for intangible rights. These acquisitions of intangible rights (euro 231 million in 2007) mainly comprise the buyout of commercial rights over products (including Panaldine(R) in Japan) and payments made under collaboration and marketing agreements with partners including Regeneron, Oxford BioMedica (TroVax(R)), UCB (Xyzal(R)), Crucell N.V. and Acambis.
Acquisitions of investments (euro 435 million) mainly comprised euro 186 million on the buyout of preferred shares issued by Carderm Capital LP (a subsidiary of sanofi-aventis) and euro 218 million on the purchase of 12 million shares in Regeneron, taking the interest held by sanofi-aventis to approximately 19% of the capital.
After-tax proceeds from disposals (euro 329 million) included receipt of the contingent CSL purchase consideration of $250 million.
After a dividend payout of euro 2,373 million and the acquisition of 29.4 million treasury shares for euro 1,806 million, net cash generated during 2007 was euro 1,561 million, enabling sanofi-aventis to reduce net debt from euro 5.8 billion at December 31, 2006 to euro 4.2 billion at December 31, 2007. Gearing stood at 9.5% at December 31, 2007, compared with 12.6% at December 31, 2006.
2008 Guidance(5)
Barring major adverse events, sanofi-aventis expects 2008 full-year adjusted EPS excluding selected items(1) to grow around 7%, calculated at constant euro/dollar parity (1,371). Sensitivity to the euro/dollar exchange rate is estimated at 0.5% of growth for a 1-cent movement in the exchange rate.
Dividend
At its February 11, 2008 meeting, sanofi-aventis Board of Directors established the agenda and the draft resolutions to be submitted to the Shareholders’ Ordinary Annual General Meeting of May 14, 2008. It notably decided to propose to the General Meeting to approve a dividend of euro 2.07 per share. This would represent an increase of 18.3% on the previous year (euro 1.75). The dividend payment date will be May 21, 2008.
(1) Refer to Appendix 1 for a definition of financial indicators, and to Appendix 6 for details of selected items.
Our R&D teams have made progress on the key objectives announced at the R&D Day in September 2007.
During 2007, 21 compounds moved into the development phase of which 16 in pharma. In 2007, sanofi-aventis filed submissions for the first-ever intradermic influenza vaccine and for Aquilda(R) (Satavaptan), a treatment for hyponatremia. The ongoing efforts to broaden access to Menactra(R) led to the granting of FDA approval in 2007 for the 2-10 age bracket.
A major collaboration agreement was signed with Regeneron, covering the discovery and development of human monoclonal antibodies, with the objective of bringing at least two compounds into development every year. Under this agreement, an antibody against the Interleukin-6 receptor (IL-6R) has already started clinical trials in rheumatoid arthritis. It is due to be followed by an antibody against Delta-like ligand-4 (Dll4), scheduled to start clinical development in 2008 in oncology.
A number of other collaboration agreements have been signed in the field of vaccines, including those with Acambis (to develop vaccines against Japanese encephalitis and West Nile virus), with SSI (to develop a new tuberculosis vaccine) and with Crucell (in monoclonal rabies antibodies), plus an alliance with the Institut Pasteur in malaria.
Progress to date on our ongoing clinical development suggests that we remain on track for our forecast of around 30 potential filings by end 2010.
The main developments in our R&D portfolio are described below:
Metabolic disorders
Results from phase IIb trials on AVE5530, a cholesterol absorption inhibitor, showed a significant reduction in LDL at different doses, confirming the potential benefits of this product. Its non-systemic mode of action opens up the possibility of avoiding drug interaction. AVE5530 has the potential to be used as monotherapy or in combination with statins. A phase III program comprising a number of trials, including an evaluation over a 12- month treatment period, will start in the second half of 2008. Filing for approval is scheduled for the second half of 2010, both as monotherapy and in fixed combination with a statin.
After consultation with the healthcare authorities, the phase III program for the GLP-1 agonist AVE0010 will begin in the first quarter of 2008. The program will include over 3,000 diabetic patients and will evaluate a once-a- day injection of AVE0010 in combination with the principal existing treatments (metformin, sulfonylurea insulin), as well as a comparison with exenatide and a monotherapy study. Filing for approval is expected in 2010. A prolonged release formulation is currently being evaluated in phase I.
Results from phase IIb trials of AVE2268, a new renal SGLT2 inhibitor, are due in the first half of 2008, with phase III scheduled to start in the second half of 2008. This product has a novel action, and is expected to improve glycemic control at all stages of diabetes.
The program to develop rimonabant in diabetes already includes 3,400 out of the planned total of 5,700 patients. Results of the ARPEGGIO study, evaluating rimonabant in combination with insulin, will be presented to the American Diabetes Association in June 2008. Filing for approval in type II diabetes is expected in 2009, followed by filing for a fixed rimonabant/metformin combination in 2010.
Results from the STRADIVARIUS study, evaluating rimonabant in atherosclerosis, will be presented to the American College of Cardiology in March 2008, and the results of the ADAGIO trial, evaluating rimonabant in patients with dyslipidemia, will be presented to the European Atherosclerosis Society in April 2008..
Enrolment of patients to the CRESCENDO morbidity/mortality study is ongoing. Over 14,000 out of the planned 17,000 have been enrolled to date.
Thrombosis
After consultation with the healthcare authorities, the large-scale phase III program for the ultra low molecular weight heparin AVE5026, involving over 10,000 patients, is being put into place. Positive results from phase IIb point to AVE5026 as a potential successor to Lovenox. AVE5026 is a powerful anti-coagulant with pharmaco-dynamic properties that go beyond anti-Xa factor activity. It is not associated with food interaction due to the subcutaneous mode of administration, giving total bioavailability. AVE5026 has the potential to offer better tolerance (reduced bleeding, no drug interaction, antiXa/IIa ratio of over 30). Filing for approval is scheduled for 2010 in the prevention of venous thromboembolic events in patients requiring hip or knee replacement, receiving chemotherapy or undergoing abdominal surgery.
Filing for approval in the prevention of venous thromboembolic events in medical patients is scheduled for 2011.
Idrabiotaparinux (biotinylated idraparinux) is a long-acting selective neutralizable factor Xa coagulation inhibitor, administered by weekly subcutaneous injection. Enrolment of patients to the EQUINOX bioequipotency study in deep vein thrombosis is now complete, and one-third of the patient population for the CASSIOPEA study in pulmonary embolism has been recruited to date. Filing for approval in the treatment of deep vein thrombosis and pulmonary embolism is scheduled for 2009.
Enrolment to the BOREALIS-AF comparative study, designed to assess the efficacy of biotinylated idraparinux versus anti vitamin K in the prevention of stroke and systemic embolism in patients with atrial fibrillation, has now begun. Filing for approval in this indication is scheduled for 2011.
Given the results from AVE5026, and as part of the portfolio rationalization process, sanofi-aventis has decided to discontinue the development of hexadecasaccharide.
Cardiovascular
Results from the ATHENA study, assessing the potential morbidity/mortality benefits of Multaq(R) /Dronedarone, will be presented to the American Heart Rate Society at San Francisco in May 2008. A submission for approval by the healthcare authorities could be filed in mid-2008.
Phase IIb is ongoing for ilepatril, a novel anti-hypertensive for uncontrolled hypertension that inhibits ACE/NEP receptors. The final results will be presented to the American Heart Association at New Orleans in November 2008. The preliminary results are being used as the basis for ongoing discussions with the healthcare authorities on the phase III program.
The TAMARIS phase III program, a 1-year evaluation of the effectiveness of NV1FGF (a highly innovative gene therapy) in reducing the number of amputations in patients with critical lower limb ischemia, is under way. Filing for approval in this indication is scheduled for 2010.
Central Nervous System
Results from the EPLILONG phase III study demonstrate that eplivanserin, a 5-HT2A antagonist, significantly reduces WASO (Wake After Sleep Onset) and the number of nocturnal wakings reported by the patient at 6 to 12 weeks, compared with placebo.
This beneficial effect on sleep has also been confirmed by polysomnography in the results from the EPOCH phase III study, which showed that eplivanserin reduces WASO at 3 weeks (significant difference) and 6 weeks and noctu
