Sanofi-Aventis: pipeline update

Of the 31 new drugs Sanofi's head of research, Dr Marc Cluzel said the company plans to file to drug regulators by the end of 2010, a large proportion are New Chemical Entities (NMEs). These are defined by the US Food and Drug Administration (FDA) as drugs that contain ingredients that have never before been marketed in the US, and therefore represent the more innovative drugs in a company's pipeline. The drugs in question cross the four therapeutic boundaries that make up "the bulk" of Sanofi's R&D: cardiometabolism, central nervous system (CNS), Oncology and Vaccines. Not including vaccines, six are expected to be filed in 2008, three in 2009, and eleven in 2010. Here are some of the drugs expected to be the biggest-hitters or the first in a new class. Cardiometabolism ​ Cardiometabolism in particular is a wide ranging category that encompasses areas such as thrombosis, diabetes, hypertension and obesity. The market for these drugs is estimated to be around €100bn, according to Pierre Chancel, head of global marketing at Sanofi, and also speaking at the event. AVE5036​ is a new ultra low molecular weight heparin (LMWH) being positioned as a potential successor to the world's best selling LMWH, Lovenox, which garnered global sales of over €2.4bn in 2006. As such, this is a very important drug for Sanofi and it is currently being tested in a Phase III trial with over 10,000 patients. An initial filing for the prevention of venous thrombo-embolic events in a limited group of patients is expected in 2010, with others to follow the year after. Biotinylated idraparinux​ is a pentasaccharide that is a synthetic analogue of the functional part of heparin. It is designed to inhibit factor Xa. Originally in development as plain idraparinux, an earlier clinical trial was terminated early following a significantly higher incidence of bleeding events with idraparinux than with the comparator drug used, warfarin. This issue is now being addressed with the development of this latest formulation where the compound also has a biotin 'hook' added. This enables it to be quickly neutralised with avidin in the event of bleeding. Expected to be filed in 2009. Acomplia (​rimonabant)​ is the first CB1 inhibitor and although it has been weighted down by safety concerns as an anti-obesity drug, Sanofi still hopes to file it as a treatment for Type II diabetes in 2009. CNS ​ Saredutant​ represents a new class of anti-depressants with a better safety profile than the current drugs, especially on sexual function, claims the company. It is a NK2 receptor inhibitor. Expected to be filed next year. SSR149415​ is also a potential first-in-class drug that inhibits V1b, although it is unlikely to be filed until 2011 at least. Oncology ​ In this therapeutic category, aflibercept​ has a unique mechanism of action. It was developed in conjunction with Regeneron, which created technology to 'trap' a therapeutic target, in this case, VEGF being produced by a tumour to increase its blood vessel growth. As such, Sanofi believes it is superior to monoclonal antibodies against the same target, such as Genentech's Avastin (bevacizumab), as it should treat some indications that this drug does not. The first submission is expected next year, but as with nearly all cancer drugs, new submissions for other indications will come soon after. Vaccines ​ One of the most eagerly anticipated vaccine in the Sanofi-pipeline is Trovax​, which was recently licensed in from Oxford Biomedica. It targets the tumour antigen 5T4 and consists of a poxvirus gene transfer system, which delivers the gene for 5T4 and then stimulates the patient's body to produce an anti-5T4 immune response. The first submission is planned for 2009 The company is also targeting dengue fever​, one of the most common tropical diseases. It is a growing health concern as, on top of the 50-100 million people affected globally, cases have recently appeared in Australia and in the US. The vaccein incorporates four protein envelopes of the four dengue viral sertypes responsible for the fever and the most severe forms of the disease. All of these must be targeted for the vaccine to be effective, said Wayne Pisano, senior vice president of commercial operations and corporate strategy for Sanofi Pasteur. In the results from Phase II trials announced this week, 100 per cent seroconversion was demonstrated he added. The market is thought to in excess of €1bn and if the Phase III trials begin next year as expected, it will become the first tetravalent candidate vaccine to reach this stage.