Sanofi unveils new antidepressant

Saredutant is designed to block the effects of a G protein coupled receptor (GPCR) called neurokinin 2 (NK2). The drug could prevent neurochemical changes induced by different stressful conditions in brain regions implicated in depression and anxiety disorders.

The clinical results were announced alongside the company's financial results after what Sanofi themselves described as "not an easy year" with several "major adverse events."

Established antidepressant treatments work by causing serotonin levels to be increased. However, a report in the Journal of Clinical Psychology claimed that some mutations in the gene 5HT transporter gene could predispose patients to not respond well to these treatments. Therefore, there is a need for antidepressant s based on a different mechanism of action.

Antidepressant drugs also fail because they are often associated with a variety of unpleasant side effects, such as decreased sex drive, gastrointestinal disorders and weight gain, which can lead to patients stopping taking their medication.

Sanofi expects its once-a-day drug to have low incidence of these side effects. The company is conducting several Phase III trials looking at safety, efficacy (both short and long-term) and the effects of sudden withdrawal.

Saredutant is in development to treat major depressive disorder and General Anxiety Disorder. Of four Phase III studies for depression, two showed statistically significant results and two studies were not statistically significant versus placebo. The results from four other Phase III studies are expected this year or in 2008.

In a recent Phase IIb study, 44 per cent of patients responded to treatment with saredutant with 37 per cent classed as being in remission after six weeks of treatment.

The side effects of saredutant were studied compared to GlaxoSmithKline's $1.2bn (€926m) antidepressant drug Seroxat/Paxil (paroxetine). Incidence of nausea and diarrhoea was more than halved with Sanofi's drug and the proportion of patients who felt any side effect was reduced by 10 per cent.

GPCRs are the largest known class of drug targets with proven therapeutic benefits. Drugs that interact with these proteins make up nearly 40 per cent of the top 50 selling drugs worldwide. The proteins are responsible for responding to signals outside the cell and translating this into biological processes inside the cell.

NK2 is one of three tachykinin receptors. It binds to neurokinin A and induces the production of a chemical called inositol triphosphate, which is found in elevated levels in patients suffering from depression.

There are several other drugs in development that also target the GPCR, NK2, although these drugs are not for depression therapy. One example is nepadutant from Menarini, the first Italian pharma company. Currently conducting Phase II trials, the drug is designed to treat irritable bowel syndrome.

AstraZeneca was also developing a NK2 inhibitor drug called M274773, although it no longer appears on the firm's pipeline listing.

Meanwhile, Sanofi also announced that it has dropped two experimental anticancer drugs from its pipeline. SR31747 was in Phase IIb trials for prostate cancer and tirapazamine was a Phase III drug candidate, designed to treat head and neck cancer.

SR31747 binds to two proteins: sigma 1 receptor and emopamil-binding protein (EBP) and can inhibit tumour growth by preventing cell proliferation.

Tirapazamine (SR 259075) is activated by hypoxia to make cancer cells more sensitive to chemotherapy.