AstraZeneca and Targacept begin depression trials

AstraZeneca and Targacept have begun enrolling patients in phase III trials for TC-5214, a new treatment for depression.

The new drug is being developed as an adjunct treatment for patients with major depressive disorder (MDD) who have not responded to SSRI or SNRI antidepressants.

The treatment of depression became a major market for the industry in the 1990s, with the launch of Lilly’s Prozac and other drugs in the SSRI class, and Wyeth’s Efexor (in the SNRI class) but these drugs are now off patent, and little clinical progress has been made in the field since.

TC-5214 works by blocking the nicotinic channel, based on evidence that depression is related to overstimulation of neuronal nicotinic receptors (NNRs) and other receptors in the brain that are activated by the neurotransmitter acetylcholine.

The companies say they expect to file for marketing authorisation in the US in the second half of 2012 and in 2014 in Europe.

The drug’s Renaissance development programme will include two fixed dose phase III studies and two flexible dose phase III studies to evaluate TC-5214. The programme also includes a double blind, placebo controlled long-term safety study in which patients would receive TC-5214 or placebo for up to one year.

The companies say research shows that in many cases patients fail to respond to SSRIs and SNRIs.

They cit a large-scale trial conducted by the US National Institute of Mental Health called STAR*D which found around 63% of patients did not achieve remission with first-line treatment with the SSRI antidepressant citalopram.

A phase II clinical study to assess TC-5214 as a second line ‘switch’ monotherapy treatment for MDD is targeted to start in 2010.

Andrew McConaghie