Allergan has reported mixed top-line data from a mid-stage trial of its wrinkle treatment Botox in patients with major depressive disorder (MDD), but still thinks it is worth testing the drug in phase III.
The specialty pharma group took the decision to test Botox in depression after external research groups showed evidence of efficacy in MDD in two separate early-stage trials.
The hypothesis is that the nerves in the muscles between the eyebrows that cause frown lines – which are targeted by Botox wrinkle treatment – can stimulate parts of the brain that are overactive in depression. By using the drug to relax these muscles, the negative brain stimulation may be reduced, it is suggested.
Allergan‘s phase II study – carried out in 258 women and comparing two doses of Botox (30 and 50 units) to placebo – gave some indications of efficacy but was certainly not compelling. The lower dose was numerically better at improving depression scores than placebo, but did not reach statistical significance at the primary six-week endpoint, while the higher dose showed no benefit compared to control.
Nevertheless, Allergan’s chief R&D officer David Nicholson said the company was “encouraged by these data and the potential impact on adults with MDD”, adding that “given our in-depth and extensive clinical trial experience in … depression, we plan to move forward and develop a phase III program for a potential new treatment option for patients”.
Aside from its use as a wrinkle treatment Botox is already approved to treat various medical conditions, including chronic migraine, excessive sweating and overactive bladder among others, and is Allergan’s biggest-selling drug with turnover of $2.7bn last year.
The company’s decision to press on with the programme is clearly a gamble, but one that could have a big pay-off. Estimates vary, but some studies have suggested that up to half of all MDD patients have depression resists treatment with the usual armamentarium of antidepressant drugs, and there is an urgent need for new options.
Indeed, Botox is reportedly already being used off-label by physicians in treatment-resistant MDD – a sales stream that could be threatened if Allergan’s phase III trials are a bust. But analyst Ronny Gal of Bernstein thinks that if the gamble pays off, a market worth $2bn-$4bn could be unlocked for Botox.
“Questions still remain about the efficacy of this drug and how it will get approved but the potential market here I view as very, very significant,” said Gal.