Lundbeck Reveals Mechanism of Action of its “Mixed Serotonin Modulator and Stimulator” Antidepressant LuAA21004

Implications: Lundbeck has now disclosed the mechanism of action of its “mixed serotonin modulator and stimulator,” albeit buried in a first quarter report.   Data on LuAA21004, Lundbeck’s lead antidepressant jointly in development with Takeda, was released at the Scandinavian College of Neuro-Psychopharmacology this past April.  So far, the drug has been shrouded in some mystery with only speculation as to its novelty, especially when viewed against the large pool of generic SSRIs/SNRIs either in the market or soon entering it.  Lundbeck and Takeda hope to advance LuAA21004 through an ambitious Phase III program with an anticipated launch by 2011 just before generic Lexapro arrives.

Analysis: Lundbeck has disclosed LuAA21004 as a mixed serotonin 5-HT3 receptor antagonist and 5-HT1 partial agonist.   In prior GLG News, I have suspected serotonin 5-HT1a partial agonism for this investigational drug, which, when weighed against the latest evidence, is no longer the compelling receptor target for depression or anxiety that was once hypothesized.   Drugs primarily aimed at 5-HT1a have had a couple recent development failures on the depression/anxiety front.  5-HT3 antagonists have been used primarily as anti-emetics, especially for chemotherapy induced nausea/vomiting, with a couple targeting irritable bowel syndrome.  I have not seen much data on 5-HT3 receptor for depression.  Lundbeck and partner Takeda appear to be advancing this compound rapidly into Phase III following positive Phase II proof-of-concept data last fall.  Hopefully the Phase III data will be a bit more compelling than the receptor profile quietly announced over the last few months.