The US Food and Drug Administration (FDA) issued a 'not approvable' letter for the gepirone extended release drug, which had been submitted for the treatment of adults with major depressive disorder. The drug, a 5HT1A agonist, had shown promising trial results which were believed to be due to an agonist effect on post-synaptic serotonin inhibitors. The drug also boasted minimal side effects due to its mechanism of action (unlike alternative antidepressant treatments), and would have been the first antidepressant in the direct serotonin agonist class had it gained approval. This is the latest regulatory hurdle the drug has come up against, following a series of setbacks since the initial new drug application (NDA) back in 2001. Originally submitted by FKP's former development partner Organon, the company had anticipated launching the product in 2002, bringing a new player to the multi-billion dollar antidepressant market. However, FDA opinion back in 2002 was that further information was needed regarding the gepirone product (then provisionally named Ariza) before it could be granted marketing authorisation. Organon pushed back its estimated launch date to 2004. June 2004 saw the amended NDA handed its first 'not approvable' letter from the FDA, and a year later FKP had re-acquired the rights to the extended release gepirone product. In the event of FDA approval of the product, Organon will receive a milestone payment and royalties on future sales. Skip forward to February this year and UK pharma giant GSK has taken an interest in the drug and entered an exclusive worldwide agreement with FKP to develop, manufacture and commercialise gepirone ER and follow-on products. FKP received an undisclosed, upfront cash payment, due to be followed by milestone payments based on NDA approval and product launch. It seems the US based firm will have to wait a little longer for those instalments than it might have liked. With GSK only a few weeks ago announcing restructuring efforts and job cuts to help buffer the impact of generic competition and product safety scares, the firm also reiterated it plans to 'super invest' in certain parts of R&D and drum the most out of its late stage pipeline. The FKP deal would have fitted in nicely with this scheme, bringing a late-stage, potentially very lucrative antidepressant on board to plump the company's coffers. Three months after the GSK deal had been signed, the companies responded the 2004 FDA request for additional positive short-term studies, submitting the results in May 2007. Last Friday's decision was the result of the FDA review of those results along with newly submitted data and the previously submitted information. The disappointing news means the two companies will have to go back to the drug one more time to see if the FDA's comments can be addressed and preserve gepirone ER as a viable drug candidate. "We are evaluating the FDA's comments and working with Fabre-Kramer on our next steps," a GSK spokesperson told in-PharmaTechnologist.com.