Dapoxetine: LY 210448

Dapoxetine [LY 210448], a selective serotonin reuptake inhibitor (SSRI), is structurally related to fluoxetine with antidepressant activity. Dapoxetine is the D-enantiomer of LY 243917 and is 3.5 times more potent as a serotonin reuptake inhibitor than the L-enantiomer.

Dapoxetine was in phase I clinical trials in the US with Eli Lilly as an antidepressant, but no recent development has been reported for this indication. However, development is underway for the treatment of premature ejaculation, with phase III trials for this indication being completed in the US.

The phase II trial for the treatment of premature ejaculation was conducted by PPD GenuPro, a subsidiary of PPD, which was established from a collaboration between Eli Lilly and PPD for the development of drugs to treat genitourinary disorders. Both Lilly and PPD had an option to re-license dapoxetine upon completion of phase II trials, but neither company exercised its option, and the rights remained with PPD GenuPro.

In December 2003, PPD Inc. acquired from Eli Lilly and Co. the patents for dapoxetine for development in the field of genitourinary disorders. As part of the transaction, PPD and Lilly terminated their existing license agreement for dapoxetine.

In December 2000, PPD GenuPro granted an exclusive, worldwide license for dapoxetine to ALZA Corporation, a wholly owned subsidiary of Johnson & Johnson. ALZA will be responsible for development, manufacturing and commercialisation of dapoxetine for urological indications, including premature ejaculation. It will make initial, milestone and royalty payments to PPD GenuPro, a portion of which will be paid to originator Eli Lilly.

PPD Inc. received a milestone payment relating to the ongoing development of dapoxetine for premature ejaculation in July 2003.

In December 2003, PPD and ALZA amended the dapoxetine license to allow PPD to receive a fixed-sum cash payment apon NDA approval. In return for this, ALZA will not have to make sales-based payments for a period of time following the approval of dapoxetine.

If dapoxetine is approved by the US FDA for premature ejaculation, the drug will be marketed in the US by Ortho-McNeil Pharmaceutical, Inc.

In December 2004, ALZA Corporation submitted a new drug application to the FDA for dapoxetine hydrochloride in the treatment of premature ejaculation. If approved by the FDA, dapoxetine hydrochloride will be marketed in the US by Ortho-McNeil Pharmaceutical, Inc.

Johnson & Johnson plans to support the launch of dapoxetine for premature ejaculation with a `responsible' direct-to-consumer advertising campaign.

In May 2005, Johnson & Johnson presented data from two phase III trials involving dapoxetine for the treatment of premature ejaculation, during the 100th Annual Scientific Meeting of the American Urological Association (AUA-2005). Results on drug interactions and pharmacodynamics of dapoxetine were also presented during this meeting.

Dapoxetine also appears to be a useful adjunct to morphine, lowering the threshold for analgesia, although the compound itself has negligible analgesic activity.

In December 2003, PPD, Inc. acquired from Eli Lilly and Company the patents for dapoxetine for development in the field of genitourinary disorders. Under the terms of the agreement with Lilly, PPD will pay Lilly US$65 million in cash. PPD will also pay Lilly a royalty on net sales of dapoxetine in excess of a certain threshold of annual net sales. As part of the transaction, PPD and Lilly terminated their existing license agreement for dapoxetine.