You know Marty Keller, he put his name to the infamous Study 329 that looked at Seroxat (Paxil) and its safety and efficacy in adolescents.
After Study 329, you might be forgiven for not taking Marty and any of his research and conclusions at face value.
However, Glaxo have a drug that needs some good trial results in order to get FDA approval – you may remember I wrote about the drug, Gepirone ER, a while ago. It has been around for some years and in fact it “was determined by the FDA in June 2004 as not approvable”
I really don’t know what the FDA was fussing about as Marty Keller’s results sing the praises of Gepirone ER:
Relapse prevention with gepirone ER in outpatients with major depression
by Keller MB, Ruwe FJ, Janssens CJ, Sitsen JM, Jokinen R, Janczewski J. Department of Psychiatry and Human Behavior, Brown University, Providence, RI 02906, USA.
To evaluate long-term efficacy and tolerability of the serotonin 5-HT1A receptor agonist, gepirone extended release (ER), a multicenter, randomized, placebo-controlled relapse prevention study was performed in patients with recurrent major depression (DSM-IV criteria). Patients 18 to 70 years, with a primary diagnosis of recurrent major depression (DSM-IV; 296.3) and a screening and baseline HAMD-17 total score >/=20 were eligible. After a 3- to 14-day (dependent on pretrial medication) single-blind placebo washout period, eligible patients entered an 8- or 12-week (depending on time to remission) open-label gepirone ER treatment period. They initially received a dose of 20 mg/d gepirone ER and were titrated to a dose of 40 to 80 mg/d. Patients who achieved remission (HAMD-17 total score /=16 or discontinuation for lack of efficacy. A total of 420 patients were treated in the open-label phase. Of these, 303 (72.1%) completed the open-label phase and 250 (59.5%) fulfilled the criteria for remission and were randomized into the double-blind continuation phase (gepirone ER: n = 126; placebo: n = 124). The mean (+/-SD) final titrated dose of gepirone ER was 61.9 (+/-17.0) mg/d in the double-blind continuation phase. The relapse rate in the gepirone ER group was statistically significantly lower than that in the placebo group, 23.0% versus 34.7%, respectively (P = 0.024). During the open-label phase, adverse events that occurred in more than 5% of patients were nausea (15.7%), dizziness (13.1%), headache (12.9%), insomnia (6.2%), and vertigo (6.0%). During the continuation phase, the incidence of newly or re-emerging adverse events was similar with gepirone ER (43.7%) and placebo (42.7%). Adverse events different from those occurring during the open-label phase were not apparent. All adverse events occurred in less than 5% of patients with the exception of flu syndrome and headache. In conclusion, gepirone ER at a dose range of 40 to 80 mg/d is effective for relapse prevention in patients with recurrent major depression. It is well tolerated during long-term treatment for up to approximately one year.
I’m confused. The drug has not altered since the FDA decided they couldn’t approve it, so it’s lucky for Glaxo that Marty Keller’s study came up with the right results.
On October 10, 2002, the New York times wrote:
Akzo Nobel announced today that it was forced to delay for at least another year the release of an anti-depressant drug it is testing.
The company said its pharmaceutical division, Organon, was having a hard time recruiting patients for clinical trials of the drug, gepirone ER, formerly called Ariza. Akzo had hoped to release the drug next year for the treatment of severe depression but has now put off plans to do so until at least 2004.
”It’s going slower than we anticipated,” said Ian Cressie, a company spokesman.
“Slower than we anticipated“ was an understatement! By 2004, The NARSAD research newsletter noted:
A pyridinyl piperazine (5-HT1A) receptor agonist for the treatment of depression, gepirone (Ariza) has been awaiting FDA’s approval since May 2001. In June 2004, after asking for more clarification, the FDA announced that it has found Organon’s gepirone “Not Approvable.” Organon is planning to withdraw its application for this compound as a treatment for depressive disorder.
Then on June 15 2005 we learned: Fabre-Kramer Re-Acquires Gepirone ER Rights From Organon
HOUSTON, TX–June 15, 2005 –Fabre-Kramer Pharmaceuticals, Inc., a privately-held specialty pharmaceutical company, and Organon, the human healthcare business unit of Akzo Nobel, announced today that they have reached an agreement under which Fabre-Kramer is re-acquiring all rights related to Gepirone ER, a once-daily product being developed for the treatment of depression.
Under the agreement, Organon is returning all rights and know-how related to Gepirone ER to Fabre-Kramer, including sponsorship of NDA 21-164 for Major Depressive Disorder, which was determined by the FDA in June 2004 as not approvable. Fabre-Kramer is assuming certain obligations of Organon for ongoing pediatric trials. In the event of FDA approval of Gepirone ER, Organon will receive a milestone payment and will also receive royalties based on future sales of Gepirone ER.
Stephen J. Kramer, M.D., CEO of Fabre-Kramer, commented, “We are excited about the opportunity to continue the development of Gepirone ER. Gepirone ER represents a novel mechanism of action as a 5HT1A partial agonist, with the potential to effectively treat depression with minimal side effects. We look forward to reporting the results of two multi-center placebo-controlled Phase III clinical trials that Fabre-Kramer recently conducted. Our team has worked hard to bring safe and effective alternatives to depressed patients for whom existing therapies are not satisfactory, and Gepirone ER, if approved by the FDA, may be one such alternative.”
By ‘continuing the development’ of Gepirone ER it looks like he meant finding another buyer for it – and so we arrive back in February 2007 find that Glaxo has bought Gepirone ER and is going to try and get it approved by the FDA:
Stephen J. Kramer, M.D., CEO of FKP, commented, “We are excited about this alliance because we are confident that GSK, through its outstanding experience in the depression market will, once approved, successfully commercialise and further develop gepirone ER to help the many depressed patients for whom existing therapies are simply not satisfactory.”
So, are we going to see all the trial results I wonder? Steven J Kramer mentioned two multi-center placebo-controlled Phase III clinical trials (the Marty Keller trial is perhaps one of them?) Also mentioned above were “…ongoing pediatric trials…”
Let’s all keep an eye on this one, shall we.