Posted by Phillipa on August 14, 2008, at 12:24:51
In reply to Re: Bifeprunox not approved » Jeroen, posted by Marty on August 14, 2008, at 12:12:32
Don't know anymore but the latest addition to google. Phillipa
Phase III Europe; rejected by FDA in USFull specifications
--------------------------------------------------------------------------------Bifeprunox mesilate is a novel atypical antipsychotic agent under development by Solvay Pharmaceuticals as a treatment for schizophrenia and potentially conditions such as bipolar disorder.
Solvay and Lundbeck, its European marketing partner, had hoped to file for regulatory approval in Europe in 2006, with launch to follow in 2007. However, they now plan additional clinical work to strengthen the registration dossier and filing is not now expected before 2008.
In the US, meanwhile, Solvay and marketing partner Wyeth filed for regulatory approval with the FDA in October 2006. In August 2007, the companies received the disappointing news that their NDA for bifeprunox as a treatment for schizophrenia had been rejected.
The FDA expressed concerns about both the efficacy and safety of bifeprunox. Subsequently, Wyeth decided to pull out of the agreement and all North American rights to bifeprunox have now been returned to Solvay.
DOPAMINE PARTIAL AGONISTS REPRESENT A NEW CLASS OF ATYPICALS
The first generation of atypical antipsychotic drugs, which entered clinical practice over a decade ago, share the common property of dopamine D2 receptor antagonism.This mode of action is believed to be the primary pharmacological mechanism by which antipsychotic drugs ameliorate the positive, psychotic symptoms of schizophrenia.
Bifeprunox differs from first-generation atypical antipsychotics in that it acts as a partial D2 agonist. This property is shared by aripiprazole, a drug already marketed in Europe and the US for treatment of schizophrenia.
"All North American rights to bifeprunox have now been returned to Solvay."In contrast to D2 receptor antagonism, partial D2 agonism is believed to decrease dopamine activity in an overactive dopamine system while simultaneously increasing dopamine activity in regions of the brain where dopaminergic activity is too low.
By blocking overstimulated receptors and stimulating underactive ones, partial D2 agonists act as dopamine stabilisers.
In common with aripiprazole, bifeprunox also acts as a serotonin, 5-HT1A agonist. This property may contribute to efficacy against the negative symptoms of schizophrenia and reduce the likelihood of extrapyramidal symptoms (EPS).
This new class of atypical antipsychotic drugs, sometimes described as next-generation antipsychotics, is seen as an attractive treatment option for schizophrenia and potentially the acute manic phase of bipolar disorder.
INCREASING TREATMENT OPTIONS
Despite an expanding range of antipsychotic drugs, which have greatly improved treatment prospects for patients with schizophrenia, there remain significant treatment gaps. New antipsychotic drugs are needed with broader efficacy to treat patients unresponsive to current agents.Although the atypical antipsychotics offer improved safety and tolerability over conventional typical antipsychotics, especially with respect to EPS, drug safety is still an issue. Significant weight gain leading to metabolic disturbances (diabetes, heart disease), sexual dysfunction, hyperprolactinaemia, and cardiotoxicity are unwelcome side effects associated with some currently used atypical drugs.
Poor tolerability leads to poor treatment compliance and risk of relapse. Thus, there is a need for antipsychotics with improved safety and tolerability to improve compliance and outcome.
A placebo-controlled, dose-finding phase II trial in patients with schizophrenia showed that bifeprunox was both efficacious and well tolerated. Importantly, treatment with bifeprunox did not appear to cause some of the side effects seen with other atypicals agents in routine use, such as weight gain, hyperprolactinaemia and cardiotoxicity. Thus, in addition to a low incidence of EPS, similar to placebo, other benefits that may arise from clinical use of bifeprunox include:
No weight gain
No increase in prolactin levels
No adverse effect on blood lipids
No adverse effects on blood glucose levels
No QTc prolongation
If these promising findings are confirmed in the larger phase III trials now underway then bifeprunox is likely to be well received by the market."Bifeprunox differs from first-generation atypical antipsychotics in that it acts as a partial D2 agonist."WYETH ENDS PARTNERSHIP WITH SOLVAY
While Lundbeck secured worldwide development and marketing rights to bifeprunox outside Canada, Japan, Mexico and the US, Solvay had forged a partnership with Wyeth for the key US market. The co-development and marketing agreement between the two companies, which was signed in April 2004, focused on four of Solvay's investigational antipsychotic drugs: bifeprunox, SLV-310, SLV 313 and SLV-314.
Wyeth's decision to end the partnership with Solvay for bifeprunox and the other compounds arose from the FDA decision to reject bifeprunox and the belief that there was insufficient commercial value in the product for the two companies to share. All development and commercialisation rights in North America for bifeprunox, as well as global rights for the other compounds, have been returned to Solvay.
MARKETING COMMENTARY
Affecting around 1% of the general population, schizophrenia is a severe and debilitating mental illness. Antipsychotic drugs are the cornerstone of the management of schizophrenia and are designed to address the core symptoms of the illness, which include positive, negative, cognitive and affective symptoms.
Bifeprunox is one four antipsychotic drugs currently in advanced-stage development for treatment of schizophrenia. Analysts had believed that of the four, bifeprunox was the most likely to succeed, given its promising efficacy and side-effect profile.
However, this is now in doubt given its failure to secure FDA approval, which stemmed largely from the drug's inability to perform as well or better than existing antipsychotic drugs. Physicians are unlikely to switch patients from a drug that is working to one that may not work as well.
In the US six atypical agents currently compete for a share of the antipsychoti
poster:Phillipa
thread:846140
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