Encouraging new Phase III data on Schering-Plough’s atypical antipsychotic Saphris have been presented at the European College of Neuropsychopharmacology meeting in Istanbul

The drug is expected to launch soon in the USA following approval in August this year for the treatment of acute schizophrenia and for acute mania or mixed symptoms in bipolar 1 disorder. Both these conditions affect millions of people worldwide.

S-P is upbeat following final results of a multinational, year-long, schizophrenia relapse prevention study (six months open-label followed by a six-months randomised double blind placebo-controlled phase involving 386 patients). These show the relapse rate was significantly lower for Saphris (asenapine)-treated patients (12% compared to 47%) for placebo).

Patients who discontinued asenapine for any reason nonetheless stayed on treatment significantly longer than patients who discontinued placebo, suggesting patients tolerate the drug – administered under the tongue – relatively well. Safety data from the study show treatment-related adverse events were higher for placebo; only 3.7% of asenapine patients had clinically significant weight gain.

Lead investigator Mary Mackle, clinical research scientist at S-P, PharmaTimes World News: “This is a very good result indeed. And because patients were stabilised and completely free of symptoms for six months before being randomised to study drug or placebo, it clearly shows asenapine prevented relapse.”

More than half of schizophrenia patients are expected to relapse within two years if untreated, rising to four out of five by five years, say experts. Antipsychotics can reduce the relapse rate so long as patients continue on treatment. Unfortunately all antipsychotic drugs to date, including the newer atypicals, have carried side effects that many patients find hard to tolerate long term, particularly weight gain.

Safety data were also presented in Istanbul this week from a year-long extension phase of a six-week study in which asenapine was compared against haloperidol, the gold standard antipsychotic. John Panagides, a research scientist at S-P, said the trial showed asenapine was associated with only modest side effects regarding weight gain, metabolic syndrome, sedation and involuntary movements: “we figure it has a very good risk benefit profile”.

Data from S-P studies suggest that compared to other typical and atypical antipsychotics, asenapine may offer both efficacy and tolerability advantages. “It may be the most potent of all the drugs in the market place right now” commented Dr Panagides. “It has a rich pharmacology and targets many many receptors, including serotonergic, alpha adrenergic, dopaminergic and histamine receptors , which may add to its effectiveness.”

A press release issued by the company in July this year reported a study on the difficult-to-treat negative symptoms of schizophrenia - apathy, lack of emotion and poor social functioning, among others. In the study, asenapine was significantly more effective than olanzapine in the reduction of negative symptoms as assessed using the 16-item Negative Symptom Assessment scale (NSA-16). ”Full results of the trial, including efficacy, safety and tolerability data, will be submitted for presentation at a medical meeting at a later date,” says the company.

A poster at ECNP led by University of California and Yale University scientists using a primate model suggests asenapine may have potential to treat cognitive impairment in schizophrenia. The researchers concluded asenapine’s effects on serotonergic receptors might also improve cognitive impairment in schizophrenia although they stress large-scale clinical studies would be needed for confirmation of these effects in patients.

In its other indication, bipolar 1 mania, or mixed symptoms, a poster at ECNP showed asenapine rapidly reduced symptoms within two days and improved scores on all 11 items of the standard measure for mania assessment – the Young Mania rating Scale within two weeks.

Asenapine was inherited from Organon which Schering-Plough acquired two years ago and is one of five products the company highlighted as its rising stars in late stage development at its R&D update last November. Although there are currently a number of competitor atypical antipsychotics available, there is considered to be an unmet need for the holy grail of therapy -an effective drug that lacks serious side effects to a sufficient degree that patients needing long-term therapy will actually continue to take it.
By Olwen Glynn Owen in Istanbul