Thursday, September 2, 2010

Asenapine Approved For Bi-Polar Disorder I, In Europe. Ugh.

This drug -- with a decidedly-checkered research and development history -- is branded in the US as Saphris®, and in Europe as Sycrest® (and, more background; even more, on why Pfizer bailed on developing the drug, nearly 15 years ago). Today, it was approved by the EMEA for BiPolar I Disorder -- in all European Union jurisdictions (this is an added indication -- beyond schizophrenia):

. . . .Today’s decision was based on recommendations from the European Medicines Agency (EMA) Committee for Medicinal Products for Human Use (CHMP). The Commission Decision applies to all 27 European Member States.

"Bipolar I disorder is difficult to manage, and patients frequently discontinue therapy for a variety of reasons," said Eduard Vieta, M.D., Ph.D., professor of psychiatry at the University of Barcelona, and director of the Bipolar Disorders Program of the Hospital Clinic, Barcelona, Spain. "Having multiple treatment options is vital for patients, and asenapine represents a new option for this serious disease. . . ."
* * *


Neuroleptic Malignant Syndrome

Neuroleptic Malignant Syndrome (NMS), characterised by hyperthermia, muscle rigidity, autonomic instability, altered consciousness and elevated serum creatine phosphokinase levels, has been reported to occur with antipsychotics, including asenapine. Additional clinical signs may include myoglobinuria (rhabdomyolysis) and acute renal failure. If a patient develops signs and symptoms indicative of NMS Sycrest must be discontinued.


In clinical trials, cases of seizure were occasionally reported during treatment with asenapine. Therefore, Sycrest should be used with caution in patients who have a history of seizure disorder or have conditions associated with seizures.


The possibility of a suicide attempt is inherent in psychotic illnesses and bipolar disorder and close supervision of high-risk patients should accompany treatment. . . .

Tardive dyskinesia

Medicinal products with dopamine receptor antagonistic properties have been associated with the induction of tardive dyskinesia characterised by rhythmical, involuntary movements, predominantly of the tongue and/or face. In clinical trials, cases of tardive dyskinesia were occasionally reported during treatment with asenapine. The onset of extrapyramidal symptoms is a risk factor for tardive dyskinesia. If signs and symptoms of tardive dyskinesia appear in a patient on Sycrest, discontinuation of treatment should be considered. . . .

Look for the lawsuits in about three years, from prescribing Sycrest to people who aren't profoundly ill enough -- to warrant the risk of these more-than occasionally ferocious side effects. Paging Salmon, stat.

A silver-lining? Due largely to the above side-effect profile, it remains an anemic seller, worldwide (despite Mr. Hassan's predictions of mega-blockbuster status, just two years ago).


Anonymous said...

This approval was to be expected and it was only a matter of time.

As for the AE profile you list these are mostly class effects and so are standard for any antipsychotic. The real issue is what is the difference in rates between drugs for which the data would only be available if AE data reported to FDA were to be made public.

The exception is suicide. Although there is an inherent risk in with the illness the data from the FDA AC package indicates that the primary risk comes from the drug and so this statement is really likely intended as misdirection.

I personally doubt that the weak sales are due to the AE profile as it's little different from Zyprexa. Rather it's more likely due to it being a late entrant into a crowded field (Zyprexa, Seroquel, Risperdal, Invega, Geodon, Haldol, etc.) with drugs that are likely to go off patent soon.

I didn't have an opportunity to comment on the Mother Jones article you asked me to comment on, however he basically has it right. One thing he mentions is using all cause discontinuation rates and not breaking it out into specifics. This is an important point. There are statistical implications for this as well as implications of the lack of a placebo control the effect on the determination of adverse event profiles in addition to the efficacy implications the author mentions. Lastly of course is that it appears that a flexible which may level out all cause d/c rates (which were an inappropriate surrogate for efficacy as they could be due to AEs) yet would result in clearly different efficacy rates due to suboptimal doses with the competitor's products.

I will probably not comment too much in the future but will wait to see the court cases that ensue.


Anonymous said...

Having tried Seroquel for a few days (discontinued due to anaphylaxis), I have shot down all of my shrink's suggestions WRT atypical antipsychotics and the like (Geodon, Abilify, Zyprexa, other -pines) and suggested sticking to stuff that's gone generic recently. At least there's some history, and usually nothing close to the horrible side effect profile asenapine has...