After being approved by the FDA in 1997, Seroquel
joined the ranks of the Atypical Antipsychotics used to treat Schizophrenia. After a time, the NIMH funded a large study to compare the Atypicals that included one of the first generation neuroleptics, Trilafon
[perphenazine] – the CATIE
study. That study’s primary outcome measure was simple:
We hypothesized that there would be significant differences in the overall effectiveness of olanzapine, perphenazine, quetiapine, risperidone, and ziprasidone in treating schizophrenia that reflected variations in efficacy and tolerability. The primary outcome measure was the discontinuation of treatment for any cause, a discrete outcome selected because stopping or changing medication is a frequent occurrence and major problem in the treatment of schizophrenia. In addition, this measure integrates patients’ and clinicians’ judgments of efficacy, safety, and tolerability into a global measure of effectiveness that reflects their evaluation of therapeutic benefits in relation to undesirable effects.
Seroquel [Quetiapine] didn’t fare so well:
A finding not remarkably different from that of the "buried" Seroquel Trial 0015
from a decade before [still "buried" when CATIE
was published in 2005]:
In an earlier series, I mused guiltily that had I been on the F.D.A. Panel evaluating Seroquel
, I might’ve thought, "No great shakes, but let’s give ’em a shot. If it’s no good, doctors won’t prescribe it and the patients won’t take it.
" Well that didn’t happen. CATIE
showed what we would’ve known from Trial 0015
[had we seen it], the Schizophrenic patients stopped taking it over the other choices, new drugs and
old. But the sales of Seroquel
had risen and would continue to rise. While it’s tempting to look into the issue of weight gain, for the moment I’m going to stick with the sales side of the equation. It’s obvious that this drug isn’t a personal favorite, but I hope I laid out the basics fairly. The graph on the right is not explained by Seroquel
‘s stellar performance in Schizophrenia. In fact, a widely known study like CATIE
didn’t slow the sales
at all, because by 2005, their market share likely didn’t have much to do with it being used to treat Schizophrenia.
This email response
to a researcher who was requesting funding from Zeneca
several months after the F.D.A.’s approved Seroquel
might seem odd or even Machiavellian to a Basic Scientist, a Practicing Clinician, or a patient-to-be, but if your business is selling the product, it makes perfect sense:
had poured years and a lot of money into getting their drug approved. Now it was time to focus on reaping the benefits of their hard work. This email mentions Seroquel
‘s starting place – Clozaril
[Clozapine]. Clozapine was the first Atypical Antipsychotic. It had been around for decades. It is a potent antipsychotic that has less neurotoxicity [EPS or Tardive Dyskinesia] than the first generation neuroleptics, but has other big problems – weight gain, Diabetes, and Bone Marrow toxicity [Agranulocytosis] which can be fatal. Schizophrenia can be a malignant disease. The early name was Dementia Praecox, and one of the characteristics was an early death. In some patients, Clozapine works when all others fail, and in an intensely suicidal or catatonic patient, the risks are offset by the potential gain. So the drug is available with strict monitoring of the Bone Marrow status – rarely used. But Clozapine has remained the marker – a drug with less neurotoxicity and potent antipsychotic prowess. Thus, it has been the force propelling the development of the Atypical Antipsychotics – searching for a "safe Clozapine." The fact that there is
a more potent drug is a beacon for researchers to find one that can be used safely, and routinely.
In 1997, Zeneca now had a new drug [derived from Clozapine] that was less neurotoxic, and not toxic to the bone marrow, but as we now know had some of Clozarpine’s other downsides [weight gain and Diabetes], and was not a particularly potent antipsychotic. So Zeneca had a challenging marketing task ahead of them…
Flash: This just in [hat tip to Martha]:
AstraZeneca Plc agreed to pay $150 million to settle more lawsuits claiming its antipsychotic drug Seroquel causes diabetes, pushing the amount the drugmaker has paid to resolve cases over the medicine to almost $350 million, people familiar with the accords said. AstraZeneca, the U.K.’s second-biggest drugmaker, will resolve about 6,000 cases alleging the company knew Seroquel could cause diabetes and failed to adequately warn patients, two people familiar with the settlements said. They spoke on the condition of anonymity because they weren’t authorized to speak publicly about the accords. The cases settled for an average of about $25,000, the people said.
The settlements signal AstraZeneca is seeking to put the Seroquel litigation behind it as it works to overcome setbacks in its drug-development pipeline, said Jeremy Batstone-Carr, London-based analyst for Charles Stanley & Co., who rates the drugmaker’s shares as “accumulate.” “Legal cases represent one of the great imponderables that can act on shareholder sentiment,” Batstone-Carr said. “You try to clear the decks and get investors as great a degree of certainty as possible.”
The settlement, which resulted from a court-ordered mediation, leaves AstraZeneca now facing only about 4,000 Seroquel claims, the people said. The London-based drugmaker announced last summer it had resolved about two-thirds of the 26,000 suits over the drug that had been filed in courts around the U.S…