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Big Pharma Baffled Again

The latest federal study of schizophrenia drugs holds as many questions as answers.

Updated from 10:20 a.m. EDT

For the second time in six months, a federally financed study of schizophrenia drugs has offered no clear signal to investors about what drug might make the biggest gains and which company could stand to benefit the most.

Like the first round of testing, the latest set of data show that the most effective drugs for a disease that affects 3.2 million Americans often have the most side effects.

Doctors' prescribing patterns don't appear to have been significantly affected by the first round of results, and months will need to pass to determine whether the new results will affect the sales of drugs known as atypical antipsychotics.

"There is no clear 'winner' among the second generation of antipsychotics, weighing effectiveness and efficacy against side effects, nor a clear 'loser,'" says Dr. Carol A. Tamminga, professor of psychiatry at the Southwestern Medical Center in Dallas.

Her comments, published in the April issue of the

American Journal of Psychiatry

, accompany two studies funded by the National Institute of Mental Health. The studies are part of a comprehensive review of schizophrenia medicines, known as the Clinical Antipsychotic Trials for Interventions Effectiveness, or CATIE.

Since the studies didn't have corporate funding, CATIE "increases our confidence that they are as free from marketing or other bias or 'spin' as possible," Tamminga says.

Massive Market

Starting with 1,460 patients, the study is comparing numerous drugs during 18 months of treatment. By contrast, company-sponsored tests are much shorter, enroll a narrow range of patients and only examine one or two drugs at a time, says the National Institute of Mental Health.

Brand-name schizophrenia drugs produced more than $9 billion in sales last year, and CATIE analyzed medications from

Eli Lilly

(LLY) - Get Free Report


Johnson & Johnson

(JNJ) - Get Free Report



(PFE) - Get Free Report



(NVS) - Get Free Report



(AZN) - Get Free Report


For investors, "we currently do not foresee a major shift in prescription trends arising from the study results," says a recent report from Sagient Research Systems, a San Diego firm that tracks pharmaceutical trends.

The results from the

first round of CATIE research, comparing four newer products with the older, now-generic perphenazine, weren't exactly what scientists had been expecting.

Surprisingly, perphenazine "was as well tolerated as the newer drugs and was equally effective as three of the newer medications," researchers said of the study that was published in

The New England Journal of Medicine

. "Contrary to expectations, movement side effects -- rigidity, stiff movements, tremor and muscle restlessness -- primarily associated with the older medications, were not seen more frequently with perphenazine ... than with the newer drugs."

Perphenazine was compared with Lilly's Zyprexa, Pfizer's Geodon, AstraZeneca's Seroquel and J&J's Risperdal. Researchers said Zyprexa outperformed its peers as well as the generic drug, but its benefits "were modest and must be weighed against the increased side effects."

Zyprexa users stayed on their medication longer and were less likely to be hospitalized for a psychotic relapse. However, they had higher rates of weight gain and diabetes.

Some analysts had speculated that Zyprexa might benefit from the study, but instead its U.S. prescriptions continue to slip, according to IMS Health, an industry sales tracker.

"Declining U.S. Zyprexa demand has so far failed to respond to CATIE results, though we note it's still early," Richard Evans of Sanford Bernstein wrote in a recent research report.

Evans says Zyprexa's weekly market share of new prescriptions has been declining since the first CATIE results were published. Evans, who has a market perform rating on Lilly, doesn't own shares. His firm doesn't have an investment-banking relationship.

Not Perfect

The first CATIE study also surprised the National Institute of Mental Health. Just because perphenazine's price is one-tenth that of newer drugs, the institute says, doctors and insurers shouldn't automatically select the generic drug as a first treatment. "To say the medications are equivalent is not to say they are identical," the institute says. "Individual patients may have responded far better to one of the available drugs."

In a few months, another CATIE study will examine issues affecting reimbursement. "Cost effectiveness is more than a comparison of medication costs," the institute says. "Differences in the rates of hospitalization

and use of support services" plus other factors must be considered.

The first CATIE study had a high dropout rate, either because drugs didn't work or because they triggered severe side effects. Three-quarters of the patients stopped taking their drugs before the 18-month test had ended.

In the second round, the dropouts who agreed to stay in the CATIE study received another drug, but perphenazine was excluded. CATIE's guidelines had been set long before the generic drug produced such unexpected results, the National Institute of Mental Health says. Thus, CATIE can't assess if older drugs are good follow-up choices when patients discontinue newer drugs.

One study of 99 patients in the second round included Clozaril from Novartis, which the institute says is "more effective" than other drugs in controlling psychotic symptoms. The median time patients stayed with Clozaril was 10.5 months, whereas the median times for the other drugs didn't exceed 3.3 months. However, Clozaril can cause vicious side effects, such as "life-threatening blood and heart complications."

Researchers said safety monitoring is necessary to detect any side effects. Because of the potential for problems and the monitoring requirements, some patients might be discouraged from trying the drug even though it might be helpful, the National Institute of Mental Health says.

The second round also included a test in which 444 patients were given Zyprexa, Seroquel, Geodon or Risperdal. The study said Risperdal and Zyprexa were, on the whole, more effective than Seroquel and Geodon. The median time for staying on Risperdal was seven months, followed by Zyprexa (6.3 months), Seroquel (four months) and Geodon (2.8 months). Improved effectiveness, rather than reduced side effects, was the reason patients responded more favorably to Risperdal and Zyprexa.

Although CATIE was designed for doctors and patients rather than for investors and analysts, the results leave a gap in comparing the drugs. Abilify from

Bristol-Myers Squibb

(BMY) - Get Free Report

was excluded because it wasn't approved by the FDA when the study was designed.