Eli Lilly’s big-selling antipsychotic drug Zyprexa (olanzapine) has had its
labelling changed in the USA to warn that it may be more likely to cause
elevated blood sugar than some of its rivals. The changes also tighten
warnings about its tendency to cause weight gain and raised blood lipids.
The development isn’t expected to put much of a damper on sales of the
olanzapine franchise, as the drug is an important part of the treatment
arsenal for patients suffering from schizophrenia and bipolar disorder. But
observers suggest it could put fire in the bellies of lawyers seeking
damages over side effects claimed to result from the product’s use, as well
as Lilly’s alleged tardiness in highlighting them, and prompt other
claimants to come forward.
Lilly has already paid out over $1 billion to settle tens of thousands of
lawsuits claiming the company failed to disclose health risks associated
with the treatment, whilst steadfastly denying that Zyprexa was at fault. A few hundred cases were still outstanding as of the middle of September.
The latest changes are the result of an ongoing dialogue with the US Food
and Drug Administration about the safety of olanzapine, and have been
prompted by data from Lilly’s in-house clinical trials, as well as
independent studies such as CATIE and CAFE.
Lilly said in a statement that the label now draws some comparisons between Zyprexa and some of its rivals, and includes: “Additional language on a greater association of increases in glucose levels with olanzapine than with some other atypical antipsychotics.”
Previously Lilly has always suggested that Zyprexa was less likely to cause
elevated blood glucose than its competitors, such as Johnson & Johnson’s
Risperdal (risperidone), Pfizer’s Geodon (ziprasidone), Bristol-Myers
Squibb’s Abilify (aripiprazole) and AstraZeneca’s Seroquel (quetiapine). But
the label does not link the use of the drug to the development of diabetes,
something that Lilly still insists is unproven.
Other amendments to the label suggest that Zyprexa can continue to cause weight gain in patients for up to two years – longer than previously
thought. The weight gain is thought to be caused by an increase in appetite and be a feature of all the atypical antipsychotic class.
Despite the negative press about metabolic side effects and ongoing
allegations that the company improperly promoted the antipsychotic for
off-label uses, Zyprexa is still selling well, with second-quarter revenues
up 9% to $1.2 billion, helped by price increases that have offset lower
prescribing rates.
Also affected by the label change is Symbyax (olanzapine and fluoxetine),
which Lilly sells as a treatment for bipolar depression.
Adolescent labelling
Lilly is also hoping to extend the indications of Zyprexa by securing
approval for its use in adolescents, so it is interesting that the new label
makes specific reference to the metabolic changes observed in this age
group. Lilly was sent an ‘approvable letter’ from the FDA in April asking
for more time to review the data in adolescents. J&J’s Risperdal is already
approved for use in this age bracket, while B-MS’ Abilify is currently under
review.
