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.