Lilly’s Effient steps forward, then back

Eli Lilly and Co. just can’t catch a clean break on its newest drug, the blood thinner Effient. A day after doctors
were alerted to a black-box warning that could slow sales of Effient’s main competitor, Plavix, a medical journal published
research showing that patients suffered 43-percent more cancer tumors on Effient than on Plavix.

Plavix is the leading blood thinner. Its makers, New York-based Bristol-Myers Squibb Co. and France-based Sanofi-Aventis
SA, raked in $9.5 billion in sales from the drug last year.

Effient, by contrast, has recorded just $35 million in sales during its first three quarters on the market. At one time,
investors hoped Effient would save Indianapolis-based Lilly from its looming raft of patent expirations, but their ardor has
chilled substantially.

Lilly executives have remained upbeat about Effient, saying it’s the kind of drug that must receive a complex series
of approvals from hospitals, insurance companies and the government-run health plans of European countries. As it does so,
they predict, sales will increase.

Effient is approved for use only in patients undergoing hospital-based procedures, such as the implanting of stents. Lilly
hopes its ongoing clinical trials of the drug allow Effient to be used in more settings in the future, as Plavix is.

The black-box warning about Plavix, ordered in March by the U.S. Food and Drug Administration, was detailed Monday in an
alert issued by the American Heart Association and the American College of Cardiology Foundation. The drug cannot be metabolized,
or broken down, by some patients, so the medical groups made three main recommendations to doctors, including a suggestion
to consider Effient.

“Realize that there are other drugs out there that are alternative,” the alert read. “Prasugrel [the chemical
name for Effient], for example, is one option, but its benefits must be weighed against its bleeding risks.”

Effient has been controversial since Lilly and its development partner on the drug, Japan-based Daiichi Sankyo Co. Ltd.,
announced results of a head-to-head trial against Plavix in November 2007. Effient reduced by 19 percent patients’ incidence
of heart attacks and strokes compared with Plavix, but also increased bleeding and fatalities from bleeding.

It took the FDA a year and a half to untangle those complex results before it approved Effient last August. The FDA gave
the drug a black-box warning for its bleeding risk.

One of Effient’s strongest critics, Dr. Sanjay Kaul, was excluded from the FDA’s review committee after Lilly
complained that he was biased.

Now, as the Archives of Internal Medicine published a study Tuesday documenting the higher rate of tumors in patients
taking Effient, Kaul renewed his warnings about Effient.

“Sufficient credible evidence has emerged to raise concerns about a potential risk,” wrote Kaul, a cardiologist
at Cedars-Sinai Medical Center, and George Diamond, a cardiologist at UCLA, in an editorial in the Archives of Internal
Medicine. According to Bloomberg News, they recommended Effient be used only for weeks, not months, until further research
is done.

But Lilly and Daiichi answered that the cancer risk was examined and dismissed by the FDA reviewers of Effient. In a statement,
the two companies said, “It is important to note that the hypotheses [about Effient’s cancer risk] have been previously
presented and published as well as reviewed, discussed at length and addressed by the U.S. Food and Drug Administration.”