Patients taking Effient had a 43 percent higher rate of solid tumors, excluding some skin cancers and brain tumors, than those who received Plavix, according to the analysis of previously unpublished data that appeared today in the Archives of Internal Medicine. The rate of solid tumors, other than brain and some skin cancers, was 1.4 percent of Effient patients compared with 0.9 percent of those on Plavix.
Indianapolis-based Lilly is counting on Effient to replace lost revenue after its top-seller, the antipsychotic Zyprexa, faces generic competition in 2011. However, initial sales of the drug have been “disappointing,” wrote Christopher Schott, a pharmaceuticals analyst at JPMorgan Chase Bank, in a note today to investors today. Effient pulled in $29 million in revenue last year. Plavix, the world’s second-biggest selling medicine, generated $9.5 billion in global sales for New York-based Bristol-Myers and Paris-based Sanofi-Aventis SA.
“Some of the enthusiasm for the drug has already worn off, but this is very concerning,” said James Floyd, a postdoctoral fellow in cardiovascular health at the University of Washington in Seattle and one of the paper’s authors, in a telephone interview. “The main message to the FDA is, let’s make sure this thing doesn’t cause cancer if you’re going to keep it on the market.”
The analysis looked at data from a trial called Triton-Timi 38 that had been submitted to the U.S. Food and Drug Administration as Lilly applied for approval to sell Effient.
Victor Serebruany, the paper’s second author and an adjunct professor at Johns Hopkins University in Baltimore, was involved in early studies of the drug and was paid for a related patent, according to his disclosure that accompanied the research. Serebruany criticized the Triton study in a June 2009 editorial in the journal Cardiology.
“The hypotheses by Serebruany have been previously presented and published as well as reviewed, discussed at length and addressed by the U.S. Food and Drug Administration,” Lilly said in a statement released today in response to the analysis. “The FDA concluded that a causal link was unlikely.”
Effient received U.S. clearance in July 2009 for use in preventing blood clots in people getting angioplasty to repair or unblock blood vessels. The Triton study found the Lilly drug reduced cardiovascular deaths, heart attacks and stroke by 19 percent compared with Plavix.
Effient works by preventing blood platelets from sticking together, activity that may help explain the cancer link, Floyd said. Platelets provide “natural defenses against tumor growth” by trapping tumor cells in blood vessels and helping them stick to vessel walls.
The 16-month duration of the study suggests Effient didn’t trigger new cancers because that process usually takes longer, the authors wrote. Instead, the medicine probably led small or contained cancers that were already present to grow, the report said.
FDA officials were aware of a potential association between Effient and cancer at the time the drug was approved, Floyd said. Thomas Marciniak, an FDA medical reviewer, performed a detailed analysis of adverse events including solid tumors. Agency reviewers disagreed about what types of cancers should be counted and whether the higher incidence seen with Effient could be due to chance, Floyd said.
In a January 2009 staff review outlining the rationale for that decision, Ellis Unger, deputy director of the FDA’s cardiovascular products division, wrote that the agency was “lacking definitive data” regarding cancer risk.
An editorial accompanying today’s report urges further study, adding that the postmarketing trials the company is required to run aren’t large enough to rule out a cancer link.
“Sufficient credible evidence has emerged to raise concerns about a potential risk,” wrote Sanjay Kaul, a cardiologist at Cedars-Sinai Medical Center, and George Diamond, a cardiologist at the University of California, Los Angeles. Until further study is done, they recommend that Effient use should be limited to “weeks rather than months.”