The very first page of this book begins with the prose equivalent of a clean right to the jaw: a graphic account of the bloody death of cancer patient Jim Lenox, hours after being injected with Amgen's and Johnson and Johnson’s blockbuster drug, Procrit. One thing is for sure: author Kathleen Sharp isn’t playing. After finishing this meticulously researched book, even the most cynical reader is likely to shake his head and think, My God, it’s even worse than I thought.
Procrit is a trade name for epoetin alpha, a synthetic version of a naturally occurring protein synthesized by the kidneys which stimulates the production of red blood cells. Scientists at Applied Molecular Genetics, or Amgen, discovered the gene for this protein and in 1984 patented a process for producing epoetin alpha (or epo, as the generic version came to be known) from hamster ovaries.
Amgen had a potential blockbuster drug on its hands. The AIDS epidemic was sweeping the country. At the time there was no way to detect HIV-tainted blood, and any new drug which reduced the need for blood transfusions could have had the potential to save untold numbers of lives. But Amgen needed capital to develop their new drug, and they entered into a partnership with staid industry giant Johnson and Johnson. Under their product licensing agreement, J & J had exclusive rights to market epo in Europe plus exclusive rights to all markets in the United States except for dialysis patients.
Epogen, Amgen’s version of epo, was approved by the FDA in 1989. J & J’s version, Procrit, was approved in 1992. The FDA decided that safety studies could be done after the drug was brought to market, a decision that made no sense. To be sure, in 1984 there was a crying need for a drug which could reduce the need for blood transfusions and thus the risk of contracting AIDS, but by 1989, that was a moot point. The blood supply was safe. We will return to this point later.
Since dialysis patients are not segregated from other kinds of patients, the product licensing agreement between Amgen and J & J was basically an open invitation to both sides to cheat like crazy, by poaching on each other’s turf as much as possible. Soon the two supposed partners were locked in a protracted legal battle.
J & J also launched an all-out effort to sell as much Procrit as possible to its legitimate market, which was non-dialysis patients. Besides dialysis patients, the only FDA-approved indication for epo was for cancer patients currently undergoing chemotherapy. While physicians have wide latitude in prescribing almost any drug for almost any condition, the law strictly prohibits off-label marketing of prescription drugs by drug companies. J & J set about trying to circumvent this prohibition by any means necessary.
Some incredibly slapdash studies were cobbled together, with vaguely defined endpoints – “improved quality of life,” “less fatigue,” etc. Very often, the docs who were paid to conduct these studies couldn’t be bothered to do the work of selecting patients for the study and collecting data themselves, instead fobbing these tasks off onto drug company reps. This was a blatant violation of patient confidentiality laws, but the drug company reps were only too happy to comply.
Taking advantage of the good old American “more is better” mentality, drug company reps urged doctors to inject patients with doses of Procrit far in excess of approved guidelines, all the while assuring them the drug was “as safe as mother’s milk.” Doctors were also wooed with speaking fees, consulting fees, research stipends, grants, rebates, free meals, and “continuing education” seminars at luxury resorts where, in between rounds of golf, they could watch PowerPoint presentations based on the bogus studies. Meanwhile, the airwaves were saturated with J & J’s “Strength for living” ads for Procrit. The “Fatigue Coalition,” a “patient-advocacy group” financed by J & J, promoted the off-label use of the drug.
Oncologists bought Procrit in bulk and billed insurers the retail rates. One J & J salesman remarked, “Every oncologist in Tucson is a millionaire because of Procrit.” Even more outrageously, hospitals and clinics were plied with free samples of Procrit and encouraged to bill Medicare – again, a blatant violation of the law, but nobody seemed to mind.
Mark Duxbury watched all of this unfold. Duxbury was a frustrated would-be medical doctor and rising star at J & J. As a youth, he wanted to study premedicine but his father threatened to cut him off financially unless he majored in music (isn’t it supposed to be the other way around?). After graduating from the University of Washington, he took a sales job at SmithKlineBeecham and in 1992, he landed a position at J & J’s newly formed biotech division, Ortho. Duxbury was based in Seattle, Washington, but his beat included most of the Pacific Northwest.
Time and again, Duxbury’s superiors set seemingly impossible sales quotas for him, and time and again he exceeded them. But some careless remarks he made while being deposed by an attorney for Amgen sealed his fate. He was forced to resign from J & J, and as a final vindictive little slap in the face, the company blocked his unemployment compensation.
Sharp takes some 200 pages to chronicle, in minute detail, the corporate skullduggery which led to Duxbury’s ouster, along with the marital and financial woes of this modern-day Willie Loman. Then the real fun begins. Duxbury filed a wrongful termination suit against his former employer, and when that went nowhere, he teamed with attorney Steve Berman to file a whistleblower lawsuit in the US District Court of Massachusetts against J & J for Medicare fraud as well as off-label promotion of Procrit.
Meanwhile, the safety data for epo began coming in (more than a decade after the drug was approved by the FDA) and it was bad. It was worse than anyone could have imagined.
Epo was found to promote tumor growth and to increase the risk of blood clots, heart attacks, strokes, and death. A meta-analysis of some 52 studies by Charles Bennett found the drug increased the risk of dying by seventeen percent. Millions of patients have been prescribed this drug. Nowhere in the book could I found an authoritative figure for the number of patients that have been killed by this drug, but Duxbury himself estimated the total to be in the neighborhood of half a million.
Half a million deaths. Imagine having that on your conscience.
Inexplicably, Berman later dropped his client, but then Boston attorney Jan Schlichtman took up the cause. Schlichtman, a six-foot five-inch former competitive swimmer and champion litigator had already risen to national prominence through his lawsuit against W.R. Grace and Beatrice Co., who were accused of poisoning the drinking water of the town of Woburn, Massachusetts – a case chronicled in the movie A Civil Action. Schlichtman won in court, but the protracted legal battle left him burned out and bankrupt. He borrowed the money to buy a one-way ticket to Hawaii and spent some time there as a beachcomber, sleeping under the stars. At one point, he swam out into the Pacific Ocean with the intention of drowning himself, but he changed his mind and turned back. Now he was back in Boston, looking for a new cause to champion.
In January of 2008, Judge Rya Zobel of the US District Court of Massachusetts ruled against Duxbury. Schlichtman took the case to the US Circuit Court of Appeals, which in August of that year ruled in his favor. J & J appealed the case to the Supreme Court of the United States, which declined to hear it and instead kicked it back to the District Court of Massachusetts.
Meanwhile, in December of 2009, the FDA announced new guidelines for epo. Dialysis patients could continue to receive the low doses of the drug, but its use in cancer patients was restricted to those who were expected to live no more than six months.
In September 2010, Judge Zobel issued her ruling: a case involving billions of dollars worth of Medicare fraud from coast to coast was shrunk to seven counts in the Seattle area.
Duxbury never knew about the new FDA guidelines, nor about Judge Zobel’s ruling. On October 12, 2009, he died from an overdose of alcohol, oxycodon, oxcarbazepine, and methadone. Also coursing through his bloodstream at the time of his death were the prescription drugs Lipitor, Tricor, albuterol, diltiazem, digoxin, warfarin, Topiramate, and Trileptal.
While the Department of Justice under Attorney General Eric Holder filed an amicus curiae brief on behalf of Duxbury's whistleblower lawsuit against J & J, they so far have declined to prosecute either J & J or any individual in connection with this case. Author Kathleen Sharp notes that after serving as Deputy Attorney General under President Clinton and before serving as AG under President Obama, Holder worked for the law firm Covington & Burling, advising J & J on whistleblower lawsuits.
Epo remains on the market, with annual sales of $11 billion and cumulative sales approaching the $100 billion mark.
Erythropoietin molecule illustration courtesy of European Bioinformatics Institute