The drug for memory loss
Posted by medconsumers on April 21, 2012
“Is it simple memory loss? … Or is it Alzheimer’s disease?” This was the headline—over the photo of a worried adult—for a pervasive drug ad of yore. It sent chills up the spines of many a middle-aged and older person. Aricept, a drug for Alzheimer’s disease, quickly became a blockbuster in the U.S. to the tune of $2 billion in annual sales. All the more amazing, considering that Aricept is barely better than a placebo. Well before Aricept’s patent would expire, the company in charge of marketing had to come up with a plan for keeping profits high while fending off generic competition. Pfizer’s plan was simple—just increase the drug’s dosage. Same useless drug, but a new improved dose!
The story of how Pfizer and Eisai, the company that developed Aricept, managed to pull this off was laid out in last month’s issue of the British Medical Journal. I confess that when the co-author of this paper sent me a copy, I thought for a minute that I was reading satire (British publications have that effect on me). Somehow I had missed Aricept’s higher-dose ad campaign.
What makes this especially appalling and different from the usual ineffective-drug-makes-billions story, is this: Aricept is for people with a particularly devastating disease whose treatment decisions are usually made by the patient’s relatives who are often desperate for anything that might work.
Approved only months before Aricept was to lose its patent protection at the end of 2010, “The ‘new’ 23 mg product would become patent protected for three more years,” wrote Lisa M. Schwartz, MD, and Steven Woloshin, MD, both of the Center for Medicine and the Media at the Dartmouth Institute for Health Policy and Clinical Practice, Lebanon, New Hampshire, with a long and impressive history of activism on the topic of misleading drug ads. Why 23 mg? Answer: Aricept is now available generically (donepezil), but only in 5 mg and 10 mg doses, and there’s no way these two doses can add up to 23. Got it?
Initially, the U.S. Food and Drug Administration required the higher dose be proven superior to the 10 mg dose. Eisai, Aricept’s manufacturer, agreed to the FDA’s demand that this be shown for both cognitive and overall functioning. The pre-approval trial of 1,400 patients barely showed improvement in the former and failed completely on the latter. Yet Aricept 23 mg received the FDA’s approval anyway.
Drawing from the FDA’s own publicly available documents, Drs. Schwartz and Woloshin found that Aricept 23 mg had been approved over the objections of the FDA’s medical and statistical reviewers. Russell Katz, director of the FDA’s Division of Neurology Products, who initially required the higher dose be proven superior on two measures, inexplicably, chose to reverse himself. “In my view, this strongly argues for a conclusion that the 23 mg does is very likely to also have an effect on overall functioning, despite this not having been demonstrated directly in this study…I believe that the sponsor has demonstrated that the 23 mg dose of Aricept is effective…I will approve this application.”
Russell Katz also went on record ignoring his own alarming assessment of the 1,400-person pre-approval trial: “There is a clear increase in the incidence of adverse events on the 23 mg dose compared to the 10 mg dose…These are not trivial events; in these patients, these could lead to significant morbidities and even increased mortality.”
All Pfizer and Eisai needed from then on was an immense marketing budget. Nurse educators were sent to the heavy-duty prescribers—neurologists at high-volume long-term care facilities. The sales pitch: “There are no ‘stable’ Alzheimer’s disease patients—therefore aggressive treatment is required.”
The Aricept 23 mg ads aimed at consumers relied primarily on visuals—shots of loving caregivers with a spouse or parent with Alzheimer’s disease and this implied message: Truly caring people would ask their doctors for Aricept 23 mg for their loved ones. The ads say that the drug improves cognitive symptoms but not overall functioning, wrote Drs. Schwartz and Woloshin. “But there is no explanation of why that matters.” Side effects are mentioned without any information about how serious or frequent they can be.
The ad aimed at doctors is worse, according to Drs. Schwartz and Woloshin, because it contains “a stunningly erroneous statement in a large bold font: ‘Patients on Aricept 23 mg/day experienced important clinical benefit on both measures [cognitive and overall functioning]’. “Worse, this statement is directly contradicted in smaller plain font that says ‘the results for global function did not show statistical significance’.”
Drs. Schwartz and Woloshin were shocked to find that this erroneous statement also appears on the Aricept’s label [the detailed information aimed at health professionals], “This study showed that patients on 23 mg per day experienced important clinical benefit on both cognitive and global measures (overall functioning).
Will the two companies get away with the deceptions? The stats are only just coming in. More than 68,000 prescriptions were written for Aricept 23 mg in the first six months after approval. The only bright spots in this saga are Drs. Schwartz and Woloshin, who have outdone themselves in exposing this particularly cruel drug industry deception. They have perfectly illustrated the M.O. for many big drug companies: Why waste money developing a drug that actually works when profits can stay steadily high with one that doesn’t?
Maryann Napoli, Center for Medical Consumers©