When EMA and FDA decisions conflict: differences in patients or in regulation?
BMJ 2013; 347 doi: https://doi.org/10.1136/bmj.f5140 (Published 22 August 2013) Cite this as: BMJ 2013;347:f5140
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Me thinketh the good Doctor Wolfe protesteth too much. He builds a straw man of FDA “malleability” with regards to recently approved diet drugs and then proceeds to kick the stuffing out of the straw dummy using statements that do not fully represent the actual data underlying one of the drugs.
Yes, Belviq (lorcaserin) was recently approved. After two thorough FDA reviews followed by the DEA reviewing, in a very deliberative process, and classifying Belviq as Schedule IV – the next to the lowest category for risk of abuse. For perspective on that classification – cough syrup with no more than 200 mg of codeine per 100 grams is Schedule V. Contrary to what Dr. Wolfe suggests, neither the FDA nor the DEA would have signed off on Belviq if they did not think it safe.
The good Doctor cherry-picks some statements from one advisor on the FDA committee that recommended approval of Belviq and kicks away at his straw man. This advisor, of previously questioned objectivity on Belviq approval, stated something akin to “There probably is not sufficient data to absolutely rule out some conditions that might, maybe, possibly be related to the use of Belviq.” An educated man like Dr. Wolfe knows that “proving negatives” is a tough standard to meet, and subjects in the clinical trials took Belviq for two years without any statistically significant evidence of damage to the heart valves that Dr. Wolfe so wants to rip from his straw man. The pharmaceutical company went the extra mile in running comprehensive clinical trial procedures (echocardiographs) to ensure the likelihood that heart valve problems were not an issue. Further, Dr. Wolfe is a physician making statements at odds with the medical literature “In 3 prospective placebo-controlled trials with integrated data for 5249 patients, the rate of echocardiographic valvulopathy was similar with lorcaserin and placebo (Circ Circ Cardiovasc Imaging. 2013 Jul 1;6(4):560-7).
The European Medical Agency, Gallant to the FDA’s Goofus in Dr. Wolfe’s world, cited concerns about the potential for psychiatric disorders such as depression in not giving Belviq it’s stamp of approval. Both the EMA and Dr. Wolfe are wrong on this data as well. Consider the population under study in the clinical trials – the morbidly obese and the severely overweight with at least one co-morbidity. Does Dr. Wolfe wonder if the obese have anything to be depressed about before they ever start a clinical trial? With a slightly higher rate of depression reported by subjects in the Belviq group over the depression rate already occurring at a base level among the obese in the control group, one cannot be fully certain that it did not come about by chance or by some third factor. This is not a healthy population to begin with. Carrying around all that weight can and does affect both your psyche and your heart. The clinical trials, and anecdotal evidence in the three months since approval, indicates Belviq allows people to lose weight, in a safe, gradual, psychiatrically-safe manner.
Sensing that the handfuls of "too-risky" straw laying at his feet is not enough, Dr. Wolfe jabs his dummy over its lack of efficacy. If Dr. Wolfe was as informed as I would think one should be if they are going to disparage a novel drug that can literally help millions of people with a life-threatening condition, he would understand from the data that Belviq does not work for everyone. That’s right – only 40 to 60% of the trial subjects lost substantial weight. (Which of course lowers the overall efficacy rate among all trial subjects that Dr. Wolfe decries.) And that is why the FDA has stipulated that if patients don’t respond within the first twelve weeks of treatment with Belviq, they should not continue on that regimen. If the patient responds by losing a minimum of 5% of their weight in the first three months they get to continue. If the patient doesn’t lose 5%, then they quit taking Belviq and then perhaps Dr. Wolfe and/or the EMA will reveal their secret therapy that will help mitigate the serious medical conditions associated with the disease of obesity. Conditions like diabetes, about which Dr. Wolfe fails to tell his readership that Belviq also combats by, independent of weight loss, significantly lowering HbA1c levels, in many cases greatly lessening the need for insulin.
It is easy to tear apart a straw man of your own making – it is a much more difficult to tackle an obesity epidemic.
Competing interests: I have a small investment (less than 15K USD) in the company that makes Belviq which explains why I have been scrutinizing this drug data and its maker for almost four years).
FDA: the approval of diet drugs and the Mimolette ban.
Wolfe wonders why the European Medicines Agency (EMA) and US Food and Drug Administration (FDA) decisions on drugs conflict. He suggested that FDA which has recently approved two diet drugs is poorly resistant to the drug industry’s desire to get approval for drugs with unique risks.
FDA is not worse than other. All governmental agencies exhibit porosity to the industry interests which depends on whether it is a national industry or not.
I note that lorcaserin and the combination phentermine plus topiramate are marketed by US companies. Similarly, sibutramine, from Abbott an American global pharmaceuticals, was banned first by the EMA. The FDA exhibited a morbid inertia. More than 160 000 prescriptions were filled in the US between 1/10 EMA ban and 10/10 FDA ban.(2)
In contrast, Servier is the French company which owns the patents for fenfluramine (marketing authorization in France in 1965 and in the US in 1973), and dexfenfluramine (1985 in France and in the US in 1996). After the US withdrawal due to reports of heart valve disease and pulmonary hypertension in 1997, both were also withdrawn from other markets around the world, with one exception. France regulatory agencies allowed the marketing of benfluorex, a derivate of fenfluramine, and reimbursed it under the mandatory health insurance scheme until 2009.(3)
The FDA is not different but it advances unmasked. Mimolette, a French cheese, has been outlawed in the US by the FDA since May 2013. Some people say it is a retaliation to prevent the Europe from banning US gmo food exports.
1 SM Wolfe. When EMA and FDA decisions conflict: differences in patients or in regulation? BMJ 2013; 347
2 SM Wolfe. Testimony at the FDA Public Hearing on REMS Standardization
and Evaluation: July 26, 2013.
3 Braillon A. Mediator: who's to blame? Lancet 2011;377:2003-4.
Competing interests: No competing interests
Re: When EMA and FDA decisions conflict: differences in patients or in regulation?
The ostensible differences between the EMA (Europe) and the FDA (US) are superficial and trivial. In reality, these “differences” are a distinction without a difference, because both regulatory agencies have a consistently cozy relationship with Big Pharma, as evinced by the priciness of pharmaceuticals, the prevalence of polypharmacy, and a lucrative revolving door. To quote the Roman satirist Juvenal, “Who will protect us from our protecters?”
Competing interests: No competing interests