The Show Ain’t Over Till the Fat Lady Sings

By Johanna Ryan

As 2015 dawns, the specter of Corporate Personhood, sanctified by trade treaties which put patents and profits above the needs of us humans, seems to be drawing ever closer. Our latest wake-up call came from the respected French drug safety journal Prescrire. They’re sounding the alarm about a December 19 vote by the EU’s Committee on Medicinal Products for Human Use (CHMP) to approve an expensive, hazardous weight-loss drug called “Mysimba”.

A bit of history: Last fall RxISK joined consumer groups across the European Union, including Prescrire, to protest a proposal (thankfully defeated for now) to give the Department of Enterprise and Industry power over drug safety. This proposal was seen by many as linked to the proposed Transatlantic Trade and Investment Partnership (TTIP). TTIP, along with its sister Trans-Pacific and EU-India trade treaties, would allow corporations to challenge a wide range of national laws in the name of “free trade.” That most definitely includes regulations aimed at restricting the sale of useless and dangerous drugs.

At the time we pointed to the European Medicines Agency’s rejection of two weight-loss drugs that had been approved by the U.S. FDA: Belviq (lorcaserin) and Qsymia (a combination of the stimulant phentermine and the anticonvulsant topiramate). The EMA had done the right thing, we said. These drugs carry a known risk of heart attacks, strokes and cardiac damage – much like Redux, Fen-Phen and Meridia, earlier diet drugs taken off the market after patients died.

As if that’s not enough, both lorcaserin and topiramate are known to trigger serious mental reactions in some patients, from memory loss to suicide. In exchange for all this risk, both drugs had narrowly cleared the FDA’s very modest hurdle of a 5% average weight loss. Five percent! And both required long-term, even lifetime use to keep the weight off.

Can you imagine a world where your national health service would be forced to put these drugs on the menu, we asked, just because they’d been approved in the US?

We can imagine just this, but then we can even imagine a world where a national health service disappears, sold off to the highest bidder. UK unions have demanded that health care be taken off the table in the TTIP talks, warning that for-profit contractors could crush any effort to limit further privatization of the NHS, or reverse the damage already done.

Weighty risks and lightweight rewards

So is Mysimba, or Contrave as it’s known in the US, an improvement over the drugs rejected last year? Hardly. If anything, it’s worse. Like Qsymia, it’s simply a patented combination of two older, off-patent drugs, allowing its maker to reap large profits without inventing anything new.

The first of these is bupropion, a stimulant known in the UK as the stop-smoking aid Zyban. In the US it’s widely prescribed as an antidepressant (Wellbutrin),[1] and its tendency to raise blood pressure and heart rate is well-known. Many people find it makes them anxious and irritable, and more than a few find things get a lot worse than this. The FDA has linked it with a high degree of probability to 1,793 suicides and ten homicides.

The usual adult dose of Wellbutrin is 300 mg, Contrave’s recommended dosage includes a bracing 360 mg of bupropion.

The second Contrave ingredient is naltrexone, used to help heroin addicts quit by blocking the pleasurable effects of opiates. Naltrexone has its own side-effect profile, including nausea, vomiting and insomnia. While bupropion, like other stimulants, is an appetite suppressant, there’s little basis for thinking naltrexone will reduce the rewards of sweets or otherwise help dieters. Contrave was approved using the same 5% weight loss standard the FDA applied to Qsymia and Belviq.

The skinny on obesity

Contrave’s maker, Orexigen, and its marketer, Takeda, have mobilized experts to declare that obesity is a public health crisis which demands treatment. It’s linked to heart disease, diabetes and other ills; it plays some role in cancer; and serious obesity is on the rise. All true. Yet how much will the seriously obese benefit from a drug that produces perhaps five percent weight loss, while putting their already over-stressed hearts at greater risk? For a 5’4”, 250-pound patient, a 5% loss will get you down to 237.5 pounds. A terrific result, twice as good as average, would still only take you to 225 pounds. And remember, that’s in conjunction with faithful dieting and exercise.

The drugmakers know this – which is why they’re also targeting people whose excess pounds are not a medical crisis. Contrave, like the others, is approved for patients with a Body Mass Index of 30 or more, OR those with a BMI of at least 27 and one obesity-related condition such as high cholesterol, high blood pressure or diabetes. A 5’4” Diva (or Divo? – perhaps Divan if overweight) who weighs just 157.5 pounds is a case for Contrave if her last cholesterol reading was 210.

Any sane doctor would advise our Diva to eat sensibly and stay active, but not to obsess about her weight or her cholesterol number. She certainly doesn’t need to risk a laundry list of new health problems – perhaps even voice loss – for the sake of an eight-pound weight loss.

Does FDA read its own leaflets?

Industry analysts expect Contrave to outstrip the modest sales numbers generated so far by Belviq and Qsymia. The main reason: Takeda is putting an expanded sales force of 900 or more at Contrave’s disposal – and Takeda, thanks to its diabetes drug Actos, has enviable contacts in the “diabetes community” where so many doctors who treat obese patients can be found.

This makes me wonder: Does the FDA read its own literature? Its official prescribing information says that bupropion carries a dose-dependent risk of seizures, and “should be administered with extreme caution to patients with a history of seizure, cranial trauma, or other predisposition(s) toward seizure.”

Among the “other predispositions” it lists are heavy use of alcohol or sedatives; use of a dizzying variety of other drugs (including antidepressants) that lower the seizure threshold; and … “diabetes mellitus treated with oral hypoglycemic drugs or insulin.” In other words, exactly those patients expected to give Contrave its market advantage.

But wait, there’s more. I checked Contrave’s ingredients – bupropion and naltrexone – for drug interactions on two websites (RxISK.org and Drugs.com) that use FDA-provided content. Lo and behold, both advised I should “Generally Avoid” this combination! Why?

“The use of naltrexone with other potentially hepatotoxic [liver-damaging] agents should be avoided whenever possible.”

That includes bupropion, as well as acetaminophen, NSAID painkillers like ibuprofen, and cholesterol-lowering statins – another class of drugs Contrave’s target market is highly likely to be using.

As for opiate painkillers: If you’re taking naltrexone, a small dose of opiates will merely be ineffective. A large dose, however, could bring on a severe and possibly even fatal withdrawal reaction. If you are in a serious accident while on this drug, and need to be rushed to the hospital for a stiff dose of morphine, you could be in big trouble. The FDA advises you to carry a card informing medics you’re taking naltrexone, just in case. Will Contrave patients get the same advice?

Whose health and welfare?

Why on earth would any regulator, anywhere, allow a drug like this on the market? The answer may depend on whose health and welfare they’re trying to protect.

Last year RxISK took part in another drug-safety campaign, this one by activists in the US who are trying to halt the epidemic of prescription opiate addiction. This epidemic now claims about 16,000 lives per year. If the new diet drugs are a pox that Europe would be better off without, the US opioid epidemic is something Europe should quite literally avoid like the plague.

According to the Centers for Disease Control, it has its roots in relentless over-promotion of these drugs for chronic non-cancer pain, which has led to massive overprescribing. Yet fifteen years into this epidemic the FDA continues to approve new patented formulations of these very old drugs – including, in late 2013, a high-dose, extended release hydrocodone pill called Zohydro. With a month’s supply of Zohydro selling for over $400, compared with about $25 for older hydrocodone pills, you can bet it will be aggressively promoted.

Here’s how an FDA official explained to shocked scientists and activists why it was giving Zohydro the green light:

They knew it “would contribute to the already critical public-health problem of prescription opioid abuse”, but they felt the FDA could not “punish this company and this drug because of the sins of the previous developers and their product.”

Apparently, if Purdue Pharma had gotten its shot at creating a public-health disaster with OxyContin, then the makers of Zohydro deserved their chance too.

In other words, the corporation has a right to live and thrive which may trump your own, or that of your children. If you shouldn’t take Contrave for your own health, maybe you should take it for Takeda’s!

Apparently the same world view has now taken root at the European Commission as well. No doubt Alkermes Ltd., which thus far has not even applied to sell Zohydro in the EU, will take heart. If this is where things stand without a Transatlantic or Trans-Pacific trade pact, what can we look forward to if they are ratified?

Getting the Fat Lady to lose some but not too much weight is a way to keep the show on the road forever.

[1] It’s not the first time bupropion has been promoted for weight loss. In a marketing campaign memorably dubbed “Operation Hustle,” Glaxo Smith Kline promoted Wellbutrin off-label for obesity and sexual dysfunction, informally branding it as “the happy horny skinny pill.” GSK’s illegal marketing of Wellbutrin, along with its off-label promotion of Paxil for children and teens, led to its record-breaking $3 billion payment in 2012 to settle criminal charges in the U.S.