More than a decade ago, the fen-phen weight-loss cocktail and a related diet pill called Redux made headlines after links to heart and lung troubles forced a recall, which eventually cost Wyeth $21 billion in charges. Other prescription drugs - Abbott's Meridia and Roche's Xenical - never fared well due to side effects. Sanofi-Aventis never soldAcomplia due to psychiatric side effects. And even the over-the-counter Alli pill, which is really a version of Xenical, is suspect these days thanks to concerns over liver injury ( see here).
Now, though, a trio of would-be diet pill makers is focusing attention anew on the long-disgraced obesity market. This is underscored by Eisai's willingness to pay $50 million for the rights to sell Arena Pharmaceuticals' lorcaserin in the US; another $160 million based on development and approval milestones, and a $1.16 billion, one-time payment that may follow based on annual sales. This is a big deal, because Arena is now the first of the threesome to strike this sort of pact with a much bigger partner. In a trial, 47 percent of lorcaserin patients lost at least 5 percent of their body weight, compared with 23 percent on a placebo. Arena, however, may have an advantage over its rivals.
One is Orexigen Therapeutics, which is developing Contrave, a combo of the Wellbutrin antidepressant and a sustained release form of naltrexone, an opioid blocker used to treat addictions. This pill, which showed a 6 percent weight loss in trials, comes up for FDA review in December. And later this month, Vivus faces an FDA panel over its Qnexa pill, which combines phentermine (the part of fen-phen that wasn't fatal) and topiramate, which is sold by Johnson & Johnson as Topamax for treating seizures and migraines. One trial demonstrated nearly 15 percent weight loss.
Obesity, itself, remains a hot topic because of the growing number of overweight people are at risk for various health complications. But weight-loss cocktails that combine existing drugs may be a hard sell, especially if side effects are lurking. The Vivus meeting will almost certainly provide insight into how the FDA believes obesity should be treated. And then there's price. Everyone knows that insurers don't want to cover drugs that may be taken by a gazillion people who could lose a few pounds through other means. "Managed care doesn't want everybody to be on" a diet drug, says Bruce Leavitt, lead payer value consultant at Milliman, "especially not with what's happened in the past."
Nonetheless, one analyst remains bullish on the prospects for FDA approval. In an investor note, Jon LeCroy of Hapoalim Securities, writes the FDA wouldn't have scheduled advisory committee meetings for the drugs "if the FDA viewed the efficacy or safety data clearly warranting not approving the drugs, then there would be no need to host an expert panel." He also believes the panel experts may be inclined toward approval, since they are disposed to be in favor of new therapies. Maybe so, but given the track record, those advisory committees should exercise extra caution.
pic thx to alan cleaver on flickr
13 Comments
As I wrote in my blog on 9th April, 2010, obesity is a BIG business. The most important of all, obesity has a major impact on economy. The treatment/cure business of obesity is huge.
http://krishnaonlifelivingandmedicine.blogspot.com/
Regulators are bogged by issues related to safety of the drugs aimed to reduce obesity. Rightfully so; because misuse, overuse, abuse are the potential risks with these drugs. Hope of anyone following the label for these drugs are is very slim. Factual labels may not work for the drugs aimed at obesity. Makers of these drugs, FDA and other regulators may need to work together and consider different, modified labeling approach in order get some of these beneficial drugs to the market, yet protect the users from safety issues.
I worked in the area of appetitte suppressants in the early 1990's and know full well the shortcomings of these drugs. This was in the early stages of the massive epidemic of obesity in young people that we see today. As a consultant I sometimes work in donut shops where there is free Wi-Fi. It is no coincidence that the vast majority of people I see in the donut line are obese.
There is no mystery to why so many people are obese. Caloric intake greatly exceeds caloric expenditure. Add to this the dropping of Phys-Ed in many schools, hours on end playing video games or watching TV and not getting exercise after school; there are no secrets here.
I used to think that the diet pills were a crutch at best. Now I'm afraid they will regain popularity because 1) people refuse to get off their behinds and work up a sweat these days, and 2) with people's busy lives they are more than ever looking for a magic pill or a quick fix.
I also predict an epidemic of temporomandibular joint disease, what with people trying to open their mouths wide enough to inhale a Triple Baconator Deluxe.
Excuse me. Time to hit the gym
Vet--Did you work on one of the fen-phens?
If so, wonder if you think Wyeth et. al. have been treated faily in the courts, etc.. Real question, not a "set up"!
Vet: With all due respect to (and "for") Justice, some questions are best left unanswered in a public forum.
JiM, I'm not sure if my Confidentiality Agreement is still in force, but I will say that I did not work on Fen-Phen. I did participate once in a roundtable discussion when Orlistat (Xenical) was first introduced, and with respect to gastrointestinal side effects, as Searching 2000 said, perhaps some things are best left out of a public forum
Topiramate is a great drug for weight loss. It's one of the few psych meds I've been prescribed that doesn't cause weight gain. It isn't effective for bipolar disorder and it causes cognitivr difficulties (CRS - can't remember s**t). Adderall for my ADD didn't counteract the negative effects of "Dopamax". I pity those who "ask their dr" about Qnexa!
11 minutes from JiM's post to the chill note from "Searching."
What more do we need to know?
No one would have worked on Phen-Fen. It wasn't a studied or an approved combination. It was that dex-fenfluramine (Redux) was used (and pushed) off-label in combination with phenteramine and that was what exaserbated the problem that occurred with each of them singly but at lower rates. Although as I recall with dex-fenfluramine or fenfluramine alone there is evidence of pulmonary arterial hypertension (PAH) already developing on 2D echo in 30% of patients after 3 months of use.
Salmon
What's fascinating about Arena's lorcaserin is that it's actually got the same biological target as fenfluramine. Arena designed the molecule to be more selective for the target, which they thought might lead to a better safety profile. So far, that seems to be the case.
http://cenblog.org/the-haystack/tag/lorcaserin/
I have to think that people are salivating at the idea of combining phentermine and lorcaserin, if the latter's approved. (New Phen-Fen? Lorca-Phen? anyone?) But the tests on the combo aren't there and aren't likely to happen..
Good point, Salmon.
Beyond that, I appreciated Vet's response, and I certainly respect confidentiality agreements and other good reasons to post with care.
Also, I think it's a tribute to Ed and Pharmalot that the blog is followed closely.
Happy holiday to Canadians, Americans, and anyone else who's celebrating!
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I think that this medication that the FDA may approve called Lorcaserin could be a fairly effective treatment, however as with any drug there are side effects even if low. Regardless more here http://www.lorcaserinpill.com/
I think phen-phen was wonderful. I lost 30 pounds & have kept it off all these years later. It was supposed to be used for 3 months. The people who kept going to different doctors to get more & more ruined it for everyone. If you're overly obese, your heart is going to give out. A few abusers ruined the chances for thousands - & then blamed companies.