I am acutely aware of the obesity epidemic in this country. I’ve posted previously about how obesity may have surpassed smoking as the #1 preventabe cause of death in the U.S. Still the FDA approval today of Belviq, a sertonergic drug that brings back memories of Fen-Phen, Meridia and Redux (dexfenfluoramine) over concerns with their association with valvular heart disease, pulmonary hypertension and other concerns. The studies to date have been necessarily relatively short term, and the FDA is requiring Arena Pharmaceuticals to do continued aftermarket surveillance for these concerns.
My dilemma as a physician is how to balance the potential benefit of moderate weight loss vs. the potential for side effects from Belviq. Belviq appears to have some patients who respond well to treatment, while others respond less well. The anticipated weight loss is more than 5% of body weight over the initial 12 weeks o f therapy, with further weight loss expected in patients who continue therapy. Some patients will not respond with the anticipated 5% or more weight loss in the initial 12 weeks of therapy and in those patients it is recommended that the Belviq be discontinued. Obesity is a well-known risk factor for diabetes, degenerative joint disease, and other cardiovascular problems, so it is far from a benign condition. Belviq is a brand new drug, at least superficially similar to prior drugs that were found to have unexpected serious problems with sustained use, and I would argue that its risks are to some degree TBD (to be determined). The issue in its simplest terms is whether a drug like Belviq which offers a hope for modest weight loss is worth taking when the risks are still ill-defined. The answer is going to depend on the benefits side of the equation as much as on the risks side. Patient with morbid obesity may be willing and even appropriate candidates for taking more risk for a hope of weight loss because the potential benefits are larger. Patients with more moderate obesity, in the BMI >30 range for which Belviq has the FDA indication (BMI >27 with other risk factors) may be less likely to get major health benefits, and so the risk-benefit analysis may swing more towards not using the drug as the risks are likely to be just as high for them as in higher risk patients.
My approach for now is going to be to wait a bit to see how the early after-market reports of efficacy and side effects turn out, and if they seem OK to cautiously consider Belviq in carefully selected patients. An individual’s health risks from obesity are related to much more than their BMI. Do they also have diabetes, hypertension, congestive heart failure or osteoarthritic hips or knees? I expect to have patients requesting Belviq soon. I’ve already had patients asking for the generic components of the still-under-review Qnexa (phenermine plus topiramate). I hope that Belviq turns out to be even more safe and effective than the early studies suggest, but I will not be surprised if Belviq turns out to be less effective than early studies suggest and if some so far unfounded fears of cardiovascular side effect risks are realized.
Addendum: Since the publication of this post, and the subsequent reposting on the KevinMD blog the correctness of the information written in this article has been challenged in comments on that blog. In fairness when challenged by the writers of these comments I asked them to have them reposted here to present a balanced discussion. The crux of the disagreement lies in the specificity of the receptor where Belviq has its function. Belviq appears to be much more specific to the receptors that affect hunger than those in cardiac tissue, which may allow Belviq reduce hunger, lead to weight loss and avoid the cardiac side effects of earlier drugs that less specifically stimulated this receptor. See the comments below for more specific details. In addition I have changed the verbiage of the post to more accurately reflect the expected weight loss from Belviq.
Dr. Pullen –
As one of the drug discovery chemists who worked for years on the 2C project at Arena, trying to synthesize compounds that were highly selective for the 5HT2C receptor over the 2A and 2B receptors (among others), I very much appreciate the fact that you have taken the time to revisit your article in order to correct the implication that lorcaserin (Belviq) is likely to lead to valvulopathy. While it is certainly true that we cannot predict exactly what will happen when millions of patients are exposed to Belviq, it is important to recognize that this is always the case with new drugs.
Arena went to extraordinary lengths during discovery, development, and tremendously expensive clinical trials, to ensure that the possibility of valvulopathy was at an absolute minimum. In the final analysis, the market will determine whether Belviq is successful, but in the meantime, let us not cast unfair aspersions on the drug, but rather speak objectively from a position of knowledge. There is already too much misinformation out there to be waded through.
In the same vein, thank you for modifying your remarks regarding the efficacy of the drug, another topic that has proven a minefield of misinformation. Andy Baron has done an excellent job of highlighting some of the most important nuances of the data, nuances that many writers, professional and otherwise, appear not to understand, and yet nuances that make all the difference in the world in terms of the drug’s ability to help a significant portion of obese and overweight people.
Again, thank you for your corrections, and please note that I am no longer employed by Arena nor do I represent the company in any way.
Kind regards,
Douglas Park (aka Avo)
http://www.nextbio.com/b/search/article.nb?id=18095642
For disclosure for reeader’s in private communication with Mr. Ganjavi he does not represent Arena or Belviq in any formal way, but is a stock holder in Arena. I have no financial or stock ownership relationship with Arena and no disclosures to make. DrP.
Joseph is out of town and asked me to repost this for him:
Joseph Dedvukaj • 7 hours ago
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The first thing you should do when a patient asks is be honest. There are “potential theoretical risks” with crossing the street, driving a car, flying in an airplane, using any medicine, etc. however, you are not true to the clinical trials and selectivity studies done on Belviq. I assume you have the ability to comprehend the science involved, but it does not appear you have actually researched Belviq to advise your patients that over 8000 patients in the Belviq studies showed ZERO evidence of Heart issues. The selectivity studies proved Belviq is 105 times more selective to the 2c receptor controlling appetite than the 2b receptor known to cause heart issues. Stick to the science doctor. Now then tell your patients about the clinical evidence of the dangerous side effects with Qnexa use. In the long term use of Phen/Tpm this can cause brain damage. A strict REMS will be used because doctors like you will abuse prescribing this drug. I’ll bet many doctors will circumvent the REMS program and dangerously prescribe the ingredients you mentioned are currently available because their cheaper and less time consuming to prescribe the ingredients. Qnexa offers nothing new to the physicians arsenal for the reasons you confirm – the ingredients have been around for years. If you care to respond be honest to the science and cite from the evidence the FDA experts studied. There is no REMS requirement for Belviq because the issue you speak of has been proven by selectivity studies to be virtually nonexistent. Joseph Dedvukaj, attorney at law.
Dr. Pullen seems not only to be ignorant of the efficacy and safety data from Arena’s 3 phase III clinical trials, but also to be unclear on the medical benefits of weight loss.
For example:
“Belviq, a sertonergic drug that brings back memories of Fen-Phen, Meridia and Redux (dexfenfluoramine) over concerns with their association with valvular heart disease, pulmonary hypertension and other concerns.”
Dr. Pullen completely ignores the extensive research findings on Belviq’s very specific activation of the 5HT2C receptor. It is outrageous to blindly lump lorcaserin in with fenfluramine and dexfenfluramine, which activated the 2B receptor associated with heart tissue as much as they activated the 2C receptor associated with satiety. Sibutramine (Meridia) broadly blocks the re-uptake of both serotonin and norepinepherine, which is also released by phentermine. Two years of careful Belviq testing on nearly 8,000 test subjects failed to show any CV signal. Valvulopathy findings were in the 2% range, below what is expected in the general population. Fen-Phen caused valvulopathy in 20%-30% of patients and well within two years.
“The studies to date have been necessarily relatively short term, and the FDA is requiring Arena Pharmaceuticals to do continued aftermarket surveillance for these concerns.”
The aftermarket CVOT studies are being conducted to measure relative rates of major cardiovascular events, such as stroke and heart attacks. Such studies have been recommended for all weight loss drugs, even when no CV signal is detected, to test whether the weight reduction correlates with improvements in mortality and morbidity. These studies are long-term because it takes time until people start dying or having strokes, not because there is concern that extended exposures will reveal previously unknown side effects.
“My dilemma as a physician is how to balance the potential benefit of modest weight loss, hoped to be at most 5% of body weight in 12 weeks with the potential for long-term side effects from Belviq.”
Dr. Pullen’s claims of modest weight loss and “at most 5%” are not supported by any data. He seems to have pulled that figure out of thin air based on some foggy recollection of the advice to discontinue use after 12 weeks unless there has been 5% weight loss. In fact those who completed a year on Belviq averaged 8.2% weight loss, and if you count only the “responders” who lost at least 5% then the average was 11%. It is outrageous again that Dr. Pullen can bring in diabetes without even mentioning the stellar effects Belviq had on glycemic measures (.9% reduction in HBA1C, which was .5% greater than placebo, and a 27% reduction in fasting blood sugar). In addition, he ignores the clear medical evidence that even “modest” 5% weight loss can reduce the risk of diabetes by 60% (http://eurheartjsupp.oxfordjou….
“The issue in its simplest terms is whether a drug like Belviq which offers a hope for modest weight loss is worth taking when the risks are at best ill-defined.”
The fact that few risks emerged in the clinical trials does not mean they are ill-defined.
“The answer is going to depend on the benefits side of the equation as much as on the risks side. Patient with morbid obesity may be willing and even appropriate candidates for taking more risk for a hope of weight loss because the potential benefits are larger. Patients with more moderate obesity, in the BMI >30 range for which Belviq has the FDA indication (BMI >27 with other risk factors) may be less likely to get major health benefits, and so the risk-benefit analysis may swing more towards not using the drug as the risks are likely to be just as high for them as in higher risk patients.”
Another outrageous statement, blithely tossed out as if it were medical wisdom when in fact it is completely false. Weight loss of 5%-10% is at least as valuable for obese patients as for overweight patients, even though they may still be obese after the weight loss. This is especially true for diabetes risk.
“My approach for now is going to be to wait a bit to see how the early after-market reports of efficacy and side effects turn out, and if they seem okay, to cautiously consider Belviq in carefully selected patients.”
So, he has more faith in hearing anecdotal evidence based on early aftermarket reports than in large, two-year, double-blind, placebo-controlled clinical trials.
“An individual’s health risks from obesity are related to much more than their BMI. Do they also have diabetes, hypertension, congestive heart failure or osteoarthritic hips or knees?”
Well, that’s exactly why the label calls for such comorbidities being present if BMI is under 30. Those with obesity-level BMI are demonstrably at greater risk for developing these conditions, if they aren’t already present.
“I hope that Belviq turns out to be even more safe and effective than the early studies suggest, but I will not be surprised if Belviq turns out to be less effective than early studies suggest and if some so far unfounded fears of cardiovascular side effect risks are realized.”
It’s hard to imagine how Belviq could turn out to be safer than early studies suggest, unless fewer people end up with transient headaches — the only adverse event that occurred over 5% more in active than placebo arms of the trials. There were no clinical safety signals in the phase III studies, and the efficacy observed was clearly adequate to support widespread use of Belviq.
Reza: Kevin did not write the article, I did. I am open to comments, and appreciate them The article is an opinion, and I’ll stick with what I wrote. I appreciate your comments. DrP.
These numbers might be of use regarding efficacy:
47.5% of patients who took Lorcaserin lost at least 5% of their weight versus 20.3% for placebo patients. Of those completing the studies, 63.9% lost greater than 5% of their weight, 34.7% lost greater than 10% of their weight, and the top 25% lost over 16.7%. The average completer weight loss was 26 pounds or 8.2%. It has been scientifically proven that even a 5% drop in weight can result in meaningful improvements in overall health.
Kevin
You’re hereby requested to immediately deleted retract or correct the false information you posted in your blog piece
http://www.kevinmd.com/blog/2012/07/belviq-patients.html
Read the comment left on your blog by Andy Baron. Your piece is misrepresenting, defamatory, and misleading. I am not going to assume that you’re a “paid shill” as someone has posted that they think you are but I attribute your foolish statements to being uninformed, or maybe trying to be provocative. I hope you’re not being played in the hands of 46 Million short interest and crooks who have been bashing Arena since it was $2 and being consistently wrong on their prediction of AdComm result, PDUFA, and now they’re still bashing the company. So be careful, they are 100′s of millions of dollars in the red and can use any help to get them out of their hole.
Regardless of your motives, you need to correct this post or delete it. As it is it is highly damaging to Arena and its shareholders and it is doing the medical community and 10′s of millions of obese Americans a disfavor by spreading misinformation. Please let me know what you’re planning to do.
Thank you
Reza Ganjavi
Since you seem to be concerned about diabetes in the obese and overweight population you might want to consider this drug because it did show a pretty significant reduction in A1C in the diabetes population even on some patients who did not lose that much weight. I would think for the pre-diabetic population this would be a good drug to consider instead of actual diabetes drugs which may cause weight gain and other more serious side effects. Also keep in mind that there have been two years of additional testing beyond the early studies that you are referencing. The FDA set the bar much higher for obesidy drugs and has been very careful not to approve another Fen-phen or Vioxx.
It is the continued medicalization of behavior. A sad commentary on humanity.