About two years ago I wrote a blog about the latest two weight loss drugs to be rejected by the FDA. One of these drugs was Qnexa a combination pill made up of two well established medications, phentermine and topiramate (Topamax). At that time the FDA felt there was not
In just the last few months the FDA shot down applications from three new weight loss drugs
and removed one from the market that was previously approved. A month ago, based on
analysis of these actions, I predicted it will take 10 years for a new weight loss drug to be
approved by the FDA. The latest action by the FDA makes me more confident than ever, in this
A sensational action by the FDA to cripple development of new weight loss drugs came
about two weeks ago. The FDA denied approval to the weight loss drug candidate Contrave,
a combination of two medications. Both of the drugs in the combination pill are presently in
use and were FDA approved decades ago for indications other then weight loss. One of the
drugs Naltrexone, is used to treat opiate drug overdoses and the other bupropion HCL is used
to treat depression. Given the long history of safety of both drugs it would seem surprising
the FDA would reject the combination of these drugs on grounds of safety concerns, which
was what happened. Making the FDA rejection even more astounding is that just a month
before, a majority of members of the FDA’s own Endocrinologic and Metabolic Drugs Advisory
Committee, gave a thumbs-up to Contrave. In almost all previous instances where the Advisory
Committee gives their green light to a new drug candidate, the FDA has followed through with
an approval. I can hardly imagine a clearer way for the FDA to say “Drop Dead!!” to all those
seeking to get approval for a new weight loss medication.
Michael Narachi, CEO of Orexigen the maker of Contrave, is quoted as saying he “was
surprised and extremely disappointed with the agency’s (FDA’s) request”, a request which
essentially ended any chance of getting approval for his company’s weight loss drug. My advice
Michael, is to move on with your company and find another drug class to work on. Maybe
something to smooth away skin wrinkles or relieve constipation. I’m sure you will have a lot
more success. In the meanwhile, the epidemic of diabetes type 2, cardiovascular disease, and
disabilities due to degenerative joint disease, all related to obesity, marches on.
A final note of advice to investors in the medical field. I would spend my money on a psychiatrist
before investing money in companies conducting research on weight loss medication, since you
won’t see a penny from your investment for ten plus years.
Gary Pepper, M.D.
As a culture we don’t plan for a sudden halt in scientific advancements. Our tendency is to expect progress to be rapid and continuous. My prediction is that in certain areas of medical science we are likely to see not only a halt in progress but a slipping backward. In particular, the realm of medical weight management is in complete disarray at this time. Two new drugs designed to induce weight loss have been shot down by the FDA in the last few months. The first is Qnexa, developed by Vivus Inc. Interestingly, Qnexa combines two drugs already approved for use in the U.S. One of the drugs is phentermine which is a medication used for decades as an appetite suppressant. The other is a common drug used to treat seizures with the brand name Topamax (topiramate) which also induces weight loss. The drug performed admirably in clinical trials with most participants losing over 10% of body mass. The FDA cited excessive risks of the drug in its statement of rejection. One wonders why the drugs are still being marketed separately if they are so dangerous.
The latest drug to be rejected by the FDA is Lorgess (lorcaserin), developed by Arena Pharmaceuticals. This drug, not as effective as Qnexa, produced 5% body mass loss in about half of participants in clinical trials. Lab animals showed a tendency to develop breast tumors when exposed to the medication, adding to the FDA’s decision to reject the drug application based on safety concerns.
I am a strong advocate of drug safety and regulation. On the other hand we know obesity, and with it Type 2 diabetes, is epidemic in the U.S. I regard weight loss as the “holy grail” when treating type 2 diabetes and yet it is the most difficult goal to achieve. Any drug which could assist in weight loss is highly desirable in the treatment of Type 2 diabetes. Not only does blood sugar improve with weight loss but also blood pressure and cholesterol readings show declines. All three of these parameters are known to be prime contributors to the main cause of death in diabetics, cardiovascular disease.
It has already been 10 years since the last drug was approved specifically for a weight loss indication. The failure of these two latest medications to achieve approval is certain to cause the pharmaceutical industry to severely curtail if not abandon further investment in this type of drug development.
Why is the FDA so reluctant to approve a weight loss pill? This is a complex issue but requires an answer. A new weight loss inducing medication is certain to be highly anticipated and widely prescribed. Therefore, from the very first day of approval the FDA must take responsibility for the well being of millions of people who are likely to take the medication. We are a society which demands our medications deliver miraculous cures with no side-effects. If someone perceives they have been injured by a medication our legal system is primed to unleash brutal retribution on everyone remotely involved in the approval process. Abuse and injury with a medication designed to cause weight loss is almost a certainty. This is a no-win situation for the administration of the FDA.
I predict it will be at least another 10 years before a medication for weight loss is approved by the FDA. Unless there is a change in the climate of litigation in this country it will take longer than that. In the meantime the only new developments in weight loss drugs will be the result of exploiting appetite suppressant effects which are the “side-effect” of medications approved for other purposes.
Gary Pepper, M.D.
Phentermine (Adipex) is used as an adjunct to exercise, behavioral modification, and caloric restriction in the short-term management (a few weeks) of obesity. Phentermine therapy is indicated for patients with no underlying risk factor but a pretreatment body mass index (BMI) of 30 or greater and those with an underlying risk factor (e.g., hypertension, diabetes mellitus, hyperlipidemia) and a pretreatment BMI of 27 or greater. Body mass index is an index of a person’s weight in relation to their height.
Phentermine should not be used in combination with selective serotonin-reuptake inhibitor antidepressants (e.g., fluoxetine, fluvoxamine, paroxetine, sertraline) or monoamine oxidase (MAO) inhibitors. To help bring about and maintain loss of weight, the patient must be taught to curtail overeating and to consume a suitable diet. Phentermine also has been used for longer periods combined with fenfluramine (no longer commercially available in the US) in selected patients for the management of this condition. Such combined long-term therapy had been used widely in the 1990s in the management of obesity. However, because of accumulated data on adverse effects associated with the drugs, fenfluramine hydrochloride and its dextrorotatory isomer dexfenfluramine hydrochloride were withdrawn from the US market in 1997.
The usual adult dosage of phentermine hydrochloride is 8 mg 3 times daily, given 30 minutes before meals. Alternatively, 15 or 30 mg of phentermine as the resin complex, or 15—37.5 mg of phentermine hydrochloride, may be given as a single daily dose in the morning.
SIDE EFFECTS: Blurred vision, dizziness, dry mouth, sleeplessness, irritability, stomach upset or constipation may occur the first few days as your body adjusts to the medication. If these effects persist or become bothersome, inform your doctor. Notify your doctor if you experience chest pain, nervousness, pounding heart, difficulty urinating, mood changes, breathing difficulties or swelling while taking this medication. If this medication makes you dizzy or lightheaded, avoid driving or engaging in activities requiring alertness. If you notice other effects not listed above, contact your doctor or pharmacist.
PRECAUTIONS: Tell your doctor your complete medical history especially if you have high blood pressure, an overactive thyroid, glaucoma, diabetes or emotional problems. This medication can be habit forming and must be used with caution. Alcohol can increase unwanted side effects of dizziness. Limit alcohol use. This drug is not recommended for use in children. Consult your doctor or pharmacist for further information. This medication should be used only when clearly needed during pregnancy. Discuss the risk and benefits with your doctor. This drug may be excreted into breast milk. You may have to stop nursing or stop using this drug. Consult your doctor before breast-feeding.
DRUG INTERACTIONS: Inform your doctor about all the medicines you use, (prescription and non prescription) especially if you take high blood pressure medicine or MAO inhibitors (e.g., furazolidone, linezolid, phenelzine, selegiline, tranylcypromine), or any other weight loss medicine. Avoid “stimulant” drugs that may increase your heart rate such as decongestants or caffeine. Decongestants are commonly found in over-the-counter cough-and-cold medicines. Do not start or stop any medicine without doctor or pharmacist approval.
I personally feel that appetite suppressants are not a substitute for a proper diet. Exhaust all nutritional avenues prior to trying any medication for obesity. However, if you are planning on using this medication, for maximum effects, this must be used in conjunction with a personalized diet and exercise program.
Robert L. Pastore, Ph.D., CNC, CN
Senior Nutritionist at Metabolism.com