Obesity is not just a morbid lifestyle for millions of American and others world wide, it has become a major health concern. The number of obese adults in 2010 is 35.7% and about 17% of children and adolescents are obese. Obesity is associated with increased risks of coronary heart disease, diabetes mellitus (Type-II), cancer, and other chronic diseases. Health and Human Services Secretary Kathleen Sebelius said, when measured in terms of cost, obesity is already worse than cancer: "About $147 billion a year are spent directly related to obesity and the underlying health conditions related to that. That compares with all the cancers that people have across America, which cost a little under $100 billion a year."
In order for congress to control the costs of health care, they need to place the obesity epidemic at the top of their agenda. The Senate Appropriations Committee "is concerned with the absence of novel medicines to treat obesity, the second leading cause of preventable deaths in the United States and a disease linked to cancer, high blood pressure, heart disease, diabetes, and stroke." The committee directs the FDA to report by March 30, 2012 on the steps it will take to support the development of new treatments for obesity.
There are three drugs currently on the table to combat obesity. I will only talk about Vivus' (NASDAQ:VVUS) Qnexa and Arena's (NASDAQ:ARNA) Lorcaserin since they are up for FDA approval in the next few months. Orexigen's (NASDAQ:OREX) Contrave is a long way away from getting approved.
The first drug is Qnexa which is not a novel drug but a combination of two drugs being used right now. The FDA advisory board had just recommended it for approval by 20-2 in February. It was originally up for FDA approval on April 17, 2012 but was recently delayed for three months. I think the increased heart rate, birth defects, suicidal tendencies and memory loss are worrying the FDA not to mention the five heart attacks during the clinical test and the possibility of heart valve issues. "Public health cannot tolerate another diet drug approved that has not been accepted for cardiovascular risk especially in light of the suggested findings of Qnexa," Sidney Wolfe, director of the health research group at advocacy group Public Citizen, told ABC News. A requirement for obese women of child bearing age taking Qnexa is to be on birth control medication. Women are advised to use and agree to use two forms of birth control during the study. So not only do you have to worry about the side effect of Qnexa, now you have to be concern with the side effect of the birth control pills (BCP). One of the side effects of BCP is weight gain. So you take BCP to gain weight and then Qnexa to lose it back. Other BCP symptoms may indicate a more serious disorder, such as liver disease, gallbladder disease, stroke, blood clots, high blood pressure, or heart disease. At a recent advisory meeting on obesity, Dr. Kaul made a point to mention that drugs with a better efficacy should have a more relaxed threshold for safety. If this is the case, then why pull Meridia or Fen Phen from the market.
The next drug up for approval is a novel drug, Lorcaserin, by Arena Pharmaceutical. Its weigh loss efficacy is a little less than Qnexa but it makes up on the safety issues which can't be said about Qnexa. Below are 3 reasons why I think Lorcaserin will be approved.
Efficacy- Lorcaserin did meet the requirement for approval according to the 2007 FDA guideline.
1. BLOOM trial- results for those who have completed the 52 weeks of study participation
- Lorcaserin participants lost 8.1 kg of initial body weight
- Placebo participants lost 3.3 kg of initial body weight
- During year two, the Lorcaserin group was better able to maintain > 5% weight loss than were those who switched from Lorcaserin to placebo.
2. BLOSSOM trial- results for those who have completed the 52 weeks of study participation
- 63.2% of patients lost at least 5% of their body weight
- 35.1% lost at least 10% of their body weight
- The top 25% lost an average of 16.3% or 35.1 lbs
3. BLOOM-DM trial- Type II diabetics have the most difficult time at losing weight
- 37.5% lost at least 5% of baseline body weight compared to 16.1% for placebo
- 16.3% achieved at least 10% weight loss compared to 4.4% for placebo
Secondary endpoints (Cardio-metabolic Effects)- The reason Congress is pushing the FDA for a novel obesity drug is not for vanity but to reduce the risk of heart disease, cancer, diabetes mellitus, and other chronic diseases which are associated with being obese. Besides weight loss, Lorcaserin treated patients significantly reduced waist circumference, fasting glucose, fasting insulin, HgA1c, systolic and diastolic blood pressure, total cholesterol, LDL-cholesterol, and triglyceride levels. More patients who took Lorcaserin twice daily than placebo decreased total daily use of medications to treat dyslipidemia and hypertension.
The BLOOM-DM study results showed Lorcaserin in Type-2 diabetics, significantly improved glucose control. Lorcaserin decreased HbA1c by almost 1% and decreased fasting glucose by 27% which is in line with other diabetic medication such as Victoza which was surprisingly approved by the FDA with link to cancer in rats. Victoza causes dose-dependent and treatment-duration- dependent thyroid C-cell tumors at clinically relevant exposures in both genders of rats and mice. It is unknown whether Victoza causes thyroid C-cell tumors, including medullary thyroid carcinoma, in humans, as human relevance could not be ruled out by clinical or nonclinical studies.
The FDA approved a drug with a sole purpose of glucose control in Type-II diabetics with cancer in rats at clinical dose which they cannot rule out in human. However, they have an issue with Lorcaserin, a drug which not only help obese people lose weight but improved their overall cardio metabolic health and does the same thing as Victoza for Type-II diabetics and does not cause cancer. I would have to agree with Ron Paul that the FDA is in bed with big pharmaceutical companies if they turn down Lorcaserin. It would be a great injustice for millions of people depending on this drug.
Safety- Lorcaserin is an effective weight loss drug with a great safety profile. Lorcaserin was accepted by the European Medicines Agency for marketing authorization. This is the same agency that rejected Qnexa due to safety issues. Unlike Qnexa which increases heart rate which may lead to valvulopathy, Lorcaserin decreases heart rate and decreases your chance of having valvulopathy as seen in the BLOSSOM study. Patients with preexistent valvulopathy increase in mitral or aortic FDA-defined valvulopathy at week 52:
- Lorcaserin 10 mg twice daily: 12% (preexistent valvulopathy was 5.2%)
- Lorcaserin 10 mg daily: 11.1% (preexistent valvulopathy was 3.9%)
- Placebo: 30.6% (preexistent valvulopathy was 4.1%)
As you can see, Lorcaserin not only does not cause valvulopathy but it is more beneficial for patients with preexistent valvulopathy. In regards to the rat tumor issue, the 5 pathologists approved by the FDA have already cleared that up. The caused of the tumors in these rats are due to the increased levels of rat-specific-prolactin induced by Lorcaserin and not Lorcaserin directly. Many other approved drugs are known to cause this same reaction. One of them is Lipitor, the most commonly prescribed drug for high cholesterol. The only time you see carcinoma in the rat is at the high dose (82X). There is not a single case of tumor in any of the 8,000 plus study subjects. Qnexa, however, has 5 heart attacks out of 5,000 plus study subjects or a 1 in a 1000 chance of getting a heart attack. That is 10,000 heart attacks for every 10 million users. I don't think that is sitting well with the FDA. Imagine these patients taking 82X the dose; Cancer would be the least of their worries.
At the end of the day, I'm pretty sure both drugs will be approved. The FDA delayed Qnexa to give Lorcaserin, the safer of the two, a head start. Lorcaserin already has a manufacturer, Eisai pharmaceutical, ready to mass produce the drug. This will give the patients a chance to try out Lorcaserin for about 6 months since Qnexa will be approved with a REM study attached. This way, the FDA will not feel the heat from Congress by allowing patients to have a choice in which drugs they want to use especially for obese women of child bearing age who do not want to be on birth control medication in order to lose weight.
Disclosure: I am long ARNA.