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New Diet Pill Hope 2010-03-01

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Three Articles: Submission: 2010-03-01, Speculation: 2010-07-15 & Result: 2010-07-15

Submission: 2010-03-01

Vivus Inc‘. today announced that ”The US Food and Drug Administration‘ (‘The FDA’) has accepted for filing the company’s new drug application (‘NDA’) for its investigational drug, ‘Qnexa‘, for the treatment of obesity.

The target date for ‘The FDA’ to complete its review of the ‘Qnexa’ ‘NDA’ is 2010-10-28.

In previously announced pivotal phase 3 trials, patients treated with all three doses of ‘Qnexa’ achieved significant weight loss compared to placebo, and significant dose-related improvements in a variety of secondary endpoints including reductions in cardiovascular, inflammatory and metabolic risk factors.

‘”The FDA’s” acceptance of the “Qnexa” “NDA” marks an important milestone in the development of “Qnexa” as a treatment for patients who are obese or overweight with co-morbidities,” stated Mr.Leland F. Wilson, chief executive officer for ‘Vivus’.

‘We believe that “Qnexa” —  if approved — will play an important role in treating the millions of patients living with obesity and related diseases, and who are in need of safe and effective options.’

About the Phase 3 Obesity Program

The phase 3 clinical program, which evaluated “Qnexa” in more than 4 500 patients, was designed under a Special Protocol Assessment with the US FDA and consisted of three trials: EQUATE (OB-301), EQUIP (OB-302) and CONQUER (OB-303).

The EQUATE study was a 28-week randomized, double-blind, placebo-controlled, 7-arm, prospective trial with patients randomized to receive once-a-day treatment with mid- or full-dose ‘Qnexa’, the respective phentermine and topiramate constituents, or placebo.

The average baseline BMI of the study population was 36.3 kg/m2 with an average baseline weight of 223 pounds. The EQUIP and CONQUER studies were 56-week, randomized, double-blind, placebo-controlled, 3-arm, prospective trials with patients randomized to receive once-a-day treatment with low-, mid-, or full-dose ‘Qnexa’, or placebo. In EQUIP, the average baseline BMI of the study population was 42.1 kg/m2 with an average baseline weight of 256 pounds (116 kg); in CONQUER, the average baseline BMI of the study population was 36.6 kg/m2 with an average baseline weight of 227 pounds (103 kg). All patients were asked to follow a hypocalorific diet representing a 500-calorie/day deficit and advised to implement a simple lifestyle modification program.

Speculation: 2010-07-15

Vivus Inc‘, hoping to win approval to sell the first new prescription diet drug in more than a decade, told US American medical advisers today (2010-07-15) that its weight-loss pill gives patients a safe option for shedding kilos and improving their health.

‘Vivus’ is seeking ‘Food and Drug Administration‘ (‘The FDA’) support to sell its drug, ‘Qnexa‘ (Q-NEX-uh), to adults to use once a day to slim down. But first it must prove its pill avoids side effects that have sidelined previous products.

The stakes are huge for ‘Vivus’ and its investors, who have pushed the stock value up more than 130 per cent in the past year, drawn by the potential for huge sales to millions of overweight US Americans.

‘The FDA’ advisory panel will weigh ‘Vivus’s’ data before deciding later on todaywhether to back the drug.

Investors are also watching the panel meeting for clues on the approval potential for two rival drugs from ‘Arena Pharmaceuticals Inc‘ and ‘Orexigen Therapeutics Inc‘, whose shares have also soared.

‘Arena’ shares were up more than 30 percent in early afternoon trading on the ‘Nasdaq’, while ‘Orexigen’ was up 7 percent.

‘The FDA’ staff largely support the effectiveness of ‘Qnexa’ —  the first of three potential new diet drugs up for review this year — but they are concerned about its effect on foetuses, mental health and heart rate. Memory loss and other cognitive problems and body acid changes are also important issues.

That assessment, released earlier this week, was cheered by investors who sent ‘Vivus’ shares up nearly 20 percent, betting the safety issues were not serious enough to keep ‘Qnexa’ from pharmacy shelves. Trading in the shares was halted on this morning ahead of the FDA advisers’ decision.

‘The safety risk associated with “Qnexa” are known … we did not observe any surprises,’ said ‘Vivus’ consultant Mr. Neil Gesundheit, adding most patients saw at least 10 percent weight loss when taking the pill along with a better diet and more exercise.

Those who took the highest dose for a year and did not quit over side effects lost a median of 15 percent of their body weight, or roughly 16 / 18 kg, Mr.Gesundheit told panellists.

These levels of weight loss are unprecedented,’ he said.

If approved, ”Qnexa would offer a potential fat-fighting jump-start to the more than two-thirds of US Americans who are overweight — and would boost a nearly 20-year-old biotech company that has not had a US product approved since 1996.

  • Last year, prescription and over-the-counter diet drugs took in just 381.5 million USD (247.5 million GBP), according to IMS Health.

If ‘Qnexa’ gets the FDA’s green light, that figure could soar. Analysts estimate it could see 689 million USD in sales by 2014, according to consensus forecast data from ‘Thomson Reuters’.

Current weight-loss drugs have not gained much traction, as most only trim a few kilos, but carry serious or unpleasant side effects such as heart risks or flatulence.

‘It’s clear that we need new medical therapies to manage the epidemic of obesity,’ said Mr.Louis Aronne, a Weill-Cornell Medical College professor who spoke on behalf of ‘Vivus’.

Weight can be managed with diet and exercise and surgery is also an option.

‘FOCUS ON SAFETY’

‘In general, “The FDA” is in agreement with the company with respect to the weight-loss effects of the drug,’ said Mr. Eric Coleman, deputy director of ‘The FDA’ division that oversees metabolic drugs.

‘The focus is primarily on safety.’

‘Qnexa’s’ potential to cause congenital defects in unborn babies is a particular concern, especially since women of child bearing age are the pill’s target customer.

So far, analysts have remained confident about ‘Vivus’s’ ability to overcome safety hurdles.

‘The critical factor in looking at the data is the enormous benefit that (Qnexa) provides,’ said Mr.Ira Loss of ‘Washington Analysis Corp’, who follows the FDA for financial clients. ‘The risks are not insurmountable. They can be managed.’

‘Qnexa’ attempts to improve on the infamous ‘fen-phen‘ diet drug. It combines one of fen-phen’s ingredients — the appetite suppressant phentermine — with the anti-seizure drug topiramate. Fen-phen’s other ingredient, fenfluramine, was withdrawn in 1997 when serious heart valve problems emerged.

Patients taking ‘Qnexa’ saw between 3 per cent and 9 per cent weight loss over placebo, depending on how much of the drug they took, ‘FDA’ staff said. Patients also saw improved blood pressure and better fats and sugar levels in the blood.

At least one panellist, University of California Los Angeles medical professor Mr.Sanjay Kaul, said he wanted to make sure the possible risks did not overshadow kilos lost.

Current diet pills include ‘Abbott Laboratories” ‘Meridia‘, which carries several heart-related risks, and ‘Roche Holding AG’s‘ ‘Xenical‘, which causes liver problems and uncontrolled bowel movements.

Imagine what a drug can do that doesn’t have side effects and removes more weight,’ said ‘Leerink Swann‘ analyst Steve Yoo.


Result: 2010-07-15

The Endocrinologic and Metabolic Drugs Advisory Committee of the US Food and Drug Administration (‘The FDA’) has failed to endorse recommendation of the obesity drug phentermine/topiramate (Qnexa; Vivus, Inc) because of concerns about its safety.

The initial tally in today’s committee meeting was 9 against and 7 in favour but this later changed to 10 against, when 1 panel member admitted he had made a mistake due to unfamiliarity with the voting procedure.

All agreed that Qnexa was very effective in inducing weight loss, but even those panel members who voted to give Qnexa the benefit of the doubt struggled over a litany of adverse events seen with treatment, including depression, anxiety, sleep disorders, attention, memory, language and other cognitive disorders, metabolic acidosis, increased heart rate, and teratogenicity.

Despite these serious adverse events, the panel felt that effective drugs are needed to treat obesity. Some of the panel offered ‘The FDA’ suggestions for registry and pharmacodynamic studies, and longer follow-up out to 5 years.

‘Clearly we need more information about this medication, but the type of information we need, particularly with respect to teratogenicity, cannot be gained in a clinical trial setting, it can only be gained once the drug is on the market and large numbers of individuals are exposed to it,’ said Mr.Michael A. Rogawski, MD, PhD, professor and chair of neurology at University of California, Davis, in Sacramento California, in explaining his yes vote.

Ms.Jessica Henderson, PhD, of Western Oregon University, Monmouth, Oregon, and the acting consumer representative on the panel, also voted in favour of approval, although she admitted vacillating between yes and no because of the lack of long-term safety data. What pushed her to vote yes were data that showed that individuals taking ‘Qnexa’ had a significantly improved quality of life compared with those on placebo.

‘As a consumer representative, I put a lot of credence into quality of life and the pursuit of life, liberty, and happiness and a patient’s right to those things,’ she said.

Statistician Mr.Michael A. Proschan, PhD, from ‘The National Institutes of Health, Bethesda, Maryland‘, admitted he had a very difficult time deciding his vote. The short follow-up, just 1 year, was the reason for casting his no vote, he said.

‘A lot of these potential problems are brain related — depression, anxiety, memory, cognitive, and that always makes me worry a little more than with other kinds of problems. I don’t think we have enough data to be able to say whether they are serious issues or not. I think if we had had longer follow-up I probably would have voted the other way but I just don’t feel comfortable with 1-year follow-up,’ Dr. Proschan said.

Acting Chairman, Mr.Kenneth D. Burman, MD, from ‘Washington Hospital Center in Washington, DC‘, said he hoped that his no vote will prompt further discussion with ‘The FDA’ to address the safety issues.

‘We know that obesity is a major health problem and all efforts to address this issue should be lauded,’ he said.

‘”Qnexa” does meet — or exceed — the agency’s requirement for efficacy.

‘On the other hand, the medication has serious potential adverse effects, including potential teratogenicity, increased suicidal ideation, cognitive issues, decreased bicarb, tachycardia, and possible renal stones.

‘Some of these side effects are serious and could be life-threatening — and they have to be weighed against the potential of a relatively modest weight loss and its long-term health benefits.’

As did Dr. Proschan, Dr. Burman said that 1 year was not long enough to allow him to recommend approval with confidence.

‘This medication will be used for a much longer time frame in a much wider population and it is difficult to extrapolate the potential adverse effects to this larger population.’

Safety concerns should be dealt with before a drug is approved –not afterwards, said Ms.Katherine M. Flegal, PhD, from ‘The Centers for Disease Control and Prevention, Hyattsville, Maryland‘. Approving ‘Qnexa’ before addressing them would be ‘a public health experiment and a large gamble,’ she said.

Mr.Abraham Thomas, MD, MPH, Whitehouse chairman of Endocrinology at ‘Henry Ford Hospital, Detroit, Michigan‘, agreed. Formerly medical director of the weight management program at ‘The Brigham and Women’s Hospital in Boston‘, where he cared for thousands of obese patients, Dr. Thomas said that the currently available obesity drugs leave much to be desired, with little effectiveness and lots of adverse effects.

“Qnexa” is far superior to anything that’s on the market,‘ he said.

‘But our concerns are with safety. These have to be addressed, and I think it’s best if these are addressed before approval.’

Dr. Thomas also raised a concern about bone health with ‘Qnexa’ because of the metabolic acidosis that occurs with its use. This could affect peak bone mass in younger individuals, and osteoporosis and fracture risk in older subjects, he suggested.

As did other panel members, Dr. Thomas said obesity drugs need to be considered in terms of long-term use.

‘I think we have to get away from the concept of usage for the short term.

‘Obesity is a chronic disease, I would never go to someone who has high blood pressure and say, “Your blood pressure is normal; now we stop all your medications, see you in a year.” But yet with obesity we view it that way.

‘So we have to look at the long-term safety of these medications so we can prevent weight regain.’

Mr.Lamont G. Weide, MD, PhD, of ‘The University of Missouri, Kansas City, Missouri‘, seconded Dr. Thomas.

‘It doesn’t surprise me that among people who are treating people with obesity that we are starting to call it a chronic disease.

‘When you think that way, you look at the drugs differently, and you have to say, “Tell me what’s going to happen with my patients as I allow them to stay on the medication.”  — that’s one of the things that bothers me.

‘If, with a year’s trial, you have double the depression risk, and you have some cardiovascular questions, I would like to see it extended, so that we can find out whether or not these safety concerns are going to be a major issue.’

Dr. Weide added that he was tired of having to take drugs off the market after they have been in use for a few years because of failing to identify problems.

‘That really is some of what has given “The FDA” a bad reputation outside in the public. We have a responsibility to protect the public at large.

‘As much as I feel for the people who want this drug and want to lose weight, we have to protect the population at large and we need longer-term data with the people who are really going to be using it out there, rather than a select group of patients in fairly good health,’ Dr. Weide said.

One panel member who voted to recommend approval said he feared that the nay-sayers would be sending the wrong message to people who struggle with their weight.

‘I voted yes; I agree that the population at large needs to be protected from dangerous drugs. However, one third of that population is already obese and there’s a very large segment of the population who are headed that way,’ said Mr. Ed J. Hendricks, MD, medical director of ‘The Center for Weight Management, Roseville and Sacramento, California‘.

‘Qnexa fills a gap our treatment spectrum,’ he continued.

‘The sponsor did an outstanding job of managing several very difficult clinical trials.

‘The data show that the drug is reasonably safe in the target population, which are the obese patients. We should approve it. If we say no, we will send a very bad message to our obese patients.

‘This will further drive them away from seeking medical solutions to their weight problem to all the various quackery things that are out there. I hope “The FDA” doesn’t just go by the yes-no votes.’

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