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Live Blogging the Vivus Qnexa -- FDA Advisory Committee Meeting

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Check back here throughout the morning for updates.

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Morning Minyans. I'm Lisa LaMotta, the biotech staff writer here at Minyanville. Today I will be live blogging the Meeting of the Endocrinologic and Metabolic Drugs Advisory Committee Meeting that will be reviewing the New Drug Application of Vivus' (VVUS) Qnexa.

Please refresh the screen often for updates.

For background on the advisory committee meeting, see FDA Upbeat About Qnexa Ahead of Panel. You can also check out the briefing documents from the FDA here.


8:07 Eric Coleman, M.D. is getting started. Giving background on Qnexa -- a combination of phentermine (previously approved) and topiramate (approved in 1996). FDA agrees that Qnexa is efficacious, but the meeting today will look at five safety issues -- affect on pregnant women, the chance of cardiovascular risks, psychiatric events, cognitive events, and metabolic acidosis.

8:10 Vivus presentation has started. First-up is Dr. Louis Aronne, Weill-Cornell Medical Center talking about unmet medical need for Qnexa. Recommended for obese and overweight patients with a BMI of 27 or greater.

Please send any questions to lamotta@minyanville.com or to @BioWriterChik on Twitter

8:17 Aronne: Obesity affects 1 in 3 American adults. Related to cancer, diabetes, and kidney disease.

8:20 Aronne: 70% of diabetes cases caused by increased weight. "It's easy to see how obesity adds to healthcare costs."

8:21 The initial goal of weight loss therapy is to reduce body weight by approximately 10% from baseline. Health agencies recommend diet and exercise, but inherent biologic responses to prevent starvation make that easier said than done.

8:23 Aronne: Need more treatments for obesity that are covered by insurance.

8:25 Wesley Day, VP of clinical development at Vivus now speaking.

8:26 Day discussing Qnexa clinical trials - including trials int he morbidly obese, and those with other health complications.

8:27 At the end of study 201 patients had lost an average of 25 lbs. Vivus learned that low doses of the two previously approved drugs was well-tolerated by patients and contributed to significant weightloss.

8:29 At the end of study 202, patients had a lower-use of anti-diabetic meds.

8:30 Study 204 on obese patients with severe sleep apnea was not included in the NDA. Vivus is currently researching Qnexa for the treatment of sleep apnea as well as obesity.

8:31 Day begins speaking about phase 3 studies. Including two one-year studies. EQUIP compared high/low dose of Qnexa to placebo. Background program included the LEARN program that included lifestyle modification.

Please send any questions or comments to lamotta@minyanville.com or to @BioWriterChik on Twitter

8:35 Ph3 study included 60% diabetic pop., 57% with hypertension, and almost 30% of patients had a psychiatric history.

8:36 Day: 45% of subjects lost at lest 5% of their body weight. Qnexa met both FDA qualification for weightloss guidelines.

Requirements by FDA for Weightloss drugs:

1) The difference in mean weight loss between the active-product and placebo-treated groups is at least 5 percent and the difference is statistically significant

or

2) The proportion of subjects who lose greater than or equal to 5 percent of baseline body weight in the active-product group is at least 35 percent, is approximately double the proportion in the placebo-treated group, and the difference between groups is statistically significant

8:39 All three doses of Qnexa saw significant weightloss. Day says top dose Qnexa gives greater weightloss benefit to people who have a BMI of over 40.

Please refresh the screen often for updates.

Minyan Da Augi says: I don't think our insurance companies should promote these dietary drugs, BUT SHOULD PROMOTE HEALTHY LIVING (Diet and exercise 1st..w/PROOF) and if that is not working, and doctors can confirm such activities, to then act and provide these drugs NOT PAID FOR (FULL PRICE) and monitor through diet and exercise. We can't just hand these pills out like candy (and every other RX out there). Put the honess back on the patient!!!! WE as people are so Freaking lazy, WE NEED TO HELD ACCOUNTABLE!!!!

8:43 Day: Significant affects from Qnexa on triglycerides and HDL Cholesterol

8:44 Day says Qnexa improves blood pressure and lowers use of blood pressure medications -- LaMotta: This is very important because it shows that Qnexa improves overall health

8:46 Vivus examined the progression to type 2 diabetes on all non-diabetic patients. Qnexa reduced this.

8:47 Vivus assessed Quality of Life in patients including measures of physical function, general health, social functioning

8:48 Day summing up Qnexa efficacy. "We see dose-related affects on weight, as well as dose-related affects on waist. We saw significant improvement on glycemic endpoints."

8:50 Dr. Neil Gesundheit, Stanford Univeristy talking about the common side effects of Qnexa, and the adverse events. Next presenter will discuss the affects on pregnancy.

8:51 Gesundheit: rates of completion in mid and top dose of Qnexa was higher than those on placebo. 72% to 75% of patients on top dose of Qnexa finished the clinical trials

8:54 Gesundheit discussing the increase in heart rate in Qnexa patients accompanied by a decrease in blood pressure.

8:57 Vivus took a closer look at patients who had an increased heart rate -- checking blood pressure levels. Patients on the top dose of Qnexa had a lower systolic blood pressure, while placebo patients had no change.

9:00 One cardiovascular death -- patient on placebo. Total of 17 adverse cardiac events. 9 of those pateitns on placebo. Relative risk of 0.6 of adverse events in Qnexa patients compared to placebo. Important to keep in mind that there were more patients in the Qnexa arm of the study.

9:03 40 adverse events of cardiovascular/neruovascular nature, 22 of those were patients on placebo and 18 on Qnexa

9:05 Two adverse events of metabolic acidosis - an increase of acidity in the bodily fluids -- one of these occured in the mid dose of Qnexa, the other in the high dose group

Seems that data presented by Gesundheit on cardiovascular risk favors Qnexa over placebo. This will become imnportant later when the FDA panelists begin their discussion. You can find a list of those experts here.

9:09 Gesundheit finished speaking. Dr. Kishore Gadde, director of obesity clinical trials at Duke University medical, begins speaking. He has no position in Vivus, but does hold substantial stock in competitor Orexigen Therapeutics (OREX)

Minyan Tim Miles says: The Fed has one or two choices. Ban food that is deemed harmful, or invest in drugs that can counteract the effects of said food. We don't all work 9 to 5 with our spouse cooking wholesome food at home while we bring home the bacon.

9:12 28% of patients had a history of psychiatric events, 21% had depression, and 15% were on depression drugs. Patients were asked a psychiatric survey called PHQ9 at every patient visit to measure the psychiatric effects

9:16 Gadde: "Another way of looking at the psychiatric events was to look at the number of patients who had to get a new prescription for depression medications." The rates were the same for Qnexa and placebo group. No adverse eventsin this category, but three cases of suicidal ideation with no intent.

9:18 Gadde says no increase in suicidality -- this was a concern because of increases in suiciality in topiramate patients at a much higher dosage level of the drug

9:19 Gadde talking about neuropsychiatric events. Says no dose-related neuropsychiatric events. 90% of neuropsychiatric were mild to moderate. Gadde finished.

9:20 Dr. Gideon Koren, University of Toronto, begins speaking. He will focus on the risks to pregnant women. No conflict of interest with Koren.

Please refresh the screen often for updates. Please send any questions to lamotta@minyanville.com or to @BioWriterChik on Twitter

9:23 Koren talking about whether its safe for women to take topiramate during pregnancy. Koren says sometimes it may be necessary due to epilepsy. The drug has been on the market for 15 years and affects are well-known.

Carmen Drahl of The Haystack asks: any talk regarding synergy between the two components and how that might affect AE profile of the combo vs. each drug on its own?

LaMotta: Most of the discussion has been about Qnexa as a whole, but many of the safety concerns stem from the individual components. Koren is now discussing the affects of Topiramate on pregnancy. Presumably he will address the phentermine component next. (Koren did not address affects of phentermine on pregnancy.)

9:29 5 million women receive topiramate -- birth defects are expected. Yet, dosage of topiramate in Qnexa are much lower than those given to women with epilepsy.

9:31 13 women on Qnexa had a live birth. None of those children had birth defects. There was a total of 19 pregnancies during the program despite Vivus asking women to use two types of birth control.

9:32 Koren emphasizes the risks of pregnancy during obesity, which often causes birth defects, still births, and other problems. (this is without any drug interference)

9:33 Koren says that the topiramate component does not increase the risk of malformation in babies. He says that the company should continue to collect data on this to detect signals of problems. He believes that Vivus should have a "very proactive" program to advise women and prevent them from getting pregnant while on this drug.

9:35 Gadde finished. Vivus summarizing adverse events. Vivus believes label should include notes on suicidality and that doctors should be instructed to monitor patients mood. Qnexa created more psychiatric events than placebo.

9:36 patients should use caution when driving a car or operating heavy machinery until they know how Qnexa affects them.

9:38 Topiramate dosage for epilepsy is 400mg -- Qnexa contains 1/4 of that.

9:39 Qnexa should not be used by women who are pregnant or expect to be pregnant. Vivus will continue to monitor pregnancies and will create a register of pregnant patients.

9:40 Qnexa is just one piece of a larger effort that includes diet and exercise. Vivus will engage in an outcomes trial that will measure MI and stroke. "We did not observe any surprises during the clinical trial program."

9:43 Qnexa can help alleviate the need for surgery.

9:43 Vivus is wrapping up its presentation. Questions from panel begin.

Then a quick break and the panel will return with comments from Dr. Mary Roberts from the FDA.

9:47 Questions about dosing fromt he panel. Qnexa contains 15mg of phentermine and 100 mg of topiramate. Assessment of literature is what established the ceiling for the dosage.

9:48 panel asking about weight regain after patients stop taking the drug. Vivus studied this in ph 3. In group of subjects who stopped the drug , but stayed int he study lost 10.9% of body weight and regained about 4% of that.

9:49 Panel now asking about any complications that occurred in patients that took the common diabetes drug metformin as well as Qnexa. About 450 subjects on both drugs. Affects were virtually the same. "No additive affect or interaction with metformin."

9:54 Panelists asking about syncope events - temporary loss of consciousness. Vivus said more patients on Qnexa reported this, but the rates were low.

9:57 Now discussing heart rate again. Panelists ask why Vivus only looked at heart rate outliers for this. Vivus says it wanted to look at people with greater risk.

9:58 Patients int he study were on a diet that reduced caloric intake by 500 calories a day.

9:59 Questions about patients using depression meds -- especially SSRIs. What amount of patients used these?

10:00 Gadde says most cognitive adverse events were happening in the first three months. Increase in the number of drop outs in treatment that later plateaued.

Minyan William Gilbreath notes: Thanks for blogging Vivus-FDA. The point needs to made that the obese to get their Qnexa will be under a doctors care, so there is the benefit of advice and nagging. The placebo alone has some benefit because of this factor, which is additive to the Qnexa action.

10:05 panel asks how frequently heart rate and blood pressure were measured. Vivus says that these were measured at every visit.

Vivus seems totally capable of answering all panel questions in full. The company continues to go back to slides to illustrate its points.

10:07 Panel asking if Vivus did a formal analysis between blood pressure and heart rate. Now looking at sleep-apnea slide. Wondering if it a weight-related result.

10:08 Vivus says that it is driven primarily by weight.

10:09 Panel asks if you get the "same bang for your buck with the low dose and the high dose." Vivus wants all three doses approved because it would allow individualization of therapy.

10:11 Questions about contraception Wondering why the pregnancies occurred despite oral contraceptives.

10:12 Vivus did not confirm compliance with a biochemical measure so they cannot address whether the contraception failed or if patients failed to comply.

10:13 Fifteen minute break. Resumes at 10:30. Time for more coffee!!

10:30 The FDA is back with Dr. Mary Roberts from FDA -- she is currently addressing the efficacy of Qnexa.

Please refresh the screen often for updates. Please send any questions to lamotta@minyanville.com or to @BioWriterChik on Twitter

10:35 Roberts acknowledges that Qnexa satisfies both FDA requirements for efficacy of weightloss drugs -- the FDA only requires a drug meets ONE of these. Although lowest dose of Qnexa did not meet both of these requirements like the two higher doses did.

10:39 Roughly 1000 people were exposed to Qnexa for one or more. About to discuss safety concerns. Efficacy is all goooood!!

10:41 Roberts discussing historical case studies of phentermine and topiramate with regards to psychiatric events. Those doses tended to be much higher than is included in Qnexa. A total of 6700 people were screened to be included in the clinical trials, but many were disqualified due to depression problems.

10:43 PHQ-9 form was administered at every patient visit. This measures feelings about depression, including questions about "whether you would be better off dead." 74.4% of patients at baseline has no depression by PHQ-9

Minyan Willie McCovey asks: Can you get a sense of the mood of the panel on this drug?

LaMotta: Hard to tell so far. Only a few questions have been asked by the panel, but most were asking a clarification of the adverse event data. There were no surprises here and Vivus was able to answer all of the questions clearly. The FDA clearly thinks the drug is effective, but safety is the big question. My opinion is that so far things have been pretty positive.

10:48 Qnexa arm showed greater risk of psychiatric events than placebo, regardless of psychiatric history.

10:50 FDA says no incidence of suicide in Qnexa patients.

Minyan Barry Dreayer asks: One of the commentators of CNBC highlighted that during today's session one of the panelists seemed to be hung up on the birth defect issue. What is your opinion of the impact of the panelist's concern?

LaMotta: There was a focus on the affects of the drug on pregnant women, but I think the panel was more concerned with how these women ended up getting pregnant (despite two forms of birth control) than birth defects. No babies born to patients on Qnexa had birth defects -- although this was a very small number. Dr. Koren did a great job addressing the expectation of birth defects of patients on topiramate (one of the components that makes up Qnexa.)

11:00 Roberts now speaking about metabolic acidosis. There were imbalances noted in bicarbonate levels compared to placebo. But the long-term effects for Qnexa patients with metabolic acidosis on bone health and growth are unknown.

11:05 Pregnancy now being discussed. Of 70 topiramate monotherapy exposed pregnancies - 3 resulted in malformations. Lack of control group means that relative risk could not be established.

Getting lots of questions about why $VVUS is halted. This is not unusual. The Nasdaq usually halts trading on stocks before a high volume trading events. Vivus will likely begin trading again once the meeting has ended.

11:12 Now discussing Qnexa interactions with oral contraceptive. Qnexa did reduce the hormone effect, but it is unclear what the threshold is for becoming pregnant. Also noted that fertility becomes more likely with weight loss.

11:14 Roberts acknowledges that Qnexa animal studies showed increased likelihood of face abnormalities in infants. This is the only really negative comment I've heard so far. Roberts now reading the questions to the panel. You can view those questions here.

11:19 Roberts summed it all up. Now panelists are asking questions. The first question concerns the pregnancy issues.

11:23 Panels asks how a REMS strategy would be applied to the pregnancy issues for category X drugs. A category X warning on Qnexa would greatly limit the patient population since most women who would potentially take the drug would be of child-bearing age.

11:25 FDA says that there is no standard for category X drugs. It varies from drug to drug.

11:26 No one discussed the affects of phentermine on pregnancy. This is a stimulant and panel worries that it might decrease the blood flow to the baby. This has been a huge sticking point for the panel. I expect that they will severely restrict the use of Qnexa to women of child-bearing age. This could be a huge plus to competitors.

11:35 Discussion on blood pressure are ongoing. Panelists seem tobe rehashing those things that were disucssed earlier today.

11:50 Discussing elevation in heart rate by phentermine. Also discussing cardiovascular risks. FDA says its important to find out what the pharmacotherapy benefits of Qnexa would be.

11:53 FDA says blood pressure is not as much of a concern as it is with phentermine alone. Lunch break in five minutes.

11:56 Discussing gender diffrences with Qnexa. Femakes had a slightly higher response rate, but not significant.

12:00 Breaking for lunch. Be back at 1pm with more fun highlights from the Vivus Qnexa panel.

1:00 Panel is back. FDA talking about how it believes in transparency before the open public hearing begins

1:02 Lynn MacAfee, director of medical advocacy at the Council on Size and Weight Discrimination, talking about how lifestyle is important for use in conjunction with diet drugs. She notes that she is an obese woman and that she has taken many diet drugs. She is disappointed that only one-year trials are done. She says that she wouldn't take Qnexa because of the side effects. Adds that cost is a huge problem.

1:05 MacAfee asks if the risk benefit profile is good enough. Now she is bringing up the Fen-Phen issue.

Keep in mind that Phentermine is not the part of the Fen-Phen combination that caused the health problems with the Wyeth drug.

1:10 Patient from the Qnexa study talking about her success on the drug after two years. Her cholesterol and blood pressure have gone down to normal levels. Says she still struggles to keep her weight down, but will definitely take Qnexa if approved. "I will be thin. I will have made it. I will be on my way to a healthy life."

1:12 Kelly Close: editor of three publications about diabetes. She says obesity is a disease. And is reading please from her readers about having a better solution to losing weight.

1:15 Close: One hundred million Americans need more attention! She also notes that obese patients have many other health problems including depression, and nerve damage.

1:17 Close: Diabetes patients surveyed only spent 21 minutes with doctors per visit. She adds that this number is high. "Many doctors have given up. We need more and better options. The drugs don't need to be perfect, but they do need to be available."

1:20 A doctor representing the obesity society is talking about the problems related to the disease, including rapid regaining of weight after a weight loss regimen is stopped. She calls for weightloss drugs to be tested in sub groups that include men and women, as well as patients of different ethnicities -- especially those that that have a high instance of obesity.

1:23 New patient talking about her experience with phentermine. Says it made her so talkative that "even I wanted me to shut up." She says that she has tried everything. She says laziness is not the reason for her weight. She was in the Army for 20 years and now works on a horse farm. Says that she obviously eats more than her body needs and that metabolism is likely an issue.

1:27 Same patient says that she went from a size 20 to a size 10 on Qnexa. Says it helped her change her eating habits -- turned off her brain's hunger signals. She says that she had no negative side effects and that Qnexa lowered her blood pressure. "I believe that Qnexa is a tool that will give people a healthier life both physically and mentally."

1:29 Next Patient: lost 50 lbs during her time on Qnexa. "I experienced no negative side effects." During her time on Qnexa she had a very stressful life including law school and a break-up.

Many of these patients are talking about how ashamed they feel because of their weight. None of them are faulting anyone but themselves. One patient referred to Qnexa as "instant willpower." Listening to these women is heart-breaking. They are pleading for the FDA to help them.

1:33 Member of the Obesity Action Association speaking. "one of the most challenging aspects of being overweight is living with the bias. Too many people believe that obesity is a personal failing. Please evaluate the treatment as you do any other serious medical treatment."

1:37 Public Citizen's Sidney Wolfe chastizing Vivus for only doing one-year trials.

1:38 Wolfe's testimony is the first that has been largely negative -- he doesn't believe the side effects are worth the risk. He thinks its unsuitable for the treatment of diabetes.

1:40 Public Hearing portion is now closed.

1:41 Back to panel questions for the FDA and Vivus

1:42 First questions is regarding the diet and exercise program used with Qnexa. Vivus says that the program used throughout the trial is called LEARN -- patients given food diaries and asked to reduce calories by 500 per day - focused on caloric intake, exercise, and nutrition, reduce portion size and reduced dietary fat as percent of total calories - Vivus gave out pedometers to help establish goals and increase activity

1:45 Placebo subjects had a weight loss of 1% to 2% -- placebo weight loss was slightly higher in the sleep apnea study,but Vivus is not sure why

1:46 Did patients comply with the weightloss program beyond just taking Qnexa? Vivus didn't really have many tools to measure compliance

1:48 Discussing use of beta-blockers by patients in the trial.

1:52 Panel taking issue with the lack of REMS currently being presented, despite Vivus' promises to do extensive surveys and monitoring. Panel wants more specifics on risk management now.

1:55 Vivus said a lot of the semantics are still being worked out. Including Physician education programs.

Please refresh the screen often for updates. Please send any questions to lamotta@minyanville.com or to @BioWriterChik on Twitter. Thank you for reading and for all of your comments, tweets, and emails!

1:57 Panel now asking about the reversibility of depression. Vivus says that high dose Qnexa patients experienced adverse depression events in first three months. Patients with depression reverted back to baseline after they stopped the use of Qnexa.

2:02 Panel now asking about the addictive nature of phentermine. Vivus didn't see any apparent psychiatric withdrawal symptoms.

Atmosphere in the room is pretty quiet. The public commenters were very passionate - made this reporter teary. But the dialogue between Vivus and the panelist right now is pretty calm. I think the panelists seem fairly positive, except when it comes to the pregnancy issue.

Minyan Daniel Walsh asks: it sounds like they may want longer testing. what do you think???

LaMotta: I still believe the panel will vote in favor of Qnexa's approval, but I think Vivus will have a lot of work to do post-marketing. The Qnexa patient population will likely be limited because of the pregnancy issue. Obviously pregnant women will not be prescribed Qnexa, but its doubtful that the FDA will allow all women of child-bearing age to obtain a prescription.

2:12 Panel has once again brought up efficacy in males. Vivus says that 30% of study participants were male.

Minyan Jonathn Vasata asks: I wonder how much the weight loss increased sexual activity... Do you know if that was addressed?

LaMotta: I don't think Vivus has investigated the impact on sexual activity in Qnexa patients. But its likely that it would have been mentioned if there was a negative impact.

Getting lots of questions about the timing of the panel vote -- I think there is a good likelihood that the panel will vote before the market close today. Although that depends on how many more questions are asked. Panelists and presenters have been good so far about not being too long-winded.

Minyan Tim DeJoris makes a good point: "Pregnancy may be a snagging point but that can be avoided with a warning label. We have all seen women that are pregnant or have a chance of getting pregnant warning labels."

Panel will vote on all six questions regarding Qnexa by the end of the day. This will include the question that asks the panel if they believe the benefit of Qnexa outweighs the risks. Panelists will also discuss what sort of labeling or additional studies they recommend.

2:26 Panel now discussing cardiovascular risk again. Vivus brings in the big guns -- a cardiologist is now addressing the panel. Discussing a three to five year trial to assess further cardiovascular risks post-marketing.

2:30 Typical participant in the study was an overweight woman in her 40s. Panel asking if age specificity will be addressed. Answer: drug will be available to those 18 years and older.

2:32 Panel asking the FDA if they can give a clearer statement on the programs currently available for drugs on the market in regards to pregnancy.

2:33 FDA: Pregnancies do occur. We don't have the research to show compliance with birth control. We don't know what contraceptives work. Women learn to give the answers they think will get them the drug.

2:35 Vivus says it's fair to assume that Qnexa would be a chronic therapy.

Minyan Cathy Gordon asks: is this the same panel that ruled on Avandia yesterday?

LaMotta: It is not the same panel that ruled on GlaxoSmithKline's Avandia, but some of the panel members are on both panels.

2:39 Panelist says, "It's clear that this will be a lifelong therapy. People in the audience want this back. I want to hear more on that."

Getting questions about Qnexa and birth control. There were 34 pregnancies during the trials of Qnexa -- 19 of those were patients on the drug. 13 of those 19 babies were born. None of them had birth defects. All women were asked to use two forms of birth control. It is not clear whether they complied with that. A link has not been established between Qnexa and the pregnancies. It is unknown how the drug change the effectiveness of oral birth control. The FDA seems to have little information on this sort of thing as well.

2:46 Panelists decided to eliminate the break. They clearly have no idea how much coffee I have been drinking. Panelists will begin discussing and voting on the questions.

First Question given to panelists: Taking into account the results of the assessments made with the PHQ-9 and the Columbia Suicidality Severity Rating Scale (C-SSRS), please comment on the significance of the increased adverse event reports of depression, anxiety, and sleep disorders in subjects treated with Phentermine/Topiramate (PHEN/TPM).

> If approved, please discuss need for monitoring, possible monitoring strategies, and contraindications for use.

2:51 Panel commends Vivus for including patients with depression

2:51 Panelist says "I do not see [depression events] as a reason not to approve the drug"

2:52 Panels sees doubling of depression risk for high doses of Qnexa, but low-to-no risk of suicide

Panel seems to view this data on depression and mental health very favorably. Another panelist commented that she doesn't see this as a block to approval, but does believe further monitoring is necessary. Another panelist is alarmed that the Qnexa patients weren't overwhelmingly happy once losing weight.

FDA: Quality of life benefits seem to be positive, but its surprising that they are not more positive. Qnexa does not seem to increase suicide, but could potentially increase suicidal ideation. Panel overall seems to think that further studies could be done post-marketing. Possible interactions with depression medications will have to be looked at.

3:00 Time for Question Two:
Please comment on the potential significance of the increased adverse event reports of disorders of attention, memory, language, and other cognitive disorders in subjects treated with PHEN/TPM.

If approved, please discuss need for monitoring and possible monitoring strategies.

FDA: Seems affects on cognition are mild and temporary.

3:02 Panelist says that Qnexa should include warning for people with jobs like pilots or electricians who might be affected by a temporary lapse in cognition.

3:03 Panelist says "We have to pay careful attention to what dose has the most beneficial profile."

Vivus is applying for approval of all three doses.

FDA: Cognitive issues are subtle and seem to be reversible when medication is stopped, but affects of these issues in the larger population are unknown.

3:06 Time for Question Three:
Please comment on the potential clinical significance of the metabolic acidosis determined by decreases in serum bicarbonate levels with PHEN/TPM treatment.

> If approved, please discuss need for monitoring, possible monitoring strategies, and contraindications for use.

3:08 Panel says numbers for metabolic acidosis are small and patients seem to recover quickly. One panelist says that he is not concerned about the bicarbonate issue. Another panelist suggests occassional monitoring of bicarbonate levels.

3:10 First mention of potential use in pediatric population. Vivus has no data on this. Unlikely it will be used for this until much later after many studies.

At this rate, a vote on approval will likely take place around 4pm. Panel seems to be spending about 15 minutes per questions.

3:13 Panelists say that metformin guidelines should likely be used for cut off on treatment in regards to acidosis.

FDA: Metabolic acidosis is a known effect of topiramate. Does not seem to be an issue with Qnexa. Although kidney stones should be monitored. Doctors should ask patients if they are using laxatives or diuretics (which would be bad).

3:16 Time for Question Four:
Please comment on the potential clinical significance of the increase in heart rate observed in PHEN/TPM treated individuals.

> If approved, please discuss need for monitoring, possible monitoring strategies, and contraindications for use.

3:17 Panelist surprised that heart rates were as low as they were in the study.

3:19 Panelist concerned about the erosion of the public trust every time the FDA approves a drug, but doesn't get it right. Commends the company for getting it right with its efficacy study, but wishes Vivus had done more with safety research. He is encouraged that Vivus is embarking on a study concerning cardiovascular outcomes.

Seems to be a throwback sentiment to GSK's Avandia panel earlier this week.

3:22 Panel now asking about increased risk of stroke. Suggests that the FDA monitor risk post-marketing.

3:25 Panelist wants to make sure that the elderly are included in that at-risk population.

FDA: We are concerned about the long-term effects of high pulse rate. Obese patients frequently have a high heart rate to start rate. Studies should look at continuous heart rate, not just intermittent. Concerned about using the medication in certain populations -- obese diabetics and the elderly.

3:29 Time for Question Five:
Given the doses of topiramate in PHEN/TPM, please comment on whether you believe PHEN/TPM poses a teratogenic risk to the target population for weight loss.

>If you believe it does pose a risk, please comment on how this risk should be managed in women of child-bearing potential if PHEN/TPM is approved.

3:31 Panelist says she's not comfortable with the current state of knowledge regarding pregnancy and drug. Yet, she acknowledges that obesity increases the risks of birth defects and problems during pregnancy.

3:32 Panelist says level of concern is raised by recurring similarities in malformations. Absence of evidence doesn't mean that there isn't an absence of a problem.

3:35 We wouldn't know what a safe level in the breast milk would be. Panelist recommends that the drug should not be used during breast feeding. Panelist is concerned that this will be a highly attractive drug to women of reproductive age. Need more research on drug and breast feeding. Two panelists think that more study needs to be done in regards to pregnancy before the drug can be put on the market.

That is a bad sign for Qnexa. This has been the first really negative discussion regarding any of the questions. "No one wants to conduct a large public health experiment," says panelist.

3:42 Panelist says pregnancy studies are hard to do, especially pre-marketing because of patient numbers. Says this is not a reason not to approve the drug.

FDA: Different studies have come out with different rates of teratogenicity, but studies used higher dosing. Concerned about the number of patients that would be exposed to the drug and might have affected pregnancies.

3:47 Time for Final Question!!!! Time to Vote On Approval!
Based on the current available data, do you believe the overall benefit-risk assessment of PHEN/TPM (QNEXA) is favorable to support its approval for the treatment of obesity in individuals with a BMI ≥30 kg/m2 or ≥27 kg/m2 with weight-related co-morbidities?

Vote: Yes/No/Abstain

If voting yes:
• Please discuss the basis for this recommendation
• Please discuss any labeling recommendations
• Please discuss whether additional studies should be conducted post-approval

If voting no:
• Please discuss basis for this recommendation
• Please discuss what additional studies would be necessary to address an outstanding deficiency/deficiencies

Results:

yes: 7
No: 9
abstain: 0


Panel votes against approval of Qnexa.

3:52 First panelist says he voted in favor of approval and that best use by patients would occur with more information post-marketing.

3:53 Second panelist voted No. Says the drug is effective, but more information is needed. Concerned about the public health consequences. Panelist wants more discussion on REMS

3:57 Third panelist voted yes because of efficacy and the quality of life survey data.

3:58 Fourth panelist voted yes. Because of same reasons as the first panelist.

4:00 Five panelist voted No on safety data. Would have voted yes if there was further follow-up beyond one year.

4:01Sixth panelist voted no for reasons mentioned earlier.

Well, you get the idea. Panelists were split on whether Qnexa was worth it for patients, but in the end the panelists wanted more information on the safety concerns.

Thank you all for following Minyanville's Live Blog today of the advisory panel. Please join us again in September and December for the panels on Arena and Orexigen, respectively. I appreciated all of your comments, questions, tweets, and retweets. Stop back at Minyanville tomorrow for further analysis of today's panel and how the outcome will affect Vivus, Arena, and Orexigen.

~ Lisa LaMotta














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