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I have been trading equities since 1998. Currently a full time endodontist in NYC.
  • Why Lorcaserin Will Be Approved 19 comments
    May 2, 2012 4:56 PM | about stocks: ARNA, VVUS

    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.

      Stocks: ARNA, VVUS
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    Comments (19)
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    • silverant
      , contributor
      Comments (71) | Send Message
       
      Two Things: in the same breath you say "...Qnexa.... is.... being used right now. The FDA advisory board had just recommended it for approval by 20-2 in February." and "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."

       

      The heart attacks were viewed as not associated with the drug, and it is "being used right now." How long has it been used? Many years. And the FDA is worried? I don't think so, not about the drug, but about assuaging public concern and opinion going forward. Which brings me to my final point - all obesity drugs will be subject to structured post-approval studies/monitoring of some kind, including Lorcaserin. (see the minutes of the March ADCOM)

       

      Disclaimer: I am long both ARNA and VVUS, and this should not be viewed as a disparaging rebuttal of Lorcaserin. Also, I hope this article on the benefits of Lorcaserin is widely read, spiking the PPS beyond $3.00 tomorrow. So thanks.
      2 May 2012, 06:04 PM Reply Like
    • krap_buster
      , contributor
      Comments (289) | Send Message
       
      silverant- we see it this way. Americans are demanding new and improved drugs to combat the failing war on obesity. Lorcaserin is the only true novel weight loss treatment currently up for FDA review, and government last Fall made it clear to FDA it is time for new novel treatments. While Qnexa streamlines the existing coumpund found independently in generics which is a plus, the ingredients are nothing new as treatment, and have been available for a long time by any physician willing to prescribe. Jury is still out on what difference Qnexa will have on the marketplace especially with concern for women of child bearing years. As for post studies ARNA management has the leg up for now with enough time to have prepared for adcom next week following March Weight Loss Panel vote and update, and sure they are ready with a backup plan should FDA ask for one.
      2 May 2012, 08:19 PM Reply Like
    • silverant
      , contributor
      Comments (71) | Send Message
       
      That's fine - I can see that way too, but the piece is full of bullshit and that I don't like. Naturally, I visit both message boards frequently. On the VVUS board confidence abounds, on the ARNA board there exists knee-jerk reactions to both positive and negative articles, with histrionics that cannot be equate with anything else other than fear, as if down deep the entire board senses an FDA rejection. Very sad.
      2 May 2012, 09:49 PM Reply Like
    • M Allen
      , contributor
      Comments (59) | Send Message
       
      Great analysis. The first adcom was sabotaged by the FDA's surprise cancer issue. Funny they failed to mention this concern prior to allowing ARNA to carry out phase three trials on 8000 patients. They also combined malignant and non malignant tumors in order to achieve statistical significance.

       

      If you doubt bias listen to Coleman during the 2010 ARNA adcom. Then listen to him durring the VVUS 2010 adcom. Perhaps he was just helping his x boss who just happens to be running the VVUS trials.
      2 May 2012, 06:13 PM Reply Like
    • ARNA Investor
      , contributor
      Comments (107) | Send Message
       
      I agree with M Allen. The FDA had no problem blindsiding ARNA the first time around. They won't hesitate to do it again. Still has a little runup left but not much. Should be a safe short by Monday.
      2 May 2012, 06:35 PM Reply Like
    • PhillyDan
      , contributor
      Comments (418) | Send Message
       
      The FDA will not blindside Arena. Take it to the bank and don't get hung up on the BD's, wait until the panel. BD's most always have a negative bent to them.
      3 May 2012, 06:13 PM Reply Like
    • justjohnny
      , contributor
      Comments (44) | Send Message
       
      Efficacy is not established until you conduct the following trials:
      1. Topomax vs. Lorcaserin (unnecessary)
      2. Topo-Phen vs. Lor-Phen (practical application)

       

      Just because Topo has been around for years doesn't mean its a more effective appetite suppressant than lorcaserin. And if topo-phen combined efficacy is only slightly higher than lorcaserin how would a lor-phen combined result compare.
      You cannot compare an appetite suppressant (lorcaserin) to a combination of an appetite suppressant and a fat burner (topomax +phentermine = Qnexa)  
      Of course the FDA must approve lorcaserin in order to move the objective forward. Which is exactly why they will. Too many people know what the FDA is up to this time around.
      What possible motivation would the FDA have for crippling this type of innovation - even Coleman and Kaul can't sit on it anymore.
      Bet the farm on ARNA the world needs it and these dopes (FDA) can't make another spectacle of themselves with EMA part of the equation. This time they will not f around.
      2 May 2012, 06:55 PM Reply Like
    • yousaidwhat
      , contributor
      Comments (23) | Send Message
       
      What makes you think "The FDA delayed Qnexa to give Lorcaserin, the safer of the two, a head start?" As I'm long on ARNA only I would like to believe your statement is true but I seriously doubt Arena was a factor behind their decision.
      2 May 2012, 07:20 PM Reply Like
    • YeahOkay
      , contributor
      Comments (2) | Send Message
       
      Nothing new. Also it's very apparent that you are biased. Please review your data before posting, as some things are inaccurate.

       

      Things that I found inaccurate or should be further elaborated on:

       

      -You think the Qnexa heart rate, birth defects, suicidal tendencies, BCP side effects, and memory loss are worrying the FDA, yet at the end you still state they will get approval. You don't state any #'s or %'s, just words. Obviously it's not that much cause for concern after all, or you think the FDA is corrupt and will approve it. In that case then Lorc is doomed to fail because of the corrupt FDA will just deny it.
      -When you talk about the efficacy, you state the time frame of the BLOOM and BLOSSOM studies, yet you leave out the most recent BLOOM-DM time frame.
      -Yes they met one of the criteria set up by the FDA, but remember its marginal as stated repeatedly throughout the panel review. Thus leads to the case of risk vs efficacy which you do not bring up at all.
      -Does it concern you at all, because it does for me, that they only used 600, 300 split, patients in this study? This is a small group of numbers.
      -Again secondary endpoints, post more data, not useful with just words.
      -If you are going to nearly quote or paraphrase someones ideal (Ron Paul), cite it. This is the first I'm hearing of this.
      -EMEA has higher standards of efficacy than the FDA.
      -EMEA DID NOT reject Qnexa, it's on hold as they are waiting for Vivus to respond to a concern.
      -5 heart attacks in Qnexa, not all were Qnexa related. I did not do in depth research on Q but I know that's not all Qnexa related.
      -You should state not a single case in the 4000 patients that took Lorc, you make it sound as if it was 8,000 patients. In reality it was half/half of phase 3 #'s.
      -You act as if Lorc has no side effects, it does have side effects, and it would be fair to state them.

       

      Basically what I get from this is a biased pumper article. If you read my posts here recently, you will know that I am a ARNA supporter, but I don't appreciate false information on any end.
      3 May 2012, 12:45 AM Reply Like
    • PhillyDan
      , contributor
      Comments (418) | Send Message
       
      Sorry Qnexa pumper. Qnexa had 17 side effects that were greater than placebo, 17 side effects with a DOR of 18% on the high dosage of Q for side effects.

       

      Yes, lorcaserin has side effects but the major one is a mild headache that goes away within a few days.

       

      Yes EMEA has higher standards of efficacy but also using sub-group analysis as an alternative and in case you haven't heard, the EMEA has already stated to Arena that lorcaserin meets their weight loss guidelines. Otherwise, they would not have accepted the MAA from Arena. Listen to the CC where a analyst who obviously never read the EMEA's guidelines asked this question and was told what I have stated.
      3 May 2012, 05:12 PM Reply Like
    • ATLnsider
      , contributor
      Comments (48) | Send Message
       
      Drendo4u,

       

      I believe that there is enough room in the marketplace for several new drugs to treat obesity. I also believe that the marketplace will ultimately pick winners and losers. I don't have anything against Arena, its stockholders or its new obesity drug, Lorcaserin. As a Vivus stockholder and a believer in its drug Qnexa, I do have some different opinions on some of the statements that you made in this article.

       

      Arena's new obesity drug should be evaluated based upon its own efficacy and safety data. You should not have to resort to trying to make Lorcaserin look good by trying to make Qnexa look bad.

       

      However, I wanted to mention some of the comments and points that you made that I do agree with. I agree with the following statements or points that you made:

       

      (1) For many people, diet and exercise alone, is not an effective way to lose weight, and keep the weight that was lost from coming back.

       

      (2) Patients who were treated with Qnexa lost significantly more weight on average than those patients treated with Lorcaserin.

       

      (3) Qnexa had a very positive FDA Advisory Committee (Adcom) meeting and the Adcom panel voted 20 to 2 in favor of approving Qnexa.

       

      (4) The FDA will likely approve Qnexa on or before July 17, 2012.

       

      (5) Qnexa is a combination of two (2) different drugs that are already approved by the FDA, Phentermine and Topiramate.

       

      Now, I would like to mention some of the statements and points that you mentioned that I do not agree with, along with providing some data to verify my positions. First, I do understand and acknowledge that most of the data I am referencing regarding Lorcaserin comes from its old FDA Lorcaserin advisory committee meeting that was held back in 2010. I do realize that the FDA will be releasing some new briefing documents soon for Lorcaserin's upcoming Adcom on May 10, 2012, and as a result, some of this data may be updated soon .

       

      (1) You stated that you think that the reason that the Qnexa PDUFA date was extended from April 17, 2012 to July 17, 2012 was because "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".

       

      However, there are several facts I wanted to mention to correct these statements you made. The first facts are stated in the following Vivus press release regarding the Qnexa PDUFA extension:

       

      http://bit.ly/HtgipA

       

      This press release states the following reason for the Qnexa PDUFA date extension:

       

      "On April 4, 2012, following the FDA's request, VIVUS submitted the Qnexa Risk Evaluation and Mitigation Strategy (REMS), which was considered a major amendment to the NDA. The submission consisted of proposed REMS materials. Since the receipt date was within three months of the user fee goal date, the FDA is extending the PDUFA date by three months to provide time for a full review of the submission."

       

      "The Qnexa REMS submission is comprehensive, with materials based on ongoing feedback from the FDA since our advisory committee meeting in February," stated Leland F. Wilson, chief executive officer of VIVUS. "We look forward to finalizing our REMS with the FDA while we move forward with our commercialization plans."

       

      As you can see, the PDUFA extension had nothing to do with concerns about increased heart rate, birth defects, suicidal tendencies or memory loss. The FDA needed more time to review the REMS that were submitted by Vivus on April 4, 2012. Most analysts believe that this was a positive indication for Vivus because it shows that the FDA and Vivus are focused on post-approval, post-marketing and commercialization issues. Most analysts also believe that if the FDA had the concerns you mentioned, the FDA would have issued a CRL instead of asking Vivus to prepare and submit REMS because REMS are only needed for an approved drug. Lastly, most analysts agree that the Qnexa REMS will primarily focus on pregnant women, women who become pregnant, and women who are planning to become pregnant. Vivus does not want pregnant women to take Qnexa, and the REMS will target it's messages toward women of child-bearing potential (WOCBP) and pregnant women to warn them about the slight risk of cleft lip.

       

      In addition, during clinical trials, Qnexa only showed a slight increase in heart rate of less than 1 beat per minute (0.6) at the mid-dose (the recommended dose) , and only 1.6 beats per minute at the high-dose. Most analysts agree that this is not a signal of excess cardiovascular risk, and the FDA will be satisfied with a post-approval CVOT for Qnexa.

       

      (2) You suggested that the FDA did not have any issues are concerns with Lorcaserin in regards to neuro-psychiatric cognitive disorders, including: memory loss or suicidal thoughts or tendencies. However, take of look at page 5 of the FDA Lorcaserin Adcom Briefing Document:

       

      http://1.usa.gov/z1MQdl

       

      it states the following: " Neuro-psychiatric and Cognitive-Related Adverse Events: In the phase 3 clinical trials, perceptual- or dissociative-related adverse events were reported by 21% of subjects treated with lorcaserin 10 mg BID compared with 12% of subjects treated with placebo. A wide variety of individual adverse event terms including dizziness, fatigue, paresthesias, and abnormal dreams, contributed to the overall imbalance between treatment groups."

       

      Also, please note this statement on page 117 of this same document:

       

      "Cognitive adverse effects (AEs) were primarily identified from the Phase 3 database, in which AEs such as impairments in attention and memory were seen 3 times as frequently in the lorcaserin 10 mg BID treated group as compared to placebo."

       

      (3) You stated that Lorcaserin did meet the FDA's minimum weight loss efficacy requirements. However, if you look at the FDA Lorcaserin Adcom Briefing Document on page 4 of this document, you will see that the average weight loss for patients on Lorcaserin after one year was only 5.8%. Also, on this same page, you see that the FDA Reviewer states the following: "Therefore lorcaserin did not satisfy the guidance’s mean efficacy criterion. However, the lorcaserin 10 mg BID dose did, by a slim margin, satisfy the categorical efficacy criterion."

       

      Also, this is what the FDA reviewer stated on page 80 of the Lorcaserin FDA Adcom Briefing Document: "However, the placebo-adjusted weight loss was relatively low, compared to the benchmark of 5% described in the February 2007 draft Guidance for Industry: Developing Products for Weight Management. The clinical review division should evaluate whether or not the weight loss associated with Lorcaserin is clinically significant."

       

      The criterion that Lorcaserin did satisfy by a slim margin was average weight loss of at least 3.0% more than the placebo. The average weight loss for patients on the placebo was 2.5%, so Lorcaserin's average weight loss of 5.8 was 3.3% more than the placebo. This barely satisfied the FDA's requirement by 0.3%.

       

      (4) You stated that 5 patients who were treated with Qnexa during clinical trials had a heart attack. However, you failed to also mention that none of these myocardial infarctions or heart attacks were caused by Qnexa. In addition, you also failed to mention that there were also 5 patients who were treated with Lorcaserin during clinical trials who also had a heart attack or myocardial infarction. You can see this fact in the FDA Lorcaserin Adcom Briefing Document on page 230, Table 118, of that same link above.

       

      (5) You stated women of child-bearing potential (WOCBP) who participated in the Qnexa clinical trials were required to take birth control. However, you failed to mention that weight loss drugs are not intended to be used by pregnant women. You also failed to mention that these same group of women were also required to take birth control in the Lorcaserin clinical trials. Take a look at page 236 in the FDA Lorcaserin Adcom Briefing Document, you will see the following stated as requirements for women to be eligible to participate in the Lorcaserin clinical trials:

       

      "Arena Healthy Lifestyle Program:

       

      a. Eligible female patients will be:

       

      non-pregnant, evidenced by a negative serum hCG pregnancy test at Screening and a urine dipstick pregnancy test on Day 1 prior to dosing

       

      - non-lactating

       

      - surgically sterile or postmenopausal, or agree to continue to use an accepted method of birth control during and for at least 3 months after last study medication administration

       

      − Acceptable methods of birth control are: hormonal contraceptives; single barrier method; intrauterine device; surgical sterility for at least 3 months prior to screening for tubal ligation performed laparoscopically; surgical sterility for at least 6 months prior to screening for hysterectomy and/or bilateral oophorectomy; and/or postmenopausal status (defined as at least 2 years without menses).

       

      Abstinence is not considered an acceptable method of birth control for this study."

       

      (6) Phentermine has a long history of usage and was approved by the FDA in 1959. Topiramate also has a long history of usage and it was approved by the FDA in 1996. There were over 10 million prescriptions written for Topiramate, and over 6.5 million prescriptions written for Phentermine during 2011 alone. Phentermine was the most prescribed weight loss drug in the nation, and it was prescribed significantly more than all of the other obesity drugs combined. A large percentage of weight loss patients in the USA are already familiar with Phentermine and its possible side effects.

       

      There are not any unknowns with Phentermine and Topiramate, and both appear to be well-tolerated by current patients. Lorcaserin is a brand new drug that does not have an extensive history of usage in the general population. As you know, obesity is a chronic condition, and some patients could be taking these drugs for years, or even the rest of their life. There are a lot of unknowns with Lorcaserin, including not knowing the effect of long-term usage over several years.

       

      (7) You stated that Arena has addressed the allegations of cancer in rats that were exposed to Lorcaserin. I will withhold any comments or judgment regarding this issue, and I will wait until the new Lorcaserin Adcom briefing documents are released by the FDA prior to May 10th.

       

      (8) You indicated that because of Qnexa's REMS, Lorcaserin may have an advantage because it will be more available and less restricted than Qnexa. However, at this point, we do not know if Arena will be required to file REMS for Lorcaserin, and if they are required to file REMS, we do not know how long the FDA will take to review those REMS. As we have seen with Qnexa, if the FDA does require that REMS need to be submitted and reviewed for Lorcaserin, then that will be considered a significant amendment and the PDUFA will almost always be delayed or extended 90 days. If that is the case, the new PDUFA date for Lorcaserin would be September 27, 2012.

       

      Again, I do believe that there is room in the market for both Qnexa and Lorcaserin. However, at this stage, Qnexa is much further along in the process. I will take a look at the new FDA Lorcaserin Adcom briefing documents for the May 10th Adcom once they are released by the FDA, to get an update on Lorcaserin's efficacy and safety. We will see how the Lorcaserin Adcom panel votes, and then maybe we will see if the FDA will ask for Lorcaserin REMS to be submitted.
      3 May 2012, 01:11 AM Reply Like
    • PhillyDan
      , contributor
      Comments (418) | Send Message
       
      Take a breath.

       

      Regarding (2) above. Not an issue at all. Was it in the CRL issued to Arena? The answer is no! Keep repeating it all you want but not an issue.

       

      (3) Lorcaserin met the categorical weight loss requirement not the mean weight loss requirement but since it is a "either/or" guideline lorcaserin met the FDA's weight loss guidelines. All your other points are worthless keystrokes.

       

      Funny, how you don't mention that lorcaserin is a single agent, Q as we know is a combined agent. How about if we had a study that compared lorc to phentermine alone and the same with topiramate. That is the fairer comparison before you start throwing efficacy data around. BTW, the top responders in both the lorc studies and Q studies had about the same amount of weight loss.

       

      Not here to argue efficacy. Q with two agents had better efficacy compared to placebo. But until there is study comparing the two side by side all of this efficacy talk is meaningless.

       

      4) Again not an issue for Arena at all. This was addressed and again read the CRL that Arena received from the FDA. It was not addressed as an issue.

       

      6) Well if phentermine is so great why are the sales so lousy?
      But who has the patent for LorcPhen as a combination pill? Arena is who. Arena/Eisai will have to do studies of that combination pill before it can come to market.

       

      But, a certain percentage of doctors will write scrips for both phentermine and lorcaserin separately of course which will be fine because as you stated, phentermine has been around a long time.
      In my opinion that pseudo combination will be more effective than Q.
      But again, only a real head to head study is the only fair comparison.

       

      7) Again, you got this wrong. A group of 5 independent pathologists selected and approved in conjunction with the FDA found that they were able to distinguish between malignant and benign tumors. In addition, their re-adjudication showed that the control group of female rats had more malignant tumors than the 7X and 24X THD female rat groups. Only the 82X group had more malignant tumors but that is way above the 25X safety margin that the FDA uses. Why withhold your judgement. Are you implying that these 5 independent pathologists are wrong in their findings?

       

      Recommend you google Dr. Jose Russo and remember him. He is one of the many expert cancer consultants that Arena did use in the development of the MOA studies which showed the causal relationship between lorcaserin and a increase of prolactin in young female rats and the development of tumorigenesis.

       

      But, since the WPG (Working Pathology Group of 5 independent pathologists) found the control group had more malignant tumors then the 7X and 24X drug groups, the real question is what was the MOA (mechanism of action) that caused the malignant tumors in the control group? Very probable that this same MOA caused the malignant tumors in the drug groups!

       

      There were no cancer signals of significance in the human studies.
      Before you respond with well they could still develop a cancer signal, realize that cancer detection has advanced rapidly. In addition, these studies have been completed for a few years now and still no cancer signals.

       

      8) As of Arena's last CC, the FDA did not ask them to do a REMS!
      In addition, they did not ask them to do a REMS in the CRL.

       

      But I will allow that the FDA between the CC and now, could have asked Arena for a REMS.

       

      The point is no matter how you slice it, the Qnexa REMS on access is very restrictive. People will have a problem ordering from a specialty pharma, not that there is a problem with the specialty pharma, but people will view it as a "pain in the butt". Actually I have used a specialty pharmacy and it was not a pain at all.

       

      Actually we do both agree that we have no problem with both Qnexa and Lorcaserin being approved. But Arena is further ahead with getting lorcaserin to market if approved on June 27th.

       

      They have their own manufacturing facility in Switzerland (the author got this wrong, Eisai is the sales, distribution and marketing arm for lorcaserin in the U.S.) with enough API on hand to produce well over 5 billion pills per year. There factory already has been visited and qualified by the FDA.

       

      Eisai has over 550+ salespeople ready to go upon approval.
      In my opinion, lorcaserin will be on pharmacy shelves everywhere within 2 to 3 months of approval and possibly sooner.
      3 May 2012, 05:53 PM Reply Like
    • justjohnny
      , contributor
      Comments (44) | Send Message
       
      Exactly - Philly I wish I could state it as precisely as you have. Exactly !
      3 May 2012, 06:49 PM Reply Like
    • justjohnny
      , contributor
      Comments (44) | Send Message
       
      Dear altnsider,

       

      Topiramate has proven to be an appetite suppressant with limited efficacy that does not pass the FDA guidelines for a weight loss drug, (forget side effects for the moment) so vvus combined it with a fat burner (phen) to boost efficacy.

       

      Phentermine is a well known fat burner that increases adrenal output and thus metabolism.

       

      On the other hand Lorc is an appetite suppressant that did pass the FDA guidelines (the only one) so even though it has marginal efficacy it is still a better suppressant than Topomax. Obviously the 800 lb gorilla is a lor-phen combo. Do you think the FDA will withhold a lor-phen combo from the obese pop. while allowing a topo-phen combo.

       

      By the way topomax is an anticonvulsant with an unknown moa (http://bit.ly/JtleKI) that has been prescribed to primarily epileptics and severe migraine sufferers, so the long term side effects have only been measured in this population - and phen can only be safely prescribed for 12 weeks. So to say the long term safety profile for Q is well known as compared to Lorc- as you do in #6 above is ridiculous.

       

      If the FDA approves topo-phen (which they have not yet) they are telling you that lor-phen is 100% approvable! This is why lorcaserin will be approved by the adcomm next week and likely before June 27 by the FDA.
      3 May 2012, 09:16 AM Reply Like
    • ATLnsider
      , contributor
      Comments (48) | Send Message
       
      JustJohnny,

       

      I appreciate your response back to me regarding my comments. You made some statements that I would like to correct, along with the proof to backup my positions:

       

      (1) You stated that Phentermine is FDA approved and it is used to boost metabolism, and Topiramate is an appetite-suppressant. Also, you stated that Phentermine is an . However, there are a couple of corrections I wanted to make regarding these statements. Phentermine is also an appetite suppressant, and it is currently the most prescribed weight loss drug on the market today. Take a look at slides 27 and 28 in this FDA presentation dated March 28, 2012:

       

      http://1.usa.gov/HAP40s

       

      As you can see during 2011, there were over 2.5 million patients taking Phentermine in the USA alone. Phentermine was the most prescribed weight loss drug in the nation, and it was prescribed significantly more than all of the other obesity drugs combined. You can also look at slides 36 and 44 in this presentation.

       

      In addition, on page 3 of the Vivus Qnexa Adcom Briefing Document:

       

      http://1.usa.gov/HORACN

       

      you can see that there were over 6.5 million prescriptions written for Phentermine and over 10.0 million prescriptions written for Topiramate during 2011 alone.

       

      Phentermine has a long history of usage since 1959, and a large percentage of weight loss patients in the USA are already familiar with Phentermine and its possible side effects. There are not any unknowns with Phentermine, and it appears to be well-tolerated by current patients. Phentermine is one of the ingredients in Qnexa. The average weight loss from Phentermine by itself is higher than the average weight loss with Lorcaserin. As you can see in the Vivus Qnexa Adcom Briefing Document on page 36, the average weight loss for Phentermine alone is about 6.5% and the average weight loss for Lorcaserin was only 5.8%. There would not be any reason for a patient to switch from Phentermine to Lorcaserin because of Lorcaserin's comparatively low efficacy and its possible unforeseen adverse side effects.

       

      (2) You stated that Arena will be able to combine Lorcaserin with Phentermine for better efficacy (Lor-Phen). However, as you know, in order to change a drug by adding a new ingredient or combine it with another drug, Arena will have to go through a new drug approval process all over again, just like Vivus did with Qnexa (Topiramate / Phentermine). Arena would have to conduct pre-clinical and clinical trials, run animal test, conduct human test, and then file a new NDA. This process will cost tens of million of dollars, and it take several years.

       

      Also, for a doctor to arbitrarily mix-and-match and combine different obesity drug medications, would be asking for trouble. There would be a tremendous amount of liability exposure, as was the case with Fen-Phen. These medications would need to be tested to determine how they would interact together, and to see if they cause any significant adverse events. There would not be any need for a doctor to do this when Qnexa is available, because Qnexa is a combination of two drugs already approved by the FDA. Phentermine and Topiramate are both known quantities, and both have been studied for decades. Lorcaserin is an unknown quantity. The FDA, patients and physicians do not know what known and unknown adverse events will occur with long-term usage of Lorcaserin, especially combined with Phentermine.

       

      (3) You stated that the long-term effects of Topiramate have not been studied, but as you know obesity is a chronic condition that could last for a person's lifetime, just like epilepsy and migraines. This means that for some patients, they may have been taking Topiramate since it was first approved by the FDA in 1996. That's over 16 years ago. There is a tremendous amount of long-term data available for Topiramate since 1996.

       

      (4) Many Qnexa detractors, and some Arena longs, overstate and exaggerate the safety profile of Topiramate / Phentermine (Qnexa). They say that there will be a slew of cardiovascular issues and birth defects. However, the facts do not support this assertion.

       

      I do acknowledge that the FDA did change the Topiramate to a Class D drug and they strengthened the warning for pregnant women. I also know about the results of the following studies: FORTRESS, CDC / Slone, the Denmark Study, the UK Pregnancy Registry, and the North American Ant-Epileptic Drug (NAAED) Registry.

       

      All of these studies only showed a slight signal for cleft lip, not any other major congenital malformations. Even the incidence rate for cleft lip was extremely low, and the average dose of Topiramate in these studies were much higher than all of the Qnexa doses.

       

      You would think that even with Phentermine, the ingredient that may have caused an average increase in heart rate of 0.6 (less than 1 beat) beat per minute at the mid-dose in the Qnexa clinical trials, there would be dozens of instances where Phentermine caused adverse cardiovascular issues since 1959, but that is not the case.
      3 May 2012, 01:01 PM Reply Like
    • PhillyDan
      , contributor
      Comments (418) | Send Message
       
      You will be proven quite wrong about a certain percentage of doctors treating obesity not using phentermine in combination with phentermine. They have been doing it with phentermine and topiramate and most that started doing it had no idea of what the mix would do. Yes, I'm glad you mentioned the liability issue, that will more than apply to Qnexa. If you think otherwise, then wait and see.
      3 May 2012, 05:58 PM Reply Like
    • JD Connell
      , contributor
      Comments (26) | Send Message
       
      philly dan,

       

      the fen/phen debacle is a combination of two weight loss drugs. From wiki:
      "The drug combination fenfluramine/phentermine, usually called fen-phen, was an anti-obesity treatment that utilized two anorectics"
      PHETERMINE from wiki:

       

      "People with the following should not use phentermine:
      Are also taking amphetamine (i.e. Adderall, Dexedrine, Vyvanse), bupropion (WellButrin), dexfenfluramine, fenfluramine...."

       

      anorexics

       

      LORCASERIN from wiki:
      "Lorcaserin (APD-356, trade name Lorqess[1][2]) is a weight-loss drug developed by Arena Pharmaceuticals. It has serotonergic properties and acts as an anorectic.
      Lorcaserin is a benzazepine with a structure similar to dexfenfluramine, an anorectic drug that was withdrawn because of cardiovascular side-effects."

       

      No sane doctor will risk combining lor/phen WITHOUT there being safety evaluations and approval from the FDA. Otherwise he/she could be basically prescribing a fen/phen and risking a 30% increase in valvulopathy.

       

      QNEXA from wiki:
      Phentermine is an appetite suppressant and stimulant of the amphetamine and phenethylamine class. Topiramate is an anticonvulsant that has weight loss side effects.
      9 Jun 2012, 02:28 PM Reply Like
    • Sanna
      , contributor
      Comments (2) | Send Message
       
      Derndo4u, thank you for your unbiased article. It is good to see that someone stating the facts without taking sides. I agree with M Allen, ARNA Investor, and Johnny when it comes to efficacy you cannot compare apples (Lorcaserin) with oranges (Qnexa which is a combination o two generic Drugs, Topomax & Phentermine ). Since lorcaserin a new novel appetite suppressant it's efficacy and safety should be compared to Topomax. Or the efficacy & safety of the combination of Lorcaserin & Phentermine compared to Qnexa. Now, the 3 Phase III trials of Lorcaserin demonstratedit is a safe, more effective appetite suppressant than Topomax which cause birth defects, damage heart valve just to name a few of the safety issues Topomax has and Qnexa has as well.
      Ttopomax-Phen combined efficacy is only slightly higher than lorcaserin alone.
      You cannot compare an appetite suppressant (lorcaserin) to a combination of an appetite suppressant and a fat burner (topomax +phentermine = Qnexa)  

       

      The 2010 Adcom was sabotaged by the FDA's surprise cancer in rats issue in order to delay ARNA's approval about two years and give Vivus time to resolve the Qnexa's safety problems and get approve first. How come the FDA told ARNA back in 2007 that the cancer in rats is not an issue and allowed ARNA to failed to carry out 3 Phase III trials on 8000 patients. In addition, the FDA reviewer combined malignant and non-malignant tumors in order to achieve statistical significance which is a big mistake in any statistical analysis.

       

      If you doubt bias listen to Coleman during the 2010 ARNA adcom. Then listen to him durring the VVUS 2010 adcom. Perhaps he was just helping his x boss who just happens to be running the VVUS trials.
      3 May 2012, 12:02 PM Reply Like
    • justjohnny
      , contributor
      Comments (44) | Send Message
       
      Dear Altinsider,

       

      Thank you for your thoroughness. However as you know topo has a long list of horrifying side effects including "stupification", diarrhea, respiratory infections, suicidality and birth defects. This is why dr.'s have nicknamed it "Dopomax". And although compared to epileptic seizure these side effects may be justified - in practice lorcaserin will be a much more highly tolerated drug. This will make it a more effective long term treatment.

       

      And you are correct Arena will have to submit a NDA after it conducts all trials. This will take years and this is exactly what the FDA roadblocked 2 years ago with its bogus rat findings. This time around they will not block it and in fact in my belief they will/should approve ahead of the June 27 PDUFA.

       

      Again Lor-phen is the product, the fact that the FDA was able to delay it in favor of Q (dopo-phen) shows clearly the conflict that exists among present and past FDA personnel. Very likely the EMA will move to fast track, forcing our FDA to follow their lead once again.
      3 May 2012, 06:12 PM Reply Like
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