Arena Pharma's Data Points to Blockbuster Weight-Loss Drug Approval
By Reza Ganjavi - April 26, 2012 | Tickers: ARNA, AVNR, DNDN, LLY, VVUS | 46 Comments
Reza is a member of The Motley Fool Blog Network -- entries represent the personal opinions of our bloggers and are not formally edited.
A recent article, "American Obesity Epidemic Much Worse Than CDC Believes," highlighted the seriousness of obesity as a disease, and warned that its prevalence is much higher than Centers for Disease Control's current estimates.
Obesity drugs are a hot topic these days. In doing research about obesity drug stocks I have been really impressed by the number of doctors who are confident that Arena's lorcaserin will be approved by the AdComm on May 10th and then the FDA on June 27, 2012.
Dr. Steven Vig an internal medicine doctor in Arizona who has many obese patients spoke about Arena (NASDAQ: ARNA) and compared it to Dendreon (NASDAQ: DNDN)
I sat on a pharmacy and therapeutics committee (for Intergroup/Healthnet) for 25 years and I have reviewed many drugs. I can say that I would, without a doubt, approve lorcaserin if this drug came to me on a P and T committee evaluation. I have read extensively about the medical aspects of lorcaserin over the last 3 years and I strongly believe that it should be available for doctors to use. There are indeed similarities to the stock action a few years ago on Dendreon. Provenge was initially turned down by the FDA, but later approved after additional studies were done. Arena has done the work requested by the CRL , and I believe that lorcaserin should be approved by the FDA on or before 27 June 2012.
Let's put it this way, I have not heard a single doctor who is familiar with lorcaserin to say it shouldn't be approved. At the same time, as in with every other pre-PDUFA biopharama the stock's fluctuations has been extreme, and attempts to effect the price and sentiments abundant. The only people who have been vocal about lorcaserin not getting approval are a journalist working for Jim Cramer who's on record for saying when in a hedge fund mode "truth is so against your view that it's important to create a new truth, to develop a fiction", and a hedge fund manager.
Let's have a look at the facts as elegantly spelled out by Dr. Daniel P. Lopez, M.D., F.A.C.O.G., an obstetrician and gynecologic surgeon in Los Angeles who is very interested in lorcaserin and believes FDA will approve it by the June PDUFA date, because endocrinology is a major field in the specialty of gynecology, and obesity is a significant problem in both obstetrics and gynecology.
1. Mammary Cancer risk: PWG findings settled this - only risk of mammary adenocarcinoma was in high dose group.
2. Mammary benign tumor risk - fibroadenomas: even thought there was an increased incidence in rat tumors this will be explained both by the high incidence of fibroadenomas in rats in general and the prolactin MOA studies. If they have Dr. Russo as an expert to discuss this it then there there should be no problem. Even if he is not present there is enough information already present in the toxic pathology literature to use as supporting evidence.
3. Rat astrocytoma cancer risk: the inappropriate findings on the first FDA BD and the CSF findings resolved this. This should pose no concerns.
Note: Most importantly, there were no increase in either benign or malignant tumors in any of the clinical studies - this is very important.
4. Valvulopathy: The receptor study submitted in the first NDA was supplemented with data that shows there is no risk of valvulopthy associated with lorcaserin. The experiments confirmed that lorcaserin has greater potency at the serotonin 2C receptor than at the serotonin 2A or 2B receptor. Furthermore, the results demonstrated that lorcaserin's potency is closer to the reference compounds that do not cause valvulopathy that those that do.
We have not yet seen the data from the valvulopathy study so we have to go with what's in the company's SEC filings which indicates no valvulopathy risk. I anticipate the data will be released before the AdComm or as part of the Briefing Documents but with any unseen data there-s always a risk.
5. MACE events: the BLOOM - DM study will present very positive findings with regard to this concern - that is, its prevention of major complication associated with both diabetes and obesity - the positive effects of weight loss and decrease in type 2 DM should and will likely be discussed.
6. Efficacy: I believe that Arena is more prepared to discuss the per protocol study findings which demonstrate significant weight loss on those who stayed on lorcaserin, and the key is that it was carried out for two years. Furthermore - it did meet the FDA guidelines.
So to summarize the answer in one sentence - there are no scientific issues that should be of concern, there is overwhelming evidence of both safety and benefit - the only concern would be the bias of certain individuals.
I am personally not concerned about the bias factor. If it's true and if it shows up, there are enough panel members to neutralize it, and it will be obvious and will not bode well for them. In Provenge's AdComm there was clearly a bias by two doctors who ended up being heavily scrutinized and the accusations were further than intellectual bias into financial conflict of interest.
Other companies have raised issue proactively. Prior to its February 3, 2009 AdComm for Prasugrel, Eli Lilly (NYSE: LLY) requested that a panel member (who may be part of the Arena AdComm as well and was on Arena's 2010 AdComm) be removed from the panel. According to an article on heart.org:
...the drug's sponsor called the agency to question the inclusion of Dr Sanjay Kaul (Cedars-Sinai Medical Center, Los Angeles, CA) on the Cardiovascular and Renal Drugs Advisory Committee. In an interview today, FDA officials insisted that the call from Lilly had no bearing on their decision to exclude Kaul but acknowledged "mistakes" were made. Acording to Dr John Jenkins, FDA director of the Office of New Drugs... "...they [Lilly] were raising questions about whether he had an intellectual bias that would preclude him from being a fair member of the committee." Days later, Kaul, an expert in vascular physiology and an outspoken critic of prasugrel, was dropped from the committee. The panel subsequently went on to unanimously recommend approval of prasugrel...
The data speaks for itself and points to a blockbuster approval.
In phase III studies, 47.5% of patients who took Lorcaserin lost at least 5% of their weight versus 20.3% for placebo patients. Of those completing the studies, 63.9% lost greater than 5% of their weight, 34.7% lost greater than 10% of their weight, and the top 25% lost over 16.7%. The average completer weight loss was 26 pounds or 8.2%. It has been scientifically proven that even a 5% drop in weight can result in meaningful improvements in overall health.
The huge short interest may wish to ignore these facts but they did the same thing with Dendreon, and Avanir (NASDAQ: AVNR) and even with Vivus (NASDAQ: VVUS). The same journalists who were basing ARNA were bashing these other drugs too. DNDN and AVNR both got FDA approval and VVUS got a positive AdComm vote. Generex Biotechnology sued TheStreet & Feuerstein for $250M for "spreading categorical falsehoods".
Some investors believe VVUS is a competitor of ARNA but the pie is huge first of all, and secondly, doctors will probably use both lorcaserin and in some cases Qnexa as follow on therapy, but given lorcaserin's clearly superior safety profile, Arena should capture a huge share of the huge obesity market.
Lorcaserin is far safer than Qnexa (see new FoxNews video on Qnexa's poor safety) and given the fact that Qnexa's review has been delayed by three months, it seems that Lorcaserin will be first to market. With manufacturing facilities ready to go (in Switzerland) and a strong partner already signed up, we seem to be geared up to witness a blockbuster approval.
By Reza Ganjavi - April 26, 2012 | Tickers: ARNA, AVNR, DNDN, LLY, VVUS | 46 Comments
Reza is a member of The Motley Fool Blog Network -- entries represent the personal opinions of our bloggers and are not formally edited.
A recent article, "American Obesity Epidemic Much Worse Than CDC Believes," highlighted the seriousness of obesity as a disease, and warned that its prevalence is much higher than Centers for Disease Control's current estimates.
Obesity drugs are a hot topic these days. In doing research about obesity drug stocks I have been really impressed by the number of doctors who are confident that Arena's lorcaserin will be approved by the AdComm on May 10th and then the FDA on June 27, 2012.
Dr. Steven Vig an internal medicine doctor in Arizona who has many obese patients spoke about Arena (NASDAQ: ARNA) and compared it to Dendreon (NASDAQ: DNDN)
I sat on a pharmacy and therapeutics committee (for Intergroup/Healthnet) for 25 years and I have reviewed many drugs. I can say that I would, without a doubt, approve lorcaserin if this drug came to me on a P and T committee evaluation. I have read extensively about the medical aspects of lorcaserin over the last 3 years and I strongly believe that it should be available for doctors to use. There are indeed similarities to the stock action a few years ago on Dendreon. Provenge was initially turned down by the FDA, but later approved after additional studies were done. Arena has done the work requested by the CRL , and I believe that lorcaserin should be approved by the FDA on or before 27 June 2012.
Let's put it this way, I have not heard a single doctor who is familiar with lorcaserin to say it shouldn't be approved. At the same time, as in with every other pre-PDUFA biopharama the stock's fluctuations has been extreme, and attempts to effect the price and sentiments abundant. The only people who have been vocal about lorcaserin not getting approval are a journalist working for Jim Cramer who's on record for saying when in a hedge fund mode "truth is so against your view that it's important to create a new truth, to develop a fiction", and a hedge fund manager.
Let's have a look at the facts as elegantly spelled out by Dr. Daniel P. Lopez, M.D., F.A.C.O.G., an obstetrician and gynecologic surgeon in Los Angeles who is very interested in lorcaserin and believes FDA will approve it by the June PDUFA date, because endocrinology is a major field in the specialty of gynecology, and obesity is a significant problem in both obstetrics and gynecology.
1. Mammary Cancer risk: PWG findings settled this - only risk of mammary adenocarcinoma was in high dose group.
2. Mammary benign tumor risk - fibroadenomas: even thought there was an increased incidence in rat tumors this will be explained both by the high incidence of fibroadenomas in rats in general and the prolactin MOA studies. If they have Dr. Russo as an expert to discuss this it then there there should be no problem. Even if he is not present there is enough information already present in the toxic pathology literature to use as supporting evidence.
3. Rat astrocytoma cancer risk: the inappropriate findings on the first FDA BD and the CSF findings resolved this. This should pose no concerns.
Note: Most importantly, there were no increase in either benign or malignant tumors in any of the clinical studies - this is very important.
4. Valvulopathy: The receptor study submitted in the first NDA was supplemented with data that shows there is no risk of valvulopthy associated with lorcaserin. The experiments confirmed that lorcaserin has greater potency at the serotonin 2C receptor than at the serotonin 2A or 2B receptor. Furthermore, the results demonstrated that lorcaserin's potency is closer to the reference compounds that do not cause valvulopathy that those that do.
We have not yet seen the data from the valvulopathy study so we have to go with what's in the company's SEC filings which indicates no valvulopathy risk. I anticipate the data will be released before the AdComm or as part of the Briefing Documents but with any unseen data there-s always a risk.
5. MACE events: the BLOOM - DM study will present very positive findings with regard to this concern - that is, its prevention of major complication associated with both diabetes and obesity - the positive effects of weight loss and decrease in type 2 DM should and will likely be discussed.
6. Efficacy: I believe that Arena is more prepared to discuss the per protocol study findings which demonstrate significant weight loss on those who stayed on lorcaserin, and the key is that it was carried out for two years. Furthermore - it did meet the FDA guidelines.
So to summarize the answer in one sentence - there are no scientific issues that should be of concern, there is overwhelming evidence of both safety and benefit - the only concern would be the bias of certain individuals.
I am personally not concerned about the bias factor. If it's true and if it shows up, there are enough panel members to neutralize it, and it will be obvious and will not bode well for them. In Provenge's AdComm there was clearly a bias by two doctors who ended up being heavily scrutinized and the accusations were further than intellectual bias into financial conflict of interest.
Other companies have raised issue proactively. Prior to its February 3, 2009 AdComm for Prasugrel, Eli Lilly (NYSE: LLY) requested that a panel member (who may be part of the Arena AdComm as well and was on Arena's 2010 AdComm) be removed from the panel. According to an article on heart.org:
...the drug's sponsor called the agency to question the inclusion of Dr Sanjay Kaul (Cedars-Sinai Medical Center, Los Angeles, CA) on the Cardiovascular and Renal Drugs Advisory Committee. In an interview today, FDA officials insisted that the call from Lilly had no bearing on their decision to exclude Kaul but acknowledged "mistakes" were made. Acording to Dr John Jenkins, FDA director of the Office of New Drugs... "...they [Lilly] were raising questions about whether he had an intellectual bias that would preclude him from being a fair member of the committee." Days later, Kaul, an expert in vascular physiology and an outspoken critic of prasugrel, was dropped from the committee. The panel subsequently went on to unanimously recommend approval of prasugrel...
The data speaks for itself and points to a blockbuster approval.
In phase III studies, 47.5% of patients who took Lorcaserin lost at least 5% of their weight versus 20.3% for placebo patients. Of those completing the studies, 63.9% lost greater than 5% of their weight, 34.7% lost greater than 10% of their weight, and the top 25% lost over 16.7%. The average completer weight loss was 26 pounds or 8.2%. It has been scientifically proven that even a 5% drop in weight can result in meaningful improvements in overall health.
The huge short interest may wish to ignore these facts but they did the same thing with Dendreon, and Avanir (NASDAQ: AVNR) and even with Vivus (NASDAQ: VVUS). The same journalists who were basing ARNA were bashing these other drugs too. DNDN and AVNR both got FDA approval and VVUS got a positive AdComm vote. Generex Biotechnology sued TheStreet & Feuerstein for $250M for "spreading categorical falsehoods".
Some investors believe VVUS is a competitor of ARNA but the pie is huge first of all, and secondly, doctors will probably use both lorcaserin and in some cases Qnexa as follow on therapy, but given lorcaserin's clearly superior safety profile, Arena should capture a huge share of the huge obesity market.
Lorcaserin is far safer than Qnexa (see new FoxNews video on Qnexa's poor safety) and given the fact that Qnexa's review has been delayed by three months, it seems that Lorcaserin will be first to market. With manufacturing facilities ready to go (in Switzerland) and a strong partner already signed up, we seem to be geared up to witness a blockbuster approval.