Arena Pharmaceuticals Investors Smell A Rat
72 CommentsBy Ed Silverman // October 4th, 2010 // 9:21 am
Last month, an FDA advisory committee voted 9-to-5 that the risks of the Lorqess diet drug developed by Arena Pharmaceuticals outweigh the benefits. That move came after concerns about valvulopathy and, in particular, links to malignancies in rats at higher doses, which were revealed in FDA briefing documents and caught some people, including Wall Street analysts, by surprise.
The decision caused a stir among investors and a subsequent controversy about whether Arena properly and promptly disclosed the existence of the tumor data (look here). In comments made to Wall Street analysts following the FDA panel vote, ceo Jack Lief insisted the info was handled correctly. An FDA decision is expected later this month.
Now, a petition has begun circulating the Internet in which the FDA is being asked to override the panel vote and approve the diet pill. The basic case is that the FDA staff made some fundamental mistakes in their analysis. In the FDA briefing documents, the petition contends, an FDA reviewer made “a highly damaging, but incorrect, statement” that “an excess number of malignant tumors developed in female rats with (Lorqess) at doses within seven-fold of the proposed clinical dose of 10mg BID.” In other words, the FDA analysis overstated the case and confused some of the panelists, who were not experts in such matters.
For instance, the petition argues that of the nine panelists who voted ‘no,’ only two did not cite tumors in rats as their main concern. “This suggests seven panelists that voted no might have voted yes if the FDA had provided a toxicology or a carcinogenic expert as support for any concerns the panelists might have had regarding the relevance to human subjects. It is clear that these panelists were confused or uncertain what the rat data showed, and therefore voted no, not based on scientific evidence but rather the fear of uncertainty.
And then there’s this closing appeal to FDA officials: “We believe that the long term effects of this event could result in irreparable damage to the biotechnology and pharmaceutical industry as a whole. The dramatic elevation of concern over rat cancer…has prompted class action lawuits against Arena Pharmaceuticals. Clearly these data were adjusted to show significance in cancer occurrence where none existed. If all pharmaceutical and research firms were to release all toxicological results from their pre-clinical or animal studies to the investing community, equity markets in that industry might cease to exist…”
“The pendulum has swung too far at the FDA if they influence Advisory Committees to vote no for a drug that poses very little risk to the public at large, and certainly less than currently available therapies, and where there is a demonstrable clinical benefit in terms of additional weight loss and reduction in cardiovascular risk factors. This is particularly true if the methodology underlying that influence is unscientific and based upon assumptions that are contrary to accepted scientific knowledge.”
The people who initiated the petition do not reveal their identity and instead preferred to be called ‘Concerned Citizen,’ and they argue that by approving the Lorqess pill, the agency would promote public health, saving untold dollars from the nation’s health costs. Beyond such concerns, however, it is unclear whether the petitioners are tied to Arena or are simply investors who were angered by the FDA review.
In any event, their belief that releasing all toxicology data from pre-clinical or animal studies may fatally damage equity markets may be construed as rather sweeping, if not dramatic. Proper disclosure - and proper analysis - remain desirable. The real issue, of course, was whether the rat data was not only disclosed as it should have been but scrutinized correctly by the FDA staff.
Diet pills, though, are a whole other animal, you’ll pardon the pun. For more than a decade, as you may recall, various diet drugs have been linked to safety issues, most notably the fen-phen weight-loss cocktail, half of which was withdrawn in 1997 over serious links to heart and lung conditions. Given the current environment in which safety is a prime concern, one should not be surprised if the FDA errs on the side of caution. Whether the equity markets then collapse also remains to be seen.
industry insider
There is precedent in this area. The Endocrine/Metabolic Advisory Committe voted in 1996 against approving Meridia based on safety considerations. The FDA ultimately overrode their decision and approved the product. The years were 1995-1997, and all of the problems with Redux were hitting the wires. This may or may not have influenced the FDA’s decision to approve Meridia. Thirteen years later and safety problems have again re-emerged with Meridia. If history repeats itself there is a possibility that the Lorquess diet drug may be approved in similar fashion.
cohor
If you ever wanted a specific, concrete example of out-of-touch Washington bureaucrats making inexplicable decisions that cost Americans their jobs, this event might serve your purposes nicely.
The meeting started with FDA staff admitting lorcaserin had met the agency’s standard for efficacy, with the average patient losing more than 5% of their body weight. Patients also lowered their blood pressure and bad cholesterol by wide margins over the placebo group.
Rather than simply letting the data speak for itself, FDA staff inserted the prejudicial language “by a slim margin” in an effort to change the score after the game had already been played. This betrayed not only an unethical (and illegal) bias on the part of the FDA staff, but a collosal failure to understand scale.
Let’s say you are an African American woman, struggling with her weight at 210 pounds. All other things being equal, you will probably gain another five or ten pounds over the coming year. But if you were taking lorcaserin, you would lose eleven pounds (5%) over that same year. That is a delta of sixteen to twenty-one pounds, and could easily be the difference between developing diabetes and not. Imagine just a small percentage of America’s 80 million obese adults likewise losing weight and dodging hypertension, diabetes and heart disease. Our country would save tens of billions of dollars each year in health care costs.
Not satisfied taking a pass-fail test and transforming it into an ill-considered value proposition, the FDA staff then decided to smear lorcaserin’s safety record. The Advisory Committee was told that rats tested with 82 times the standard human dose had developed breast tumors. With all the concern for scientific objectivity normally seen at a witch trial, FDA staff neglected to tell the panel that lorcaserin had also been tested in mice and rhesus monkeys, and had demonstrated a high degree of safety with no elevated risk of tumors. In fact, no human trials would ever have been allowed were that not the case. Why the FDA staff did not tell the panel this is a question some curious congressman or woman may wish to ask. None of the seven thousand humans tested with the drug over two years showed any elevated cancer risk.
It was a shameful day for the FDA, a bad day for medical science, and a frustrating day for many Americans for whom weight loss therapies are not vanity drugs, but real life and death. It was also a bad day for America’s global leadership in biotech, as many companies will chose to develop their drugs in Europe or Asia, rather than try to negotiate an FDA approval process fraught with unpredictable impropriety and caprice. Our nation relies on government regulatory agencies to remain impartial, transparent and objective. Our personal health and the health of our economy depend on it. The full FDA is scheduled to make a final decision on lorcaserin by October 22nd. Whether the maker, San Diego-based Arena Pharmaceuticals, has three hundred employees or three come October 23rd hinges on the outcome. We hope the FDA will ignore its flawed advisory committee recommendation and make a decision it can be proud of, not one it will have to hide from.
Donna Korell
So pleased to finally see some media attention regarding this serious issue!
industry insider
Cohor, although FDA may follow the Meridia/Fen-Phen argument I cited above and approve the Arena drug, remember that the lifers at FDA will be around for many years after the drug is approved. If lorcaserin produces a post-approval long-term safety problem viz Meridia, next time around it won’t just be a matter of holding Advisory Committee meetings. Dr. Woodcock will be summoned before Henry Waxman’s congressional committee congress sometime later this decade, and the question to her will be as follows:
“Dr. Woodcock, in 1997 CDER went the advice of its own Advisory Commitee and approved Meridia. 13 years later, the SCOUT trial proved that Meridia was indeed the dangerous drug that your own committee advised against approving. You repeated the same decision making process in 2010 with Lorquess, going against your own commitee, and these years later we have another dangerous diet drug on our hands. Apparently your agency didn’t learn their lesson the first time with Meridia. How do you respond?”
My view is that Dr. Woodcock has gazed into that crystal ball and doesn’t like what it shows. For this reason I believe that Arena will not only receive a Non-Approvable letter, it will be a full Non-Approval on 10/22/10. Either scenario will tank the stock and we will be looking at a Going-Out of Business sign on Arena’s front door by end of 2010.
AMMASS
“Given the current environment in which safety is a prime concern, one should not be surprised if the FDA errs on the side of caution. Whether the equity markets then collapse also remains to be seen.”
Yeah, then why did the FDA Reviewer show his bias by favoring VVUS’ Qnexa in an interview on CNN just last week ? It has a much worse safety profile
barton grasshopper
Agree Donna, very well put cohor, &
Thank you ED!!
Ardeis Scott, MD
What the petition is asking for is a thorough review of Arena’s Advisory Panel process where it is clear biased comments were made by Dr. Colman and others. Also the FDA manipulated the data in a negative way by combining benign and malignant tumors to give the appearance of a statistical occurrence of cancers in male rats at 55x the equivalent human consumption.
Second, the panel had no animal research or oncology expertise so naturally the members as in their own words felt scared and confused.
A demand for approval is not the purpose of the petition but rather a fair unbiased review or Lorcaserin where science not emotion dictates approval.
Runa
As per your article the petition is anonymous then ARNA and SEC has the name and Addresses of those shareholders and they can easily be contacted and take the survey of their petition. I am one of them and use alias and ready to sign my name on petition. FDA decision was premeditated and completely wrong. It is clear that these panelists were confused or uncertain what the rat data showed, and therefore voted no, not based on scientific evidence but rather the fear of uncertainty.
I am with the group that insists the investigation and asking that FDA to override the panel vote and approve the diet pill. The basic case is that the FDA staff made some fundamental mistakes in their analysis. In the FDA briefing documents per the petition. It is our strong contention that, an FDA reviewer made “a highly damaging, but incorrect, statement” that “an excess number of malignant tumors developed in female rats with (Lorqess) at doses within seven-fold of the proposed clinical dose of 10mg BID.” In other words, the FDA analysis overstated the case and confused some of the panelists, who were not experts in such matters.
FDA had al the opportunity during the all phases of clinical trail and at the time of accepting NDA. Why last minute they come out with the language that is so bias and damaging to the ARNA investors? This definitely needs investigation.
industry insider
I’ve worked with and observed Dr. Eric Coleman’s work at FDA over two decades. I disagree with some of his views, but he is very highly respected within the agency, and the petitioners will be hard pressed to overcome his recommendations.
industry insider
I just checked ARNA’S balance sheet and free cash flow. Given the n=300 employees and average pharma salaries, it appears that without approval or a new round of financing they have enough cash on hand to meet payroll through end-of-January, 2011.
Kollam
Surely Dr. Colman is kept at a high esteem in FDA. Otherwise, he will not be in charge. But we are human and make mistakes. It is good that we have knowledgeable people around us to point out our mistakes so that we can correct the mistakes. FDA should be made aware of the mistakes so that it can remedy the situation. The petition is just that, rasing concern about the proceedings, false interpretation of good data, bias or preferential treatment, lack of expert in the AC panel to autheticate data, etc, etc.
Significant financial commitments were made by the company and the investors by trusting the FDA. Now is the time for FDA to prove that it stands for science and truth.
The DirtyRat
It seems that the author of the briefing doc’s as well as the person who did the summary, especially Mr. Colman, need to be put under the microscope.
After the Qnexa panel said no…Mr. Colman made specific reference to being “surprised” at the outcome and even went so far as to be on CNBS..to also make use of public forums. Being HEAD of his dept and he should know better…making BIASED statements is UNethical. I to belong to the group that brought this petition to bare.
Saying….”by a slim margin” or “I wouldn’t want to put my name…” and then “have to pull the drug.”
CLEARLY misstatements and PERSUASIVE admission that they, FDA or others, DON’T want this drug approved.
Qnexa pumped the efficacy….but the safety dangers were running a muck and deserved it’s outcome. But to dig under 5 miles of rock just to find something that NO HUMAN would be able to bare with a dosage 50+ NORMAL and use it as a means to disgrace Arena for their 10..TEN years of work is..is a flat our disgrace to our country and the FDA dept.
You might as well put a cork in ANY research for obesity in our country. This is a VERY SERIOUS U.S. issue, obesity, as has been our financial one…and look how it’s being treated. Ten years and ONE BILLION $$$$ thrown away in 8 hours of discussion to where panel members couldn’t make an EDUCATED and rational decision because those that WROTE the briefing doc’s FAILED to put on the panel…JUST ONE EXPERT who would’ve or could’ve helped…oh yeah…
I SMELL A DIRTY RAT.
Matt
Industry Insider commenter here is obviously a bashing troll. The writer of the article did not either do their research or they too are trying to get the general thinking on Lorq to be negative. The writer started out to be unbiased but then rolled over to show their true intent of unethical reporting standards.
Investigative reporting means to investigate you bashing punk. Get some ethics and hopefully before then you will find yourself on the losing side of a lawsuit which you do deserve.
Stephen Halstead
I signed the letter, and have a substantial sum invested in ARNA. I listened to the panel hearing, reviewed the comments and concerns from the voting members. The letter is straight forward asking for a non-biased review. The FDA’s actions involving this panel were far below professional, misleading, and showed strong bias laden comments from Dr. Colman. Many are concerned that the FDA secret briefing documents were leaked to the investment community several days prior to the official public release date. The totality of the events surrounding this FDA panel do not pass the smell test. Investors made and lost millions on this panel review. It deserves a new hearing and investigation.
carmen dimartino
I have a friend who works with new drug app’s and she simply stated our FDA could not make an educated decision. She contends that is why drugs are approved in Europe and then we use the rest of the world as our clinical trials population. Now that an effective agency!!!!!!
industry insider
Matt, I don’t have a public voice, but Matthew Herper of Forbes Magazine certainly does so, and he thinks that the drug is going down, which I happen to agree with. The investors seem to agree with both Mr. Herper and I, based on the fact that ARNA’S share price has tumbled from $7.00+ dollars/share to $1.72/share in about one month’s time.
Relevant links are below
http://blogs.forbes.com/matthewherper/2010/10/04/why-the-fda-should-say-no-to-these-drugs/?
partner=yahootix
http://invest.arenapharm.com/stockquote.cfm
industry insider
BTW, there is a formal mechanism, the Citizen Petition (link below) for voicing concerns to the FDA. An “internet petition” as such does not require an Agency response, unlike a Citizen Petition. Practically speaking, even a Citizen Petition at this time would not be practicable since FDA response time to CP’S is usually on the order of months, and the PDUFA date for ARNA is less than three weeks away. Other than being suitable for framing, I see the internet petition as going nowhere at this point.
http://ezinearticles.com/?Submitting-a-Citizen-Petition-to-the-FDA&id=1849253
Tim
For those that want to read this petition and draw their own conclusions visit http://www.petitiononline.com/mod_perl/signed.cgi?passlorc
Rely on your own common sense, not what some analysts may say on their websites, they work for someone other than themselves. Look at the science behind the drug that has been proven by Arena, not the skewed representation we got by the FDA.
-Tim
Goodguy
Thank you Ed Silverman for bringing to light this travesty for the obese population of this country. I also commend Cohor above for bringing to light the issues that real people struggle with on a daily basis.
The FDA Advisory Committee Meeting regarding Lorcaserin on 9/16/2010 conducted by the US HHS FDA was IMHO the absolute worst and most disgraceful example I have ever seen or heard of The Federal Government of the United States in action.
I am embarrassed at my government’s conduct in the eyes of the world in this matter, especially given the massive obesity problem in this country. Wake up people! Healthy food costs more. Obesity is at pandemic proportions,
especially among the poor who cannot afford the healthiest food! Diet and exercise alone is not working for a large portion of the population. They need additional safe remedies.
I understand that seven of the nine AC members stated that their negative votes were due to a.) the inappropriately (according to various MDs) grouped and FDA presented rat data to which b.) there was no qualified toxicologist (human or animal) nor oncologist available on the panel to explain. Perhaps some or all of those seven would have voted Yes if neither a.) nor b.) were the case. This in and of itself calls out for the AC committee meeting conduct to be investigated, and its recommendation to be set aside. A new fully qualified panel should be convened, and the new AC meeting run in a manner beyond reproach.
Both the FDA’s conduct as an agency and that of the governmental employees responsible for the: rat data as presented; choosing a committee with no qualified oncology or toxicology member; and/or apparently intimidating members (regarding their names being associated with a drug that might be recalled; and not being able to abstain from voting) should be investigated by the Office of Research Integrity and House and Senate Oversight Committees, and the Inspector General of the Dept. of HHS, for their conduct during the hearing and subsequently with news outlets.
I encourage you to make your views known to these organizations:
–Office of Research Integrity http://ori.dhhs.gov/about/contact_ori.shtml
–Office os the Inspector general of HHS ….Direct Inquiries to the Office of The Deputy Director for Investigations
http://oig.hhs.gov/contact.asp
Dan K
I am an experienced investor and I invested a lot of money in ARNA after doing extensive due diligence. I believe it when a President says that his drug meets FDA requirements for approval. I also put faith into it when a major international drug company such as Esai pays $50,000,000 as just a down payment to distribute Lorquess from Arena. The fact that the President said it was so and that Esai paid $50,000,000 conviced me that Lorquess met the standards for FDA approval. It is clear to me that the author of the FDA briefing document must have had alterior motives because it perverted the truth. Lorq is a safe drug IMHO.
Bill K
First, I want to note that the issue as to whether a publicly traded pharma is required to disclose to investors all toxicological data, even data that has been reasonably deemed by the pahrma to be without statistical significance, is the principal issue in a case that the Supreme Court will be hearing soon (probably in the spring of 2011). The case is Matrixx Initiatives v. Siracusano. See the following link: http://www.supremecourt.gov/Search.aspx?FileName=/docketfiles/09-1156.htm
If you take the time to obtain and read through the filings in that case, you will see that the drafters of the ARNA petition are clearly not the only ones making the “sweepihg” “dramatic” claim that “releasing all toxicology data from pre-clinical or animal studies may fatally damage equity markets” for pharma companies.
Regarding lorcaserin, I would argue that the FDA - by authorizing human clinical trials and then accepting the NDA based on the data from the huma trials - played a role in lulling ARNA into believeing that the FDA did not consider the rat canacer data of statistical significance (which I am certian it is not). Then, after being led into a dark alley by the FDA, several bureaucrats at the FDA clubbed ARNA over the head at the advisory panel. These bureacrats first “re-discovered” the rat cancer data and improperly manipuilated it to make the breast cancer risk seem more significant than it is. They then put this “alarming” data in the briefing documents for the panel along with some highly biased language about lorcaserin’s marginal efficacy; all in an effort to tip the benefit/risk scales against a drug that up until then was viewed as having a very beinign saftey profile. The bureacrats then established an advisory panel lacking the expertise to assess the FDA bureaucrats’ analysis of the rat cancer data. (Nothing like having a judge who knows nothing about the law.) Then, as a final touch they made highly biased statements at the panel and scared many scientists on the panel to cast a “no” vote out of fear of the unknown.
It was a set up. No doubt about it. The question is: Why? There are several answers to that question, one charitable, most not. The charitable explanation is that the FDA bureaucrats, in their misguided zeal, really wanted to ensure that they kept a drug they (erroneously) view as having an unacceptable or unknown breast cancer risk off the market. But even that explanation still means that, by skewing the data and making biased statements, they did something they should not have and acted both unethically and in a manner that damaged ARNA by depriving it of its legal right to a legitimate and objective assessment of lorcaserinb by the advisory panel.
Frankly, I don’t buy the charitable explanation. The other not-so-charitable explantions as to motive have to do with the influence of Wall Street and Big Pharma at the FDA.
Bill K
Sorry about the typos in the above.
Bill K
I also feel compelled to rebut the assertions of Industry Insider above. A spokesperson for the FDA has said that the vote of an advisory panel is not nearly as important as what is said at the advisory panel. Given that a number of members of the advisory panel clearly voted “no” out of uncertainty about the significance of the rat cancer data, the FDA is most likely to issue a CRL requiring ARNA to conduct more rat trials, not a non-approval letter.
But Industry Insider in his posts here is clearly hoping that we buy his line that ARNA will get a full non-approval letter and that - because of its cash position - will have to go out of business. Apparently, he wants to see the ARNA’s stock price drop even further.
Furthermore, I find it deeply troubling that someone who is looking at ARNA’s cash position also says that he has “worked with and observed Dr. Eric Coleman’s work at FDA over two decades.” Wow. Now what busines would a stock analyst (someone who discusses ARNA’s cash position and the possibility of it going out of business, issues that have nothing to do with the petition or the conduct of the advisory panel) be doing working for two decades with Dr. Colman????
As I said above: “The other not-so-charitable explantions as to motive have to do with the influence of Wall Street and Big Pharma at the FDA.”
industry insider
I’d like to hear from some people on these boards who like me 1) have actually done pharmaceutical research on a diet drug, 2) hold no stock nor have no financial holdings whatsoever in ARNA, and 3) did not sign the “internet petition”. Because these posts are rife with conflicts of interest and buyers’ remorse from ARNA investors, I’d like to hopefully hear from someone, like me who is a scientist in the area on an APPROVED diet drug, has actually worked with the members of the FDA Endocrine/Metabolic Commitee, and has no financial conflicts of interest.
Sorry, Bill K. I’m not an analyst as you can see from above. Oh, and BTW, ARNA does not have to worry about its cash position. It will not have one in light of the the recent individual and shareholder lawsuits based on misleading public statements from the company. Also, cross checking the signatories on the petition with the financial blogs, many of those “concerned citizens” who signed the petition are actually disgruntled shareholders who lost money big time when ARNA’s stock tanked.
industry insider
Bill K, in light of the punishment of former FDA Commissioner Lester Crawford for his stock dealings, do you honestly think that anyone at FDA would be foolish enough to risk their career by talking to a stock analysts?
industry insider
Bill K, just FYI, having been involved with two year ity carcinogenicity studies on diet drugs and other drug classes, it is actually fairly routine for the FDA to wait until the end of the NDA process to deal with the carcinogenicity issue. In the absence of serious animal malignancies, it is actually rare for the FDA to order a clinical hold of an ongoing Phase III trial in these cases. It assumes that the company will do the right thing. If the ARNA executives interpreted the FDA’s “benign neglect” of the carcinogenicity data as meaning that the FDA was ok with it, all that tells me that they ARNA not have sufficient depth of regulatory experienc to know how the FDA actually proceeds in these cases.
If the officers of ARNA had such experience with how the FDA works in these matters they would have known that FDA was NOT necessarily dismissing the animal data, and therefore out of a sense of caution they would have disclosed the animal data in their SEC filings. Thus, they clearly failed to disclose a Material Adverse Event to the SEC; they just “thought” it was not material because of their ignorance of FDA procedures. That position will not save them in court, and it should not save them in the court of public opinion either.
industry insider
BTW, here’s a quote from a financial trading website, showing the style of how these guys actually think and talk. Clearly the interest of patients are not their foremost concern:
“…This will require every FDA officers must be thoroughly investigated and the entire Panel and their contacts must be reviewed with a forensic investigation. The petition on this board will definitely will go all around the world not only scientific world but also all major market media and investment world. Many many mutual funds they have invested in ARNA and many are included in retirement plans. Many local municpal govet. pension plans may have invested in ARNA based of FDA approval of NDA…”
industry insider
Animal Testing 101. From Investors Hub. Read and learn:
http://investorshub.advfn.com/boards/read_msg.aspx?message_id=54495788
USA SOL W FDA
Industry Insider obviously has a substantial short position in ARNA. The FDA never screws up and they cannot be bribed by hedge funds. He’s a professional who makes that clear.
DNDN gave us a reality check on what really happens behind the scenes. We won’t go there though.
USA SOL W FDA
What panel doctor wouldn’t vote no after being scared to sign off on it by the notes and by Colman’s warning about it being on their record for life. Add to that the fact that none of them knew a thing about tumors and cancer and the outcome was predictable.
Predictable outcomes are easy though when you can construct the notes to meet your needs and scare the daylights out of voters through uncertainty and the convenient fact that no specialists were invited to participate.
In the computer industry I believe they refer to that as Garbage In…Garbage Out.
industry insider
That’s correct, USA. I would not only short ARNA but I would also short Eisai. I put just as much blame on them. IMHO, Eaisi was in a desperate situation facing loss of patent protection on Aricept in November, 2010, with further loss of up to 80% of their $2.5 billion sales/year within the next twelve months. They either did insufficient due diligence on lorcaserin or were lulled into the same false sense of security by the FDA’s “benign neglect” of the rodent carcinogenicity data. Add together the loss of royalty payments from ARNA and the LOE of Aricept, and Eisai is in a world of hurt.
industry insider is a TOOL
Industry Insider, you sir are an ignorant tool.
“… all that tells me that they ARNA not have sufficient depth of regulatory experience to know how the FDA actually proceeds in these cases. If the officers of ARNA had such experience with how the FDA works in these matters they would have known that FDA was NOT necessarily dismissing the animal data, and therefore out of a sense of caution they would have disclosed the animal data in their SEC filings.”
If you conducted minimal due diligence about Arena, you would have discovered that Mark Brunswick is a former FDA reviewer and the current head of regulatory affairs. Mr. Brunswick knows how the FDA works inside and out. His regulatory experience is far more significant than your alleged dealings with Dr. Colman. I truly believe that Mr. Brunswick and the rest of the Arena team did everything they were supposed to, but they were clearly blindsided by an openly hostile and biased panel.
Read and learn:
http://www.bioworld.com/servlet/com.accumedia.web.Dispatcher?next=bioWorldHeadlines_article&forceid=48474
industry insider
BTW, for those of you making derogatory comments about “Mr Colman” at FDA, at least get the name correct. It is Dr. Eric Coleman.
Arena Investor
Industry Insider, do your homework before you come to class.
“…all that tells me that they ARNA not have sufficient depth of regulatory experience to know how the FDA actually proceeds in these cases. If the officers of ARNA had such experience with how the FDA works in these matters they would have known that FDA was NOT necessarily dismissing the animal data, and therefore out of a sense of caution they would have disclosed the animal data in their SEC filings.”
If you conducted minimal due diligence about Arena, you would have discovered that Mark Brunswick is a former FDA reviewer and the current head of regulatory affairs at Arena. Mr. Brunswick knows how the FDA works inside and out and is far more knowledgeable than you and your alleged dealings with Dr. Colman. Arena had all the right pieces in place, but they were clearly blindsided by an openly hostile, biased, and shockingly unqualified panel. If Lorqess fails to gain approval, it will not be because of Arena’s lack of regulatory experience as you insinuate in your ill-informed post.
Read and learn:
http://www.allbusiness.com/legal/health-care-law-drug-medical-devices-approval-fdas/12850412-1.html
industry insider
If you want to use the term “blindsided” by the Endo/Met Advisory Committee, that’s fine, but do your homework and you’ll see that past is prologue. Open up the link to the 1996 Meridia Advisory Commitee meeting transcript, and read about Dr. Coleman’s “favorite study”, BPI 855, which was an ABPM study that showed Meridia to significantly raise diurnal BP. Although he acknlowedged that it was a flawed study (and this one that the sponsor didn’t think would hurt them), he nevertheless used it as a basis for recommending against approval on safety grounds.
I agree that it is impossible to know where the blindsided hit is coming from. The difference back them is that we didn’t have hedge fund managers betting the farm on approval, and thus there were fewer individual fortunes to be made. The sponsor wasn’t faced with going out of business based on the outcome. In FY 2010, a negative outcome is far more than just the cost of doing business.
If Mr. Brunswick is as experienced as he is, then he is probably among the least surprised by the actions of Dr. Coleman and the Endo/Met Commitee
http://www.fda.gov/ohrms/dockets/ac/meridia.htm
Michael Murphy CFA
I have reformatted and added to the petition, and sent it by FedEx to the cc list.
http://newworldinvestor.com/open-letter-to-fda-re-arna/
Industry Insider: When you say “Oh, and BTW, ARNA does not have to worry about its cash position. It will not have one in light of the the recent individual and shareholder lawsuits based on misleading public statements from the company,” do you realize ARNA has E&O insurance, and that these suits are common and settled out of court by the insurers paying the plaintiff lawyers?
Arena did not ignore the rat data due to a misguided interpretation of the FDA’s “benign neglect.” They ignored it because fibroid tumors in rats are irrelevant, and cancerous tumors at doses 56X to 84X the human dose are irrelevant. They did not expect the FDA to combine the fibroid and cancerous tumors to force statistical significance at a lower (but still high) level, or to arrange a panel that did not include anyone qualified to judge the meaning of the rat tumor data and analysis, or to say that fibroid tumors are dangerous because the female rats eventually died of them. In short, they did not expect the FDA to blatantly cheat.
Lab_Rat
If Mr. Brunswick was blindsided by the FDA’s response to the carcinogenicity data, perhaps in the future he could hire some rank and file investors to advise him. From the 40% drop in the stock price the day this news was announced, most investors apparently recognized this for what it was as soon as it was announced.
And BTW, I’m not short Arena, nor am I the lackey of some hedge fund that is.
I also refrain from sending petitions to congress that omit any mention of my large financial interests in the subject matter, while pretending to be a group of “concerned citizens”.
industry insider
Thanks for your comment. It’s nice to hear from someone who also saw through the internet petition, which, together with posted letters to Sebelius and Grassley will end up in the circular file. Sebelius has more important matters, such as calling the evil insurance companies on the carpet. It also betrays ignorance of the petitioners. Drug approvals never go above Janet Woodcock’s level. Any letter to Sebelius from “concerned citizens” (aka worried hedge fund managers) will get bounced to Woodcock, who will then redirect it to the circular file.
Lab_Rat
I can just imagine Grassley, who is one of the industry’s biggest critics, getting a “concerned citizen” petition from a bunch of investors who are unhappy their company’s potentially carcinogenic weight loss drug did not get approved. Probably the last person in the world (after Waxman) these guys wanted this issue brought to the attention of.
This whole episode has been unbelievable. Presumably the result of a bunch of biotech-naive investors thinking there was nothing complicated to understand about a weight loss drug. Just another consumer product. Then they don’t understand why they lost their money and get mad.
Sending a letter to Grassley just shows how little they understand the history and dynamics of the industry.
Bill K
Industry Insider: I believe, after having looked again at the FDA website, the spelling is Colman, not Coleman. And from what you have posted, I agree you are not an analyst, rather it seems you work for a competitor of ARNA. And you are looking for comments of from others who are non-conflicted? Does not your position with a competitor mean thta you too are conflicted and would enjoy seeing the demise of ARNA?
Josh
I have to laugh at the “investors” coming on thinking that they are all of a sudden experts in clinical trials and attacking anyone that disagrees with them. A good portion of people that come to this site have some sort of background in medicine/pharmaceuticals and thus probably have a bit more experience with the FDA, advisory committees, clinical trials, and manufacturing than said investors…
Bill K
Josh: What this is about is not just medicine or pharmaceuticals or clinical trials or advirory committees or animal testing. It is just as much about the law, the proper conduct of the regulatory review process, the limits of agency discretion, and the prospect of illicit influence. The subject matter is not the exclusive domain of scientists.
industry insider
Bill, I’m an independent consultant. I’ve spent the past 10 years advising companies on strategic acquisitions and divestitures. Although I work in Business Development and Licensing, none of my companies are in the obesity business. By way of full disclosure, I worked on sibutramine (Meridia), and was actually involved with the conduct of the flawed study, BPI 855 that got Dr. Colman’s attention because of the increase in diurnal BP. It was probably the low point of my career when the Advisory Panel voted down the product. Tht is why I was able to cross-reference Dr. Colman’s presentation from 14 years ago. No way I would have remembered it otherwise.
No, I don’t work for a competitor, but have been on the front lines of the Redux, Meridia and Xenical wars, and have hopefully earned a few Purple Hearts. My own belief is that the long-term weight regain with all of these drugs (following a plateau of weight loss after 1-2 years) has put in the mindset of the FDA that the long-term risks of these drugs outweigh the benefits. This is one reason why many companies have abandoned diet drug programs, which would logically seem to create an opening for a company like Arena. That’s why I can understand why they did their program with lorcaserin.
This is where I see a possibility for lorcaserin. Because of the plateau phenomenon of weight loss, these drugs are basically ineffective after 2 years. If lorcaserin therefore got an approval for short-term (i.e. 2 year) use with a Black Box Warning) it might minimize the carcinogenicity concerns. The rat cancer data would likely get a bold faced warning as well, and Arena would be left with a watered down label.
In my experience, virtually 100% of companies would rather have a weak label than none it all. Cynical to say, but then the Marketing folks could then develop an off-label program to circumvent the weak package insert.
industry insider
Meridia Pulled from US Market:
News just broke. Maybe Dr. Colman was right after all.
http://www.marketwatch.com/story/abbott-yanks-diet-drug-meridia-from-us-market-2010-10-08
industry insider is a TOOL
Industry Insider, after chastising people for misspelling Colman’s name, I am pleased to see you finally corrected your error. However, it makes your alleged dealings with him even more suspect since you didn’t even know the correct spelling of his name until today.
“I’ve worked with and observed Dr. Eric Coleman’s work at FDA over two decades. I disagree with some of his views, but he is very highly respected within the agency, and the petitioners will be hard pressed to overcome his recommendations.”
“BTW, for those of you making derogatory comments about ‘Mr Colman’ at FDA, at least get the name correct. It is Dr. Eric Coleman.”
industry insider
Sorry, I don’t belong to the “Birthers” who care about how someone’s name is spelled on their birth certificate or whether they have an arabic sounding middle name. I have more important things to do, such as lending my scientific and business development expertise to those poor souls on this board who can benefit from both. And since bashing science is a constant on these and other boards, I would offer to the bashers these words of wisdom, to paraphrase Oscar Wilde and Ralph Waldo Emerson (you may not have read them since Western Literature has all been outlawed in today’s Mickey Mouse educational system), as follows: “A foolish consistency is the hobgoblin of little minds and the last refuge of the unimaginative”. Read something other than the 200 day moving average of your favorite stock and using Wikipedia as your encyclopedia and you might become a more well-rounded person.
industry insider
Hey stock picking is more fun, kids, isn’t it? Here’s the latest from the geniuses on the Yahoo Finance message board for ARNA
ARNA WILL BE APPROVED ON OCTOBER 22, IT IS A LOCK!! 46 minutes ago Set fear aside go back to what you know about Lorcaserin, safe and met efficacy “agreed to” FDA end points! It is the safest of all three, FDA will approve then dump vvus and orex back to the drawing board for 2 years.
Go hash out over a few Mojitos or Cosmos or what ever you young and boring do on a Friday night after The Street closes down and you’ve run out of after hours trades and promises to be home for once to your families on a weekend.
industry insider is a TOOL
Industry Insider, you have ZERO credibility.
How can you claim to have “worked with and observed” someone’s work for OVER TWO DECADES but not know how to spell that person’s name? You are (a) an idiot, (b) a liar, or (c) both. I vote for (c).
Run along and spread your misinformation somewhere else you ignorant tool. You have been exposed as a FRAUD.
industry insider is a TOOL
And just so we are crystal clear, it’s spelled C-O-L-M-A-N. Got it?
Psych Resident
Excuse me. IIIAT, it seems to me that you have either Tourette’s Syndrome or some form of Thought Disorder with all of this perseveration about how someone spells or doesn’t their name (perseveration is a clinical term for repeated pronouncements or gesticulations about matters trivial or obscene). I think you should seek professional help, IMHO.
industry insider is a TOOL
Since II refuses to acknowledge that he is full of sh*t, I feel compelled to call him out. And thanks for the diagnosis PR, I am sure you are 100% correct based on analyzing a few random posts on a message board. I will take your advice for what it is worth - nothing.
Steve
Bill,
I’d say that this has degenerated in the same way as pretty much every other blog discussion of Arena that I have witnessed.
Prior to the release of the FDA briefing docs, anyone suggesting that lorcaserin had less than a 101% chance of approval was a “tool” of the hedge funds, or an undisclosed short.
Once the briefing docs came out, anyone who suggested that the cancer seen in rats would be an issue at the AC meeting was a tool of the hedge funds, or an undisclosed short.
After the AC voted to recommend against approval, the FDA suddenly became “corrupt” and the tool of outside financial interests.
You can hopefully see how it is hard for those of us who have watched this discussion over the last few months to take the most recent allegations seriously.
Psych Resident
IIIAT, most good psychiatrists can make a presumptive diagnosis within the first 30 seconds of seeing a new patient. In your case, it was about 30 words. Seek help, please.
No Diet
Interesting to read about a lot of conflicting opinions about how the FDA behave with regards to ARNA.
Based on what we have seen from all the postings, we can very much tell that a lot of people would like to think that the FDA is beyond reproach. Of course, we would like it to be this way, otherwise they (FDA) will be just like any other government organization that is saddled by corruption.
The concern though is that this benevolent role by the FDA is not without blemish. Look at the FDA insider complaint about the alleged corruption that permeates in the organization?
Regardless, we have to put our trust in an organization that has a lot of things to do with our health and well being. This does not mean that we should trust them blindly, but to trust that their obligation to the public with regards to promoting health and safety are the paramount issues. What we have to worry about is a situation when “FDA” staffers use their positions not for the intended good, but as a podium to punish those whom they want to punish for whatever reason by manufacturing doubts where there is none.
So, in the case of ARNA, it is clear that something cynical happened when the “Rat” issue was presented. If ARNA is not telling the truth about their “Rat” research data, then prove them wrong. Where is the problem? Is it the ARNA rat data or the FDA rat manufactured data? I beginning to think that it is the FDA rat data.
Old Timer
I propose that we go back to the old ways of doing things; no Public Advisory Committee Meetings, no published briefing documents for the pseudoscientists on Wall Street to get ahold of and risk their clients fortunes, no public interviews with biotech CEO’s on business radio and TV, hyping their drug. Twenty-five years ago , every piece of information pertaining to an NDA was strictly embargoed from the public until approval. Everything was hashed out behind cclosed doors in smoke-filled rooms between FDA and sponsor, and the no one knew the outcome until the day the decision letter went to the sponsor. The “Pro’s were in the loop and the “Joe’s” were out of it. All deliberations between FDA and sponsor were confidential. Somehow it all worked, and IMHO for the better.
All that the public ever saw was the compamy press release saying yea or nay on approval. There was no FDA electronic publication of the medical reviewer’s summary, etc. Thus there was no disparagement of FDA officials by the pseudoscientist/analyst/”concerned citizen” petitioners since they would not know whom to target.
Steve
No Diet:
This discussion is not based on broad assumptions about the FDA but on the facts of a very specific situation. No one here is as naiive as implied by your note.
The data being debated was all generated by Arena. There is no “FDA data”, only the FDA’s and Arena’s differing interpretation of the data, and what is arguably a third interpretation put forward by a group of investors.
It is obviously important not to naiively see government regulatory agencies as purely benign surrogate parents. But I think it is also important not to assume that the “sophisticated” response is to believe every accusation you hear.
Richard
Sources are indicating that Pfizer is set to purchase Arena Pharmaceuticals. This can really boast both companies especially Arena as they try to get thier obesity drug approved
Sam
I smell a rat posting comments.
His name is “industry insider”
EddieVis
Dear Sam the rat smeller, at least Insider is polite, has a vast experience, has admitted he’s not always been right and is a constructive asset to this pharma blog-website.
Joe Investor
ARNA is now on alert for a buyout at these levels. You can bet that someone BIG is accumulating this stock. (PFE, Roche, LLY, GLX or BMY?)
industry insider
Joe, the ARNA stock is up over 5% today. Would that suggest that the large institutional investors suspect that a buyout is possible? On the other hand, 5% isn’t big considering the recent beat down in share price. Just trying to understand today’s big uptick. No skin in this game.
Joe Investor
I am writing in protest to the recent ruling of Arena’s new weight loss drug.
From everything that I am reading, it seems that the FDA made some very tactical errors, someone leaked their findings and then the results of rats dying from toxic doses of the drug were erroueous in nature. Rats will almost always die or contract cancer with toxic doses.
Here are some facts to get to the bottom of:
28 out of 65 female rats that took the placebo developed mammary adenocarcinoma while 35 out 65 rats that took 5x the normal dose of lorcaserin developed adenocarcinoma. (5 Times - A high dose)
Sprague- Dawley rats which were used in this study are prone to High cancer results.
The Sprague Dawley rat is an outbred multipurpose breed of albino rat used extensively in medical research. Its main advantage is its calmness and ease of handling. This breed of rat was first produced by the Sprague Dawley farms (later to become the Sprague Dawley Animal Company) in Madison, Wisconsin. The breeding facilities were purchased first by Gibco and then by Harlan (now Harlan Sprague Dawley) in January 1980.
Sprague Dawley rats have a High Tumor Incidence rate, period.
Summary
A tumor incidence of 57 per cent was observed in 150 female rats allowed to live out their life-span as normal, control animals on standard laboratory chow. One hundred similar rats on a special fat rich diet developed an 80 per cent tumor incidence.
Ninety-five per cent of the tumors observed involved mammary gland tissue. Twelve per cent of all tumors observed were of a malignant type. Eighty-seven per cent of all tumors appeared after the rats were 540 days of age, and the mean lifespan after a tumor was first observed was 140 days.
More:
Arena turned to pathologist Dr. Gary Williams to explain the rat test results to the FDA panel, which included numerous physicians but none who specialize in oncology??? Why???
Williams said the breast cancer that occurred in some rats was caused by a physiological mechanism UNRELATED to the drug and that other cancers were triggered by the extremely high doses given to the animals.
“It’s a shame there were no carcinogenicity experts on the panel,” Lief said. “My view was that they were having difficulty understanding our presentation.”
Joe
industry insider
Joe, while the ARNA drug met one of the two regulatory benchmarks for efficacy, a placebo-subtracted difference of approximately six pounds in one year is not robust. This is where the rat data enter the picture. With a robest efficacy result, the regulators could down play the rat data. It all boils down to benefit vs risk, whether that risk is real apparent. In the case of locaserin, a real weight loss of only six pounds is not enough to offset FDA’s concerns about the rat tumors, whether real orr appearent.
Also, an argument for an apparently clinically unrelated mechanism of carcinogenicity in the rat tumors is a failed apprach that has been tried many times in the past. I would respectfully suggest that you cut your losses before the stock becomes delisted; then it will be too late.
hamlet
Industry Insider “The lady doth protest too much, methinks” If it smells like a rat, acts like a rat, then Dr. Eric Colman M.D. is the rat… time will tell, as his former boss Dr. David G. Orloff M.D. would attest to, who like Bernie Madoff also got caught… gee.. their names rhyme.. how poetic..
Jim
To Industry Insider
Maybe an online petition will not work but I would bet money that if those same people that siged the petition write their congressional and senators that there will be many questions asked of many people. In fact, this is what all of the people that signed the petition should do if the FDA either disapproves or at the very least fails to convene another A/P meeting with all the correct and appropriate parties represented.
Also the issues with Meridia were in the files at the time of the A/P meeting.
Any drug that the FDA approves can show more side effects the longer it is on the market. So the answer for Dr. Woodcock is that given the best data we had at the time this was our decision.
Why did the FDA let human trials begin if cancer issues were a major concern?
industry insider
Thanks, Jim. D-Day is less than 24 hours away on Lorquess. Heavy short-selling of shares today dropped ARNA share price over 6%. Further price declines post rejection (as many on the Street anticipate) will bring the short covering folks out of the woodwork. I’m sure that the FDA skeptics are thinking that inside decision makers at FDA have already telephoned their brokers within the past 24 hours with the bad news, which therefore must be responsible for the sell off.
As I’ve said before, I have no financial interest in this outcome. My experience tells me that rejection is a virtual certainty. If I’m wrong I’ll have the proverbial egg on my face and you can take your shots.
I look forward to reading the posts from the “concerned citizens”.
industry insider
Here’s the FDA response to investors, via Matthew Herper at Forbes. Proves that there was indeed an adequate toxicology review and suggests that even if the rat data were clean the drug would not have been approved anyway by the Panel.
Hopefully by the end of today we can bury this dog.
http://blogs.forbes.com/matthewherper/2010/10/22/fda-responds-to-outraged-arena-investors/?partner=yahootix
hamlet
Industry Insider, for someone who has no skin in the game or any financial interest in Arena, to post 24 of the 67 total comments on this subject seems a little suspicious and disingenuous. Your need to resort to name calling is certainly uneducated as well as uncalled for. Arena is at the forefront of GPCR technology and this is estimated to be a multibillion dollar class of drugs that are yet to be fully commercialized. I do believe they will do just fine given their pipeline and patents. Please don’t resort to name calling and fortune telling and you will have more credibility. Their CRL was quite mild and the path forward looks quite achievable. Persistence, persistence, persistence… no one ever said it would be easy!
industry insider
Hamleme out, here’s number 25. If you can name me a songle marketed product that has come out of G Protein Coupled Receptor technology or any genomic technology you would be illuminating your audience. I’ve seen all kinds of new drug discover technologies come and go; most of them have gone and went. I give you one prop however; at least you don’t worry about how Eric Colman spells his name.
You’re right; I do post with the financial bloggers. In 30 years in the pharmaceutical industry I’ve made enough money to study financial analytics as a hobby. However, like I said I have no skin in the pharma game.
hamlet
This article was written by David Gilmore, Nov. 2004 American Chemical Society.. 1st paragraph, and goes on to say GPCR’s will remain the hub of future drug development for the foreseeable future of Pharmaceutical industry…
If you had to make a wild guess about
the target of a certain drug, your best
odds are with “G-protein coupled recep-
tor.” Drugs targeting members
of this integral membrane
protein superfamily, which
transmit chemical signals
into a wide array of different
cell types, represent the core of
modern medicine. They account for
the majority of best-selling drugs and
about 40% of all prescription pharmaceuti-
cals on the market. Notable examples include
Eli Lilly’s Zyprexa, Schering-Plough’s Clarinex,
GlaxoSmithKline’s Zantac, and Novartis’s Zelnorm.
30 years in the pharmaceutical industry experience and you don’t even know this, wow.. You need to go back to school and get educated, because you are way out of your league, old timer… Anybody without any skin in the game would not be that subjective as to condemn a company or a technology as you have done, so I don’t believe you. I do hope I have provided some illumination.
industry insider
Lorcaserin now proven unsafe in diabetics as well as non-diabetic obese. Data in from BLOOM-DM trial.
http://www.thestreet.com/_yahoo/story/10915771/1/arena-marginal-obesity-drug-now-unsafe.html?cm_ven=YAHOO&cm_cat=FREE&cm_ite=NA
hamlet
Not powered to analyze valvulopathy data and is not statistically significant anyways. If you add to larger study it is not statistically significant. Good spin though.. I am sure Dr. Colman will put some more spin on it and everyone will go along… Spin.. Spin.. Spin… No one writes about Qnexa, topiramate causing Major Cranial Facial Birth Defects in Babies.. causes birth defects in doses 2X in mice, 6x -34x in rabbits and rats across all species. 1.6 BPM increase in heart rate, 4x higher increase in cognitive impairment, 1 1/2 - 2x higher risk of psychiatric adverse events, statistically significant reduction in bicarbonate levels which causes many other complications, diabetes, neuropathy, low bone density and this is the write up by the FDA, Dr. Mary Roberts. NOPE.. no one wants to write about anything bad about Vivus.
Locaserin by the way was never proven unsafe in any therapeutic doses, just some bad spin about rat cancer that was species specific at doses 82x and not seen in any other animals studied. Peace N Light..