Chaz Bono Gives Weight Loss Drugs Celebrity Appeal — Arena Pharmaceuticals Inc. (NASDAQ:ARNA) and VIVUS Inc. (NASDAQ:VVUS)

http://marketplayground.com/2013/07/19/chaz-bono-gives-weight-loss-drugs-celebrity-appeal-arena-pharmaceuticals-inc-nasdaqarna-and-vivus-inc-nasdaqvvus/

Insider Sales at Vivus: Sign of Things to Come?

http://beta.fool.com/beatlesforever/2012/07/04/insider-sales-vivus-sign-things-come/6605/?source=eogyholnk0000001

See disclaimers in the side bar.

Disclosure:  I have no position in VVUS.

thestreet.com is bearish on ARNA--again

Adam Feuerstein, thestreet.com's biotech analyst is once again bearish on shares of Arena Pharmaceuticals. He was also bearish on shares of DNDN and HGSI before they appreciated more than 10-fold from their lows. And he was bullish on VVUS before the advisory committee rejected anti-obesity drug Qnexa, tanking shares more than 60% the next day.

http://www.thestreet.com/story/10829837/arena-pharma-deja-vu-danger.html

In other words, his track record for predicting winners and losers is spotty at best.

Meanwhile, the editors of the New England Journal of Medicine and the Formulary journal, the most respected peer-reviewed medical journal and peer-reviewed drug management journal, respectively, were overwhelmingly positive of ARNA's Lorcaserin benefits for obese and morbidly overweight patients, balanced against a clean safety profile.

Mr. Feuerstein is a "Senior Columnist" specializing in biotech and works for thestreet.com, a public company being investigated by the SEC for accounting irregularities.

http://www.zerohedge.com/article/jim-cramers-thestreet-being-investigated-sec

thestreet.com is also a defendant in a lawsuit seeking $250 million in damages for business defamation, product disparagement, and injurious falsehood.

http://wallstreetpit.com/22485-generex-gnbt-launches-250mln-lawsuit-against-thestreet-com-tsmc

For what it's worth, Mr. Feuerstein has a bachelor's degree in political science from Emory University.

See disclaimers in the side bar.

Disclosure: long shares of ARNA.

ARNA shares gain on VVUS' Qnexa rejection

http://www.businessweek.com/ap/financialnews/D9H09AV80.htm

As usual, some analysts really don't get it.

Separately, Barclay Capital analyst Dr. Jim Birchenough maintained a more conservative "Equal Weight" rating on Arena, saying the FDA seems to have a high hurdle for new obesity drugs and lorcaserin could face its own issues with regulators. Those issues could include adequacy of weight loss and heart valve risks.

According to the recently released New England Journal of Medicine article on Lorcaserin:

http://content.nejm.org/cgi/content/short/363/3/245

Serial echocardiography was used to identify patients in whom valvulopathy (as defined by the Food and Drug Administration) developed.

Among 2472 patients evaluated at 1 year and 1127 evaluated at 2 years, the rate of cardiac valvulopathy was not increased with the use of lorcaserin.

Pregnancy, VVUS and ARNA

This post came from an ARNA message board.

First of all there will never be any human pregnancy prospective studies done. All proven teratogens are known from retrospective studies or case control studies or studies done on animals. This is true of any drug brought to market.

To prove that an agent is a teratogen one might show:


•It is more often associated with individuals having a specific defect than with appropriately matched controls.
•A specific malformation or group of malformations is consistently associated with exposure to the teratogen.
•Biologic plausibility; the agent was present at the time in organogenesis when the anomaly would have to occur. As an example, it is unlikely that exposure to drug X in the third trimester would cause a cleft palate because the palate closes in the first trimester.
•The anomaly was less common before the presumptive teratogen was introduced. Phocomelia (missing upper parts of arms or legs), as an example, was almost nonexistent before the introduction of thalidomide.
•Experimental animals will develop the anomaly if given the presumed teratogen at the appropriate stage of organogenesis.

The BIG difference is that VVUS had a known teratogen!!!.
Using your logic no drug would ever be approved for lack of pregnancy studies.

Daniel
UCLA MD

ARNA analysts

Let's break down who got it right and who got it wrong on VVUS and ARNA.

http://www.streetinsider.com/Trader+Talk/Arena+Pharmaceuticals+%28ARNA%29%3A+Upgraded+to+Overweight+at+J.P.+Morgan/5811273.html

Thumbs up to Cowen & Co. and Piper Jaffray for getting it right, and understanding the importance of safety in FDA approval decisions.

Thumbs down to JPMorgan and Adam Feuerstein of thestreet.com for getting it completely wrong. At least JPMorgan and Adam are smart enough to reverse course on ARNA--after Qnexa's rejection.

Big thumbs down to Rodman & Renshaw analyst Elmer Piros for downgrading ARNA with a price target of $1.

Recall Jonathan Aschoff, a Brean Murray Carret & Co. analyst, at one time had a sell rating on DNDN with a $1.50 price target. DNDN shares recently had a high of over $58.

Is Wall Street crooked? You decide.

FDA panel rejects VVUS' Qnexa, citing safety worries

http://blogs.wsj.com/health/2010/07/15/fda-panel-rejects-vivuss-qnexa-citing-safety-worries/?mod=yahoo_hs

Vivus’s Qnexa, the first of three new anti-obesity drugs under FDA review this year, came before one of the agency’s advisory committees today — and it was a swing and a miss. The panel recommended against approval, with 10 panel members voting against it and 6 in favor, as the WSJ reports.

Trading in the company’s shares was halted at $12.38. But shares in Arena, which makes one of the other experimental drugs, lorcaserin, were up more than 9% in after hours trading, to $4.30. Shares in Orexigen, which makes the other drug, Contrave, fell 10% in after-hours trading, to $4.50. Contrave is similar to Qnexa in that it, too, is a combination of existing drugs.

The problem wasn’t Qnexa’s effectiveness. But panel members said that safety concerns, such as birth defects, depression, and a high heart rate experienced by some study participants, were worrisome in light of the fact that the drug might be taken by millions of otherwise healthy people over many years. They wanted longer-term data than the company had available in order to assuage safety concerns.

Advisory committee votes 10 - 6 No on Qnexa

As I expected, the independent advisory committee voted 10 - 6 (one panel member later changed his vote) against Qnexa being recommended for FDA approval. Shares in VVUS were halted this morning, but when trading resumes, the shares will plummet.

Shares of ARNA, a competitor to VVUS in the anti-obesity sector, gapped up 34% to a high of $5.72 in anticipation of the vote. After the Qnexa outcome, ARNA shares dropped in sympathy below $4, down approximately 10% for the day. However, upon further inspection, lack of sufficient safety data doomed Qnexa, but ARNA's Lorcaserin has a strong safety profile. Hence, I believe shares of ARNA will rebound leading up to its September 16 advisory committee review.

Edit: as I posted this, ARNA shares are recovering close to their previous close above $4 in after-hours trading. All that volatility, and ARNA ended up its round trip near yesterday's close. What a wild day of trading!

Wall Street was bullish on Qnexa's efficacy, but once again, safety ruled.

See disclaimers on the side bar.

Disclosure: no position in VVUS (and glad). Long ARNA shares.

Topiramate not recommended for treatment of obesity

http://www.apmhealtheurope.com/story.php?mots=TOPIRAMATE&searchScope=1&searchType=0&numero=L7098

Topiramate is one of two generic compounds in Qnexa, the other being phentermine. Qnexa is being reviewed by an independent advisory committee today, and will receive full review by the FDA on October 28. Draw your own conclusions.

Disclosure: no position in VVUS.

More excerpts from FDA briefing document on Qnexa

"When assessed as a group, the incidence of cognitive-related adverse events was 1.7%, 2.0%, 5.6%, and 7.8% in the placebo, low-dose, mid-dose, and high-dose PHEN/TPM groups, respectively. The most common adverse event related to cognitive dysfunction was disturbance in attention."

"Approximately 30% of individuals treated with high-dose PHEN/TPM experienced a
serum bicarbonate <21 mEq/L compared to 5.9% of individuals treated with placebo."

"A higher proportion of PHEN/TPM-treated individuals experienced a categorical
increase in heart rate compared to placebo treated individuals (>20 bpm: 19.6% high-dose PHEN/TPM versus 11.9% placebo)."

"Six individuals in the placebo group (atypical angina, coronary artery disease, left main coronary disease) and five individuals in the PHEN/TPM group experienced a non-fatal serious adverse event related to cardiac ischemia defined within this subclass. An additional placebo-treated individual died of cardiorespiratory arrest. Coronary artery disease was the most common adverse event within the placebo group and myocardial infarction was the most common adverse event within the PHEN/TPM-treated group."

"The incidence of depression-related adverse events in the PHEN/TPM clinical trials was 3.4% in the placebo group, 5.0% in the low-dose PHEN/TPM group, 3.8% in the mid-dose PHEN/TPM group, and 7.7% in the high-dose PHEN/TPM group."

These adverse side effects are problematic for Qnexa, in my opinion. We should find out more in today's independent advisory committee review, and the October 28 PDUFA event.

VVUS shares increase on Qnexa efficacy, despite safety concerns

Shares of Arena Pharmaceuticals and Orexigen also rise in sympathy with Vivus. Briefing documents for Qnexa's upcoming review by an independent advisory committee this Thursday (July 15) revealed Qnexa's efficacy for weight loss, but also expressed concerns regarding adverse side effects. The FDA has assigned a PDUFA date of October 28, 2010, for review of Qnexa's NDA.

http://finance.yahoo.com/news/Vivus-weight-loss-drug-faces-apf-1308428575.html?x=0&.v=2

See disclaimers on the side bar.

Disclosure: long ARNA shares.

More risk factors in VVUS' 10-Q on Qnexa

http://yahoo.brand.edgar-online.com/displayfilinginfo.aspx?FilingID=7238278-301188-514052&type=sect&dcn=0001104659-10-026546

In addition, the placebo rate in larger studies may be higher than
expected.

Although we believe Qnexa affects the two major causes of overeating, excessive hunger and the inability to feel satisfied, we may not be correct in our assessment of the
impact the combination of these two ingredients may have on weight loss or their mechanism of action.

In general, significant adverse events and side effects observed in pre-clinical, clinical and post-marketing studies are included in the full prescribing information or label for each drug. The label for TOPAMAX contains reports of side effects, warnings and precautions including metabolic acidosis, acute myopia and secondary angle closure glaucoma, decreased sweating and hyperthermia, cognitive-related dysfunction, psychiatric and behavioral disturbances including one completed suicide in a patient during a bipolar trial, somnolence and fatigue, sudden unexplained death in epileptics, kidney stones, paresthesia and various drug interactions. The label for ADIPEX, a popular branded form of phentermine, contains warnings and precautions including recommendation against coadministration of phentermine with other drugs for weight loss. Adverse side effects include, among other things, pulmonary hypertension, valvular heart disease, drug abuse and dependence, overstimulation, restlessness, dizziness, insomnia, euphoria, dysphoria, tremor, headache, dryness of the mouth, diarrhea, constipation, impotence and changes in libido.

In addition, if the FDA does not approve the full-dose of Qnexa, there is no assurance that they would approve the mid-dose or any other dose of Qnexa.

If we are required to complete a long-term cardiovascular safety outcomes study for Qnexa, the ultimate approval may be delayed for several years and the overall cost of the program will significantly increase.

In June 2007, an FDA advisory panel recommended against approval of rimonabant, an oral obesity treatment targeting the CB1 receptor system being developed by another company. Rimonabant was a centrally acting drug that reduces patients’ desire to eat. The advisory panel expressed concerns about the impact of the drug on depressed patients and also expressed concerns about patients having thoughts about suicide. In addition, concerns about rimonabant’s mechanism of action and interference with the CB1 receptor pathway were also voiced. The company withdrew its NDA for rimonabant shortly after the advisory panel meeting. Although the active ingredients in Qnexa have been previously
approved by FDA at higher doses for other indications, it is a centrally acting drug that may increase the risk of psychiatric side effects such as depression and/or suicidal ideation.

Does VVUS even understand Qnexa's mechanism of action?

Reading all the risk factors for Qnexa in their 10-Q is like watching a horror movie. VVUS has no marketing partner, and no manufacturing facilities. No way it gets approved in October, in my opinion.

See disclaimers in the side bar.

Disclosure: no position in VVUS.

VVUS's Qnexa advisory committee

Qnexa has an advisory committee review July 15, but the FDA's documents will be available July 13. I have many reservations on Qnexa's approvability, including censorship of titration drop out data, the high discontinuation rates, adverse side effect profile, among others. But this one could also be discomforting to VVUS investors:

VVUS's latest 10-Q :
"The number of patients on the low-dose in OB-302 or the mid-dose in the OB-303 study may not be sufficient for approval."

With drugs facing increasing scrutiny regarding safety from the FDA, Qnexa faces some head winds in the regulatory process, in my opinion. We'll find out soon enough later this week.

See disclaimers on the side bar.

Disclosure: no position in VVUS.

Accumulation phase for ARNA over?

Shares of Arena Pharmaceuticals surged today, after consolidating below $4.50 for several weeks, as the shorts and market makers ran the stops. Nervous Nellies are out of the trade--only the strong hands remain, including large institutional holdings by Deerfield Capital, Federated Investors, and Wellington Management, all reknown for being savvy, long-term value holders. Recent investments by Barclays and Winslow Management boost an already strong roster of institutional ownership. Couple that with recent insider purchases by six of eight members of the Board of Directors, and it was just a matter of time before shares of ARNA spiked up in anticipation of announcement of Blossom results, the second of two pivotal Phase III clinical trials for Lorcaserin, the weight management drug with blockbuster potential.

ARNA CEO Jack Lief has indicated that Blossom top-line results will be announced by "the end of September". Short-term traders may want to accumulate tradeable shares in anticipation of the run-up as we approach said announcement, and sell before the news in a low-risk trade. Long-term investors like myself, however, have been slowly accumulating core holdings with an exit strategy post-pivotal events, including Blossom results in September, New Drug Application submission in December, and potential PDUFA in October, 2010. Because Lorcaserin's potential is enormous (some analysts forecast a $10 billion market annually), I will retain a long-term core holding.

This ameliorates the possibility of an announcement of a marketing partnership with a big pharmaceutical company, which would also cause the shares of ARNA to spike up. Traders in and out of ARNA may miss the train. A partnership seems likely, based on previous clinical trial data on Lorcaserin. Safety and efficacy point towards FDA approvability, as Lorcaserin selectively stimulates the 5-HT2C seratonin receptor, a G protein coupled receptor (GPCR) located in the hypothalamus. Stimulation of this GPCR is associated with feeding behavior and satiety.

Most importantly, Lorcaserin's specificity to the 5-HT2C receptor means it doesn't stimulate the other subtypes, 5-HT2A and 5-HT2B. These other subtypes are linked to cardiac valvulopathy, which caused the massive recall of phen-fen, for which Wyeth has paid out $21 billion in a class action lawsuit. Hence, Lorcaserin is both efficacious AND safe.

The weight management sector is wide open, littered with previous failures by big pharmaceutical companies, and a few marginally effective treatments with adverse side effects, some potentially serious. With the safest treatment in the market, and first-mover status relative to their two competitors: OREX's Contrave and VVUS' Qnexa--both generic compounds with a large exclusion criteria and label warnings, ARNA's Lorcaserin has the biggest commercialization potential.

Disclosure: Long ARNA shares.