PhillyDan

Don't Expect Amylin to Eat the Obesity Market's Lunch

Ruthanne:
Maybe not the right place for this. Here is an analysis that I did yesterday of the results from Bloom and Blossom vs. Equip and Conquer. In my analysis I focused on the number of people as opposed to percentages since both the Bloom and Blossom studies had more people in their studies. I think the information I uncovered is compelling in that the efficacy between Lorcaserin and Qnexa is not as far apart as some would have you believe.
I state it in this post that I used Completer data rather than ITT-LOCF data.

Detailed analysis of Bloom and Blossom 20-Nov-09 08:58 pm
vs. Equip and Conquer. I just posted this on the Vivus board to educate them on how to do read results and do analysis. I used completer data not ITT-LOCF for the analysis. Very interesting results when you peel back the onion. This was in response to someone who mixed dropout rates for all reasons with dropout rates for adverse side effects:

Here is an education in how to read the data from results.

Discontinued rates are different than drop out rates for adverse side effects. For your information, the Equip study started with 1230 people and at the finish only 680 completed for a dropout rate for all reasons of 45%.

The Conquer study started with 2448 people and 1542 people completed for a dropout rate for all reasons of 38%. But the drop out rate for side effects for the highest dosage was 18%. The mid-level dosage drop out rate for side effects is 12%. The Blossom study had over 4000 people in the study. Bloom had approximately 3100 people in that study.

Go up to the Vivus and Arena websites and read the press releases on the results and then do the math. Basically the completion percentage rates were similar. The FDA will look at drop out rates for side effects and Lorcaserin's drop out rates for side effects are lower than Qnexa. 7% for Blossom vs. 12% and 18% for the Conquer study.

Bloom had 1767 people complete the study vs. Equip's 680.
Blossom had 2419 vs. Conquer's 1542.

Bloom had 66% or 1166 people that lost greater then 5%, 583 people lost greater than 10% and 442 lost greater then 15%.
As you can see 583 people is more than 439 people and 442 people is more than 301 (see Equip below).

Blossom had 63.2% or 1529 people that lost greater than 5%, 868 people lost greater than 10% and 604 lost 16.3%.
As you can also see, 868 people is very close to 978. The same for 604 vs. 634. (See Conquer below).

Equip had 439 people greater than 7% or 65% of completers, and 301 lost greater than or equal to 14.7% or 44% of completers.
Conquer had 978 greater than or equal to 10% and 634 greater than or equal to 13.2% of the completers.

As you can see, that a significant number of people (2,695 for Bloom/Blossom combined lost greater than 5% of body weight), that is much greater than the number of people who completed the Equip/Conquer studies (1417 combined who lost greater than 5% of body weight) lost a significant amount of weight in both Bloom and Blossom. Certainly Qnexa showed better efficacy numbers but averaged over a smaller number of people. In addition, the phaseIII studies were totally designed differently than each other. Lorcaserin for safety and Qnexa for efficacy.

The bottom line is that the Lorcaserin's efficacy numbers are very good when you do the detailed analysis. Way good enough for FDA approval on top of it's excellent safety profile. The facts are that Qnexa's safety profile is in question. You might not like hearing that but that is the facts.

All numbers are for completer data or per protocol not ITT-LOCF that the FDA will use but do the analysis and the same results will be shown.

I know the issue of placebo adjusted weight loss comes into play but I question why the weight loss of the placebo patients in the Qnexa studies was not much higher? Particularly when the Qnexa studies had a stricter diet. Something to think about and the reason why the FDA has "either/or" guidelines.

Disclosure: Long Arna, had a position in Vivus but sold after phase III results for Qnexa were announced.


On Nov 03 09:44 AM Ruthanne Williams Roussel wrote:

> Hi PhillyDan, thanks for your comments, which are always welcome.
> There are two Phase II studies on the pramlintide/metreleptin combination.
> The first is the one with 177 subjects, and was a Phase IIa proof
> of concept study published here www.pnas.org/ in 2008 (search
> the archives on "pramlintide"). The second study is the Phase IIb
> study with results announced July 2009, which enrolled 600+ patients.
> I don't think this changes your point though.
>
> I guess one reason I am less concerned about side effects of Qnexa
> and Contrave than you are (I know we have talked about this before)
> is that these are tolerability concerns rather than safety concerns.
> How uncomfortable are these effects, how long do they last, and are
> people willing to put up with them for a potential weight loss benefit?
> We already know that they weren't barriers to approval for the monotherapy
> component drugs for other indications.

Don't Expect Amylin to Eat the Obesity Market's Lunch

Thanks for the correction. I did reread the press release and saw my mistake. That is the problem sometimes on relying on memory.

I am less concerned about the Contrave side effects except for a very few cases of patients in the study developing kidney stones.
Qnexa in my opinion is a different story in that they have so many side effects and to your point, most of them are tolerability issues. What concerns me is the Tingling and Dry Mouth side effects which are both greater than 5% over placebo should not be brushed away so lightly by the FDA. I also have researched the exclusion list for both Phentermine and Topamax and the list is a long one. My other concern that has never been fully satisfied by Vivus is how with the combination of these two drugs that the side effects are less than with each drug separately. It does not make sense to me nor do their explanations hold water.

I understand they have a proprietary drug delivery system added to the combination and that may account for some reduction in the side effects but not to the extent shown. Topamax alone has some serious side effects. I certainly understand that people taking Topamax have serious conditions and the benefit to risk ratio may be worth it for those patients, but for weight loss, I don't believe you take that risk for the benefit of weight loss.

On another note, I would like to see Arena publish the survey results of the MD's they surveyed at the Obesity Conference.


On Nov 03 09:44 AM Ruthanne Williams Roussel wrote:

> Hi PhillyDan, thanks for your comments, which are always welcome.
> There are two Phase II studies on the pramlintide/metreleptin combination.
> The first is the one with 177 subjects, and was a Phase IIa proof
> of concept study published here www.pnas.org/ in 2008 (search
> the archives on "pramlintide"). The second study is the Phase IIb
> study with results announced July 2009, which enrolled 600+ patients.
> I don't think this changes your point though.
>
> I guess one reason I am less concerned about side effects of Qnexa
> and Contrave than you are (I know we have talked about this before)
> is that these are tolerability concerns rather than safety concerns.
> How uncomfortable are these effects, how long do they last, and are
> people willing to put up with them for a potential weight loss benefit?
> We already know that they weren't barriers to approval for the monotherapy
> component drugs for other indications.

Obamacare: Affordable Private Insurance Is Already Available

Mark: Maybe healthcare is affordable for those that have incomes of over $100K. But for the millions of people that live below or near the poverty level, the amounts you quoted are expensive. I have Polycystic Kidney Disease and cannot get health insurance. I have Medicare and thank god for that so-called Socialist program that CLH would probably want to abolish along with Social Security, Veteran's Hospitals, etc. in favor of giving the wealthy even more tax breaks. I digress. Here again, there are several million people like me that have chronic illnesses that would be denied insurance or pay 4 to 5x the numbers you quoted above.

I also hate the term "Obamacare" it should be called "AmericaCare" since most Americans are in favor of healthcare and Insurance reform. No pre-existing conditions, no recissions, no Health Insurance CEO making $50M a year (for doing what), more competition within states for health insurance plans.

If Health Insurance companies were smart, they would have dropped pre-existing conditions and recissions, develop an entry level coverage plan with higher deductibles for Doctor visits and tests but full coverage for hospitalization. They could have worked with the Government to set up a jointly funded program to defray their costs of covering someone like myself with a chronic illness - a catastrophic fund that is underwritten by the U.S. Government. For people with chronic illnesses that have a good income they would pay a higher premium for their plans or for Medicare but not 4 or 5 times as much. People with lower income levels would have a portion of their costs subsidized by the fund.

If the Insurance companies would have taken these steps five, ten years ago, we probably would not be having this discussion right now. They knew this was coming, but instead of being part of the solution, they spent their time, energy and money on trying to stop it. Well now, they don't get a vote!!

Obamacare: Affordable Private Insurance Is Already Available

You sir are the retarded one! Report me for abuse, but I would challenge you to a duel if they were still legal. I resented when people called Bush the same thing. You may not like him but have respect for the President.
Furthermore he is not a Socialist. You don't know anything about Socialism and probably think it is Communism. It is Super Capitalism that got us into the financial mess in the first place. We are a country that is a mix of capitalism and socialism and that is what is needed to keep the wealthy from taking over. For the people who gave you a plus, they also should be ashamed of themselves.

Maybe you are a Nazis? See how easy it is to put labels on people when you don't have any proof, or hide behind the cyber net. I might also label you a racist? My point is don't call people names or label them when you don't have any proof that would stand up in court of law.


On Nov 09 08:32 AM CLH wrote:

> Its a fact that American health care is the best in the world. No
> one goes to Canada or England for an operation. It may be slightly
> more costly but our care is worth it.
>
> Obama is a retarded socialist. There is nothing that the govt. can
> do better than private enterprise.

Don't Expect Amylin to Eat the Obesity Market's Lunch

Remember, if my memory serves me correct. Amylin's phase II study had only 128 people in it. More importantly, I agree that a lot of overweight/obese people won't be keen on taking an injectable medication. To me this bodes very well for Arna who will file their NDA in December. In addition, Lorcaserin offers good weight loss but more importantly is safe and tolerable and is a novel, well-patented drug. My concern about Qnexa and Contrave is they both have shown more adverse side effects, particularly Qnexa and because of that, I think they will have a more difficult time gaining FDA approval.

I would speculate that in the next few months, we will see partnership action with one or all three of the companies.
Two out of the three in my opinion, based on the Amylin deal stand to get even more lucrative deals based on the fact that all the development has been done and a year from now, one, two or three will have or be close to FDA approval.

Columbus Day Dash and Slash: DepoMed, Vivus, Oncolytics and RadNet

The real questions on Vivus that need to be asked about Qnexa are as follows:

1. Why would a "Big Pharma" buy Vivus for Qnexa, a combo drug made up of two generic drugs (Phentermine and Topamax) already on the market? Yes, they have a slow release formulation but is that enough value added for a "Big Pharma" to spend over a billion dollars to buy Vivus?

2. The safety and tolerability profile of Qnexa is very suspect. Seventeen out of Eighteen adverse effects were greater than placebo in their recent Phase III study results. In addition, they had a 19% dropout rate of patients in the study. Despite the "PR" spin from Vivus, I think the safety and tolerability profile put Qnexa at risk of not being approved by the FDA or certainly having an extensive delay in the review process. Would a "Big Pharma" make a buyout offer with those risks on the table?

Anyone expecting a buyout in the near future will be disappointed in my opinion. A buyout may happen but not until the above questions and issues have been thoroughly addressed.

Why Orexigen's Empatic News Is Good

How many people were in this study? Not many is the answer. Until a full phase III study is done with well over 4000 people in it and heart testing is done, I won't be impressed. Arena with Lorcaserin has the safest effective drug candidate. NDA will be filed in early December and the FDA will approve it in October 2010. They have had over 7000+ patients in the Bloom and Blossom studies. Three years of testing for heart valve issues, a small number of AE's (A lot less than their competitors) and in most cases less than Placebo. The FDA wants a safe effective weight loss drug. Efficacy with a ton of AE's will not do the trick or studies with strict diets and exercise - did the diet and exercise lose the weight or the drug? Weight loss is not a speed game. You want weight loss to happen that a reasonable rate with few or no side effects and just as important, you want the weight to stay off.

Investing in the Obesity Drug Basket

My calculation was based on 52 weeks but Goodguy is correct, the study was 56 weeks long.


On Sep 30 12:38 PM PhillyDan wrote:

> Your Doctor will not agree with that! He will want you to have the
> safest drug that gives you reasonable weight loss while improving
> your diabetes condition and that would be Lorcaserin not Qnexa.<br/>
>
> Remember, Vivus had a 500 calorie deficit per day diet for their
> patients in the study. That equates to 182,500 calories less per
> year assuming followed correctly by the patients. In general a 500
> calorie deficit per day will lead to a one pound loss per week.
>
>
> Riddle me this? Was it the drug or the diet that caused the weight
> loss?

Investing in the Obesity Drug Basket

The only joke is you Penn Bioinvestor. You sir are a liar!!
Murphy never said DNDN would go to $360.00 very soon but his projection was over a number of years. This lie on your part alone does not entitled you to any credibility at all.

Lorcaserin is slated to cost about a $1.50 per dose. Here again, you lie when you say it would cost: "Tens of thousands of dollars".
The average weight loss for completers is 18.2 pounds, the only mistake that Murphy made in his chart above since he uses ITT-LOCF data for Arena but Completer data for Vivus. Over 26% lost greater than 30 pounds. Now tell me that wouldn't make a difference in someone's health? In addition, Vivus had a 500 calorie deficit per day which equates to about a one pound loss per week. I suggest you study the AEs for Qnexa and exclusions and restrictions before recommending a potentially unsafe toxic drug for people.

In closing, you are liar since you have distorted the facts several times in your comments. We don't need liars like you in Seeking Alpha.

Come back when you can get your facts straight.
On Sep 22 08:18 PM Penn Bioinvestor wrote:

> This Micheal Murphy guy is a joke. He kept pumping the stocks he
> own. He predicted early this year DNDN will go to $360/share very
> soon, which translate into about 40 billion market capital for this
> small biotech. (Shocked)
>
> I just asked him yesterday if he will allow me to sell all my DNDN
> shares to him at $180/share, so he can make handsomely 2X on it.
>
>
> I also challenged his pumping on ARNA: Safe? If doctors are looking
> for a low-risk solution, they might be better off prescribing diet
> and exercise changes than trying to eke out an additional 6- to 8-pound
> loss for a 200-pound person on lorcaserin (ARNA drug). LOL.
>
> Put in this way, if a 200 pound person take ARNA's "wonderful' drug,
> by paying tens of thousands of dollars in two years, he shed off
> 4-6 pounds! Toxicology 101: EVERY DRUG IS TOXIC. why not take some
> diet, which is much safer. Game pretty much is over for ARNA, period.
>
>
> I was shocked by his statement ARNA drug can be marketed together
> with Phen. Lack of basic drug approval knowledge: FDA will NEVER
> allow any such drug without all proper clinical trials.

Investing in the Obesity Drug Basket

Your Doctor will not agree with that! He will want you to have the safest drug that gives you reasonable weight loss while improving your diabetes condition and that would be Lorcaserin not Qnexa.

Remember, Vivus had a 500 calorie deficit per day diet for their patients in the study. That equates to 182,500 calories less per year assuming followed correctly by the patients. In general a 500 calorie deficit per day will lead to a one pound loss per week.

Riddle me this? Was it the drug or the diet that caused the weight loss?


On Sep 21 07:48 AM rob134 wrote:

> I am amazed at the author's ability to ignore the phase III data
> on all of these drugs and come to a conclusion favorable to his long
> holdings. If the doctor gives me a choice as to which drug I wish
> to take it will be the one that can provide the most weight loss
> while positively effecting my diabetes. Qnexa wins hands down.

Arena’s Lorcaserin Has Safety Edge

Jocular: Why would any big Pharma want to partner with either Vivus or Orexigen? Both are combo drugs of already existing drugs on the market. I know they have patents but their patents are very weak. I know Qnexa has a slow release mechanism but slow release mechanism's can be added to topamax and phentermine. There is no value-added or really strong patent protection for a big Pharma to bet a lot of money on Vivus or Orexigen. Recommend you read the FDA guidelines about a 100 times so that you finally get it that Lorcaserin meets the recommended FDA guidelines. In addition you will find in the document that they value safety first and efficacy second. Suggest you look at the AE's as the Zacks' article has clearly pointed out and also look at the dropout rate. I know the FDA will!!

Cramer Likes Orexigen: Should You?

Cramer or a member of his staff did a poor job of research on Orex. Particularly regarding when they will file their NDA. All the indications from Orexigen is that the NDA will be filed sometime in the first quarter of 2010.

Arena will file their NDA for Lorcaserin in December.
Vivus will file their NDA for Qnexa in December or early 1st quarter 2010.

He also brushed over the potential safety issues/side effects that did show up in the Phase III study results for Contrave.

Today, JPM Securities initiated coverage for both Vivus and Arena.

The analyst for JPM - Mr. Duncan wrote his analysis for Arena and expressed his concerns for the safety of Lorcaserin. Poor analysis or poor reading skills on his part. The Bloom Phase III study results showed clearly no safety or tolerability issues with Lorcaserin. There were no "Valvulopathy" issues and in fact they were less than placebo. Each patient in the study started with a baseline Echo Cardiogram and received one every three months during the 24 month study. I would recommend he go back and look at the data once again with his reading glasses on!

Arena is set to announce their Blossom Phase III study results before the end of September and Vivus will announce their Phase III study results for their Equip and Conquer studies before the end of September but should announce those results prior to Arena.

The Vivus message board on Yahoo, is getting very antsy about "where are the results". Some posters believe they have the results already which is not the case. They are still going through the "unblinding" process. Patience is a virtue.

The SEC proposes a revised uptick rule that would be easier to monitor, as it disregards the sequence of bids, and has reopened public comment.

Not too late. Need more details but at first look, I like it.

Arena: Obesity Is a Large Market Opportunity

I would like to correct one inaccurate statement in the article. Vivus plans to file an NDA for Qnexa in December 2009 not the middle of 2010. Their Sequel study which is an extension of their Conquer PIII study is slated to be completed by July 2010 with results in November 2010. This 1000 patient study (patients will be rolled over from the Conquer study) is intended to give Qnexa two years of safety data and in addition, will see how well patients do in additional weight loss or maintaining weight loss with Qnexa. This data is not needed for filing their NDA, since per FDA guidelines, they only have to supply one year of safety data. Thus, their should be no impact on filing NDA or FDA approval other than the potential delays mentioned in your article.

Too Late to Board the Biotech Bandwagon?

Well written article with good recommendations for investors. I believe that the Biotech sector is poised for explosive growth and like "alternative energy" promises to be one of the driving forces in the future economic growth of the United States.