Vivus: Obesity Experimental Drug Has Promising Outlook

Obesity is reaching epidemic proportions. In some parts of the U.S., more than 30% of the population is obese.

Obesity contributes to rising health care costs because of other conditions that go along with it. For instance, obesity is a risk factor for various metabolic syndromes, which can lead to cardiovascular disease and diabetes.

Treatments for obesity have developed along several lines, encompassing diet, exercise, and surgical options such as gastric bypass procedures, as well as pharmaceuticals. Although there are several FDA-approved agents for treating obesity, many obese patients don't use them because they have side effects, including high blood pressure and flatulence.

The three most advanced treatments in late stage human clinical development are Qnexa from Vivus (VVUS), Contrave from Orexigen (OREX) and Lorcaserin from Arena (ARNA). Qnexa is a combination of two existing drugs, phentermine and topiramate (marketed for epilepsy and migraine as Topamax). Contrave is a combination of bupropion (marketed as Wellbutrin) and naltrexone (indicated for alcohol and certain drug addictions). Lorcaserin is a new chemical entity. Both VVUS and OREX are expected to release their top-line new phase III data in summer, 2009.

Based on research reports by multiple sources like Zacks.com and J.P. Morgan, Qnexa was viewed as the drug with the best profile among all three obesity candidate under development today. Phase III data released by the company from the 6-month supportive Phase 3 EQUATE trial comparing Qnexa to its individual generic components (phentermine and topiramate) and placebo in 756 patients enrolled at 35 centers demonstrated the drug to be both highly efficacious and well tolerated. Patients treated with Qnexa had weight loss of 9.2% and 8.5% on the full-dose and mid-dose of Qnexa as compared to weight loss of 1.7% in the placebo group (p<0.001). Patients on the full commercial dose of Qnexa lost a placebo-adjusted 16.5 lbs, or 7.5% of their body weight, after only 28 weeks of treatment. In my opinion, the study confirmed the robust weight loss effects of Qnexa, was reassuring from a tolerability standpoint, established the legitimacy of the company’s proprietary once-daily pill, and perhaps more importantly, unveiled mid-dose Qnexa as a potentially attractive therapeutic alternative.

Qnexa has not only demonstrated arguably the most potent weight loss properties among late-stage obesity agents, but it’s also the first to generate promising data in diabetics. Qnexa is generating a substantial amount of compelling evidence supporting the drug’s beneficial downstream effects, including important measures such as lower blood glucose (in diabetics and non-diabetics) and decreased liver enzymes. Mid-stage diabetes data has been outstanding. Glycemic data from the phase 3 EQUATE (OB-301) study was presented at 2009 ADA annual meeting. After 28 weeks of treatment, blood sugar levels, as measured by hemoglobin A1c (HbA1c), were lower in the patients treated with Qnexa, while the patients in the placebo group had a significant increase in their HbA1c levels (p<0.0001). The placebo-adjusted reductions in HbA1c for patients taking Qnexa were 0.11 percent and 0.10 percent for the full-dose and mid-dose groups (p<0.0001). Currently the company is running a phase 2 study on diabetes.

Importantly, there were no serious adverse events in the study. Moreover, on a validated depression scale (PHQ-9), Qnexa showed improvement over placebo, which is consistent with data from earlier but smaller trials. The most common adverse effects were in line with expectations, which include paresthesia (20% in the full-dose arm, 15% mid-dose, and 3% pbo), dry mouth (18%, 12%, 0%), altered taste (15%, 8%, 0%), and constipation (11%, 6%, 6%).

What’s still to come: EQUIP and CONQUER data on track for mid- 2009. EQUIP is a Phase 3 trial evaluating Qnexa (low- and full-dose) in 1,250 morbidly obese subjects while CONQUER is testing Qnexa (mid- and full-dose) in overweight subjects with co-morbidities. We expect the CONQUER study, a large ongoing phase 3 study that includes diabetic and pre-diabetic subjects, will further demonstrate the efficacy of Qnexa for weight loss and effective management of glycemic control in diabetic and non-diabetic patients. Positive trial data are expected to lead to a year end 2009 NDA filing. Full approval in both obesity and type 2 diabetes, along with a strong worldwide commercialization partner to market it, makes Qnexa a potential billion dollar drug.

Vivus current trades with a market capitalization of only $410 million. Management exited the first quarter 2009 with $165 million in cash on hand, positive initial phase III data on a potential blockbuster multi-billion dollar drug, and two additional niche multi-hundred million dollar phase III drugs in sexual dysfunction. The key wildcard events over the next few quarters include the 56-week phase III data on Qnexa from the EQUIP and CONQUER clinical trials -- expected in the third quarter 2009, and the initial phase III data on Avanafil -- expected in the fourth quarter of 2009. Vivus expects to exit 2009 with over $100 million cash in hand.

By almost all calculations, the stock looks still significantly undervalued. However, the risks of clinical development are high and getting drugs past the U.S. FDA, specifically in the area of behaviorally modification such as obesity, has been difficult. Finding a partner maybe is a better way to move the drug forward.

Management is likely to start entertaining partnership discussions on Qnexa, and potentially even Avanafil and Luramist, later in 2009. Zacks.com stated:

Vivus would be an extremely attractive acquisition target for a larger pharmaceutical company. The acquisition of Vivus brings in three phase III candidates -- something most big pharma companies are in desperate need of. As visibility on Qnexa and Avanafil improve, we would not be surprised to see interest from potential suitors soar.

Disclosure: Long VVUS.

Comments

[PhillyDan:]

Only 756 patients in a 28 week study, not a significant study size. Exclusions for this study read like a medical dictionary. Weight loss results were achieved with highest dosage of both parts of the combo drug. Qnexa needs long term safety data like Lorcaserin has achieved with the two year Bloom study with over 3000 patients enrolled. They have the Sequel study which is an extension of the Conquer study to provide this data. Qnexa will not be ready for NDA until late 3rd quarter of 2010 and the earliest it could receive PDUFA is July or August 2011.

Safety and tolerability will be more favorably viewed than weight loss efficacy by the FDA. Most Doctors don't like prescribing combo drugs because of the "unintended consequences from overlapping side effects". Phentermine raises concern with a number of MD's because it only can be prescribed for a certain amount of time, then needs to be stopped and restarted.

In my opinion, Qnexa does have a lot of potential but still needs to prove itself in safety and tolerability. What the author conveniently forgot to mention is the dropout rate of patients in the Qnexa study which is quite high.

The Blossom results for Lorcaserin will be announced in September. The Blossom study enrolled over 4000 patients at over 131 clinical centers around the United States. In addition, the Bloom-DM study will be completed soon and that study is tailored to patients with Type-II diabetes. Arena will file NDA in December with expected PDUFA in October of 2010. Arena has their own manufacturing facility in Switzerland that is ramped up and ready to go. That facility already does contract manufacturing for other drug companies.

Recommend that you read about Ed Sussman's successful results on Medpage Today. Ed is a medical writer for MedPage who was overweight. He lost over 52 pounds (the likely assumption is that he was on Lorcaserin not the placebo) in 52 weeks. He was able to reduce both BP and Diabetes medications as a result of this weight loss.

The obesity market is very large and will be able to handle more than one player to provide treatment for people suffering from the effects of being overweight or obese. What the author and other proponents of either Lorcaserin or Contrave forget to mention in their zealousness to promote the one they favor is the fact that people are all different. Some people may do better on Lorcaserin, others may do better on Qnexa or Contrave to help them lose weight and improve the other secondary endpoints. The main thing is that they are SAFE first and tolerable. Efficacy is important but should be the third thing that is considered in MD's recommending what to prescribe for their overweight and obese patients.

I also strongly recommend you do your own due diligence if you wish to invest in any or all of these three companies. Based on your own due diligence and research, you will make an informed decision on which of the three (and there will be more, in fact Neuro Search is another company with a promising obesity drug candidate) is the best investment for you.

Jul 08 02:06 PM

[66shelby:]

Great post, PhillyDan, especially about the safety concerns of all the drugs. Until (sufficient) long-term data is revealed, I feel that most clinicians would steer clear of said medications except in the most extreme circumstances.

Jul 08 11:57 PM

[pharmaman:]

Hey PhillyDan,
Yours is a well considered, analytical response.
Why could the author of this article not have done his homework?
Your analysis makes the author if this article look like a dilettante merely interested in getting an article on the web. I would like to hear his response.

Pharmaman


On Jul 08 02:06 PM PhillyDan wrote:

> Only 756 patients in a 28 week study, not a significant study size.
> Exclusions for this study read like a medical dictionary. Weight
> loss results were achieved with highest dosage of both parts of the
> combo drug. Qnexa needs long term safety data like Lorcaserin has
> achieved with the two year Bloom study with over 3000 patients enrolled.
> They have the Sequel study which is an extension of the Conquer study
> to provide this data. Qnexa will not be ready for NDA until late
> 3rd quarter of 2010 and the earliest it could receive PDUFA is July
> or August 2011.
>
> Safety and tolerability will be more favorably viewed than weight
> loss efficacy by the FDA. Most Doctors don't like prescribing combo
> drugs because of the "unintended consequences from overlapping side
> effects". Phentermine raises concern with a number of MD's because
> it only can be prescribed for a certain amount of time, then needs
> to be stopped and restarted.
>
> In my opinion, Qnexa does have a lot of potential but still needs
> to prove itself in safety and tolerability. What the author conveniently
> forgot to mention is the dropout rate of patients in the Qnexa study
> which is quite high.
>
> The Blossom results for Lorcaserin will be announced in September.
> The Blossom study enrolled over 4000 patients at over 131 clinical
> centers around the United States. In addition, the Bloom-DM study
> will be completed soon and that study is tailored to patients with
> Type-II diabetes. Arena will file NDA in December with expected PDUFA
> in October of 2010. Arena has their own manufacturing facility in
> Switzerland that is ramped up and ready to go. That facility already
> does contract manufacturing for other drug companies.
>
> Recommend that you read about Ed Sussman's successful results on
> Medpage Today. Ed is a medical writer for MedPage who was overweight.
> He lost over 52 pounds (the likely assumption is that he was on Lorcaserin
> not the placebo) in 52 weeks. He was able to reduce both BP and Diabetes
> medications as a result of this weight loss.
>
> The obesity market is very large and will be able to handle more
> than one player to provide treatment for people suffering from the
> effects of being overweight or obese. What the author and other proponents
> of either Lorcaserin or Contrave forget to mention in their zealousness
> to promote the one they favor is the fact that people are all different.
> Some people may do better on Lorcaserin, others may do better on
> Qnexa or Contrave to help them lose weight and improve the other
> secondary endpoints. The main thing is that they are SAFE first and
> tolerable. Efficacy is important but should be the third thing that
> is considered in MD's recommending what to prescribe for their overweight
> and obese patients.
>
> I also strongly recommend you do your own due diligence if you wish
> to invest in any or all of these three companies. Based on your own
> due diligence and research, you will make an informed decision on
> which of the three (and there will be more, in fact Neuro Search
> is another company with a promising obesity drug candidate) is the
> best investment for you.

Jul 09 05:58 PM

[pharmaman:]

Hey PhillyDan,

What do you think are the shortcomings of Lorcaserin -- do you have an analysis on that?

Pharmaman


On Jul 08 02:06 PM PhillyDan wrote:

> Only 756 patients in a 28 week study, not a significant study size.
> Exclusions for this study read like a medical dictionary. Weight
> loss results were achieved with highest dosage of both parts of the
> combo drug. Qnexa needs long term safety data like Lorcaserin has
> achieved with the two year Bloom study with over 3000 patients enrolled.
> They have the Sequel study which is an extension of the Conquer study
> to provide this data. Qnexa will not be ready for NDA until late
> 3rd quarter of 2010 and the earliest it could receive PDUFA is July
> or August 2011.
>
> Safety and tolerability will be more favorably viewed than weight
> loss efficacy by the FDA. Most Doctors don't like prescribing combo
> drugs because of the "unintended consequences from overlapping side
> effects". Phentermine raises concern with a number of MD's because
> it only can be prescribed for a certain amount of time, then needs
> to be stopped and restarted.
>
> In my opinion, Qnexa does have a lot of potential but still needs
> to prove itself in safety and tolerability. What the author conveniently
> forgot to mention is the dropout rate of patients in the Qnexa study
> which is quite high.
>
> The Blossom results for Lorcaserin will be announced in September.
> The Blossom study enrolled over 4000 patients at over 131 clinical
> centers around the United States. In addition, the Bloom-DM study
> will be completed soon and that study is tailored to patients with
> Type-II diabetes. Arena will file NDA in December with expected PDUFA
> in October of 2010. Arena has their own manufacturing facility in
> Switzerland that is ramped up and ready to go. That facility already
> does contract manufacturing for other drug companies.
>
> Recommend that you read about Ed Sussman's successful results on
> Medpage Today. Ed is a medical writer for MedPage who was overweight.
> He lost over 52 pounds (the likely assumption is that he was on Lorcaserin
> not the placebo) in 52 weeks. He was able to reduce both BP and Diabetes
> medications as a result of this weight loss.
>
> The obesity market is very large and will be able to handle more
> than one player to provide treatment for people suffering from the
> effects of being overweight or obese. What the author and other proponents
> of either Lorcaserin or Contrave forget to mention in their zealousness
> to promote the one they favor is the fact that people are all different.
> Some people may do better on Lorcaserin, others may do better on
> Qnexa or Contrave to help them lose weight and improve the other
> secondary endpoints. The main thing is that they are SAFE first and
> tolerable. Efficacy is important but should be the third thing that
> is considered in MD's recommending what to prescribe for their overweight
> and obese patients.
>
> I also strongly recommend you do your own due diligence if you wish
> to invest in any or all of these three companies. Based on your own
> due diligence and research, you will make an informed decision on
> which of the three (and there will be more, in fact Neuro Search
> is another company with a promising obesity drug candidate) is the
> best investment for you.

Jul 09 06:26 PM

[dakyne:]

Nice post Philly Dan. I'm astounded at what passes as (professional) analysis these days.

You touched upon the high points: the limited data points for the Qnexa clinical trials and the long exclusion criteria, relative to Lorcaserin's. There are reasons for this discrepancy: the adverse side effects of phentermine and topamax (both generic compounds, btw). Even if approved, and prescribed to a limited pool, the profit margin on Qnexa would be questionable.


On Jul 08 02:06 PM PhillyDan wrote:

> Only 756 patients in a 28 week study, not a significant study size.
> Exclusions for this study read like a medical dictionary. Weight
> loss results were achieved with highest dosage of both parts of the
> combo drug. Qnexa needs long term safety data like Lorcaserin has
> achieved with the two year Bloom study with over 3000 patients enrolled.
> They have the Sequel study which is an extension of the Conquer study
> to provide this data. Qnexa will not be ready for NDA until late
> 3rd quarter of 2010 and the earliest it could receive PDUFA is July
> or August 2011.
>
> Safety and tolerability will be more favorably viewed than weight
> loss efficacy by the FDA. Most Doctors don't like prescribing combo
> drugs because of the "unintended consequences from overlapping side
> effects". Phentermine raises concern with a number of MD's because
> it only can be prescribed for a certain amount of time, then needs
> to be stopped and restarted.
>
> In my opinion, Qnexa does have a lot of potential but still needs
> to prove itself in safety and tolerability. What the author conveniently
> forgot to mention is the dropout rate of patients in the Qnexa study
> which is quite high.
>
> The Blossom results for Lorcaserin will be announced in September.
> The Blossom study enrolled over 4000 patients at over 131 clinical
> centers around the United States. In addition, the Bloom-DM study
> will be completed soon and that study is tailored to patients with
> Type-II diabetes. Arena will file NDA in December with expected
> PDUFA in October of 2010. Arena has their own manufacturing facility
> in Switzerland that is ramped up and ready to go. That facility
> already does contract manufacturing for other drug companies.
>
> Recommend that you read about Ed Sussman's successful results on
> Medpage Today. Ed is a medical writer for MedPage who was overweight.
> He lost over 52 pounds (the likely assumption is that he was on Lorcaserin
> not the placebo) in 52 weeks. He was able to reduce both BP and
> Diabetes medications as a result of this weight loss.
>
> The obesity market is very large and will be able to handle more
> than one player to provide treatment for people suffering from the
> effects of being overweight or obese. What the author and other
> proponents of either Lorcaserin or Contrave forget to mention in
> their zealousness to promote the one they favor is the fact that
> people are all different. Some people may do better on Lorcaserin,
> others may do better on Qnexa or Contrave to help them lose weight
> and improve the other secondary endpoints. The main thing is that
> they are SAFE first and tolerable. Efficacy is important but should
> be the third thing that is considered in MD's recommending what to
> prescribe for their overweight and obese patients.
>
> I also strongly recommend you do your own due diligence if you wish
> to invest in any or all of these three companies. Based on your
> own due diligence and research, you will make an informed decision
> on which of the three (and there will be more, in fact Neuro Search
> is another company with a promising obesity drug candidate) is the
> best investment for you.

Jul 15 06:54 PM

[Penn Bioinv...:]

Looked a bunch of ARNA fans posted comments here. Thanks for Philly Dan's comment, although I disagree with his opinion, but which is detailed and thoughtful. He did his homework. As to ARNA, I have no interest to bash. Your money, your decision. Don't regret if later it turned out you picked the wrong stock. I presented the chance to pick the winner to you, which is VVUS. I have comment on Philly Dan's comments before. For people not aware of that, here is for you:
Just to point out VVUS's obesity drug is far superior than ARNA.

Let the fact to speak out for themselves (ARNA vs. VVUS)

lost at least 5% weight:
arna 66.40 arna placebo 32.10%
vvus 66% vvus placebo 15%

lost at least 10% weight:
arna 36.20% arna placebo 13.60%
vvus 41% vvus placebo 7%

lost at least 15% weight
arna no data
vvus 19% vvus placebo 2%

retention after 1 year:
arna 55%
vvus 70%

those results speak for themselves.

Jul 17 10:09 PM

[Penn Bioinv...:]

Where are all those bashers???

Sep 09 08:24 AM

[Penn Bioinv...:]

Where are all those bashers? Come out and check the big day for VVUS.

Sep 09 08:24 AM