Thursday, December 11, 2008

Qnexa--The next frontier in weight management drugs--or is it?

Below my pontificating you will see a press release for a new weight loss medication, Qnexa.

My initial impressions:

1. This looks like the new twist on the old "phen-fen," phentermine being the common ingredient in both, with the problem compound, fenfluramine, being replaced with topiramate (Topamax). Topiramate is a mood stabilizing drug that has been found to have weight loss effects in some people and has been used in an off-label fashion for this purpose.

2. For the record, I've collected a bunch of references on potential side effects reported with topiramate, including: kidney stones, reduced testosterone in males, dry mouth, nausea, reduced sweating, body temperature regulation (which could become an issue if you're following directions and exercising more), cerebellar cognitive affective syndrome, and delusional parasitosis. (That's when you have the creepy feeling that bugs are crawling all over you when none are there.) References are provided below.

3. People aren't overweight because they have phentermine or topiramate deficiencies. Obesity is a huge target for drug research because there's such a huge market--it's a gold mine for anyone who can create and patent a medication that can stay on the market without its negative side effects forcing it to be yanked. My concern is once this med is used in large numbers some of these side effects are going to become huge problems.

4. Just beware if you decide to try this medication when it becomes available. It's not 100% foolproof. Anyone who prescribes you this medication without advising you of these potential problems may not fully understand how this medication works. And that's your red flag of a potential problem. Be informed!

Otoom S, Batieneh H, Hassan Z, Daoud A. Effects of long-term use Topiramate on fertility and growth parameter in adult male rats. Neuro Endocrinol Lett. 2004 Oct;25(5):351-5.

Sharief M, Viteri C, Ben-Menachem E, Weber M, Reife R, Pledger G, Karim R. Double-blind, placebo-controlled study of topiramate in patients with refractory partial epilepsy. Epilepsy Res 1996 Nov;25(3): 217-24.

Incecik F, Herguner MO, Altunbasak S. Topiramate associated hypohidrosis and hyperthermia. Indian Pediatr. 2008 Mar;45(3):238-40.

Cerminara C, Seri S, Bombardieri R, Pinci M, Curatolo P. Hypohidrosis during topiramate treatment: a rare and reversible side effect. Pediatr Neurol 2006 May;34(5):392-4.

Baillieux H, Verslegers W, Paquier P, De Deyn PP, Mariën P. Cerebellar cognitive affective syndrome associated with topiramate. Clin Neurol Neurosurg. 2008 May;110(5):496-9.

Fleury V, Wayte J, Kiley M.
Topiramate-induced delusional parasitosis. J Clin Neurosci. 2008 May;15(5):597-9.

Vega D, Maalouf NM, Sakhaee K. Increased propensity for calcium phosphate kidney stones with topiramate use. Expert Opin Drug Saf 2007 Sep;6(5):547-57.

Koçer A, Dikici S, Atakay S, Okuyucu E. Serum Uric Acid and Lipid Levels While Taking Topiramate for Migraine. Headache. 2007 Dec 27.

Qnexa Meets Primary Endpoint by Demonstrating Superior Weight Loss over
Components and Placebo in the 28-Week Equate Study (OB-301)

Subjects on Full-Dose Qnexa Attained an Average Weight Loss of 9.2% with
66% Achieving 5% or Greater Weight Loss

MOUNTAIN VIEW, Calif.--(BUSINESS WIRE)--Dec 11, 2008 - VIVUS, Inc.
(NASDAQ: VVUS), a pharmaceutical company dedicated to the development
and commercialization of novel therapeutic products, today announced
positive results from the EQUATE study (OB-301), a 28-week, phase 3
obesity trial conducted at 32 sites with QnexaTM, an investigational
drug. The EQUATE study met the primary endpoint by demonstrating
superior weight loss with both the full-dose and mid-dose of Qnexa, as
compared to the individual components and placebo. Subjects treated with
full-dose and mid-dose Qnexa had an average weight loss of 9.2% and 8.5%
respectively, as compared to weight loss of 1.7% reported in the placebo
group (ITT LOCF p<0.0001). Average weight loss was 19.8 pounds and 18.2
pounds in the treatment arms as compared to 3.3 pounds in the placebo
group. Qnexa was well-tolerated, with no drug-related serious adverse
events in the study.

"The results from the EQUATE trial once again confirmed our belief in
Qnexa. In addition to hitting the primary endpoints of the study with
the full-dose, we were also able to show excellent results with the
mid-dose of Qnexa," commented Leland Wilson, president and chief
executive officer of VIVUS. "The EQUATE study is the first of three
studies in the Qnexa phase 3 obesity program. Data from the EQUIP and
CONQUER studies, which combined enrolled over 3,750 subjects, is
expected in mid-2009."

The EQUATE study included 756 obese subjects (599 females and 157 males)
across 32 centers in the United States. The average baseline BMI of the
study population was 36.3 kg/ m2 and baseline weight was 223 pounds. The
proportion of patients losing 5% or more of their initial body weight
was 66% for full-dose, 62% for mid-dose and 15% for placebo (p<0.0001).
The proportion of patients losing 10% or more of their initial body
weight was 41% for full-dose, 39% for mid-dose and 7% for the placebo
group (p<0.0001).

The most common drug-related adverse events reported for the full-dose,
mid-dose and placebo group were paresthesia (20%, 15%, 3%), dry mouth
(18%, 12%, 0%), altered taste (15%, 8%, 0%) and constipation (11%, 6%,
6%). Reported drug related adverse events for depression and altered
mood were minimal (1.9%, 0.9% and 1.8% respectively) . Moreover,
individual depression assessments for each subject, as measured by
PHQ-9, demonstrated statistically significant improvements (p<0.05) from
baseline for both Qnexa treatment groups. Overall average completion
rate for the Qnexa treatment group was 71%.

Subjects in the EQUATE study had a 4-week dose titration period followed
by 24 weeks of treatment. The study was a randomized, double-blind,
placebo-controlled, 7-arm, prospective trial with subjects randomized to
receive once-a-day treatment with mid-dose Qnexa (7.5 mg phentermine/ 46
mg topiramate CR), full-dose Qnexa (15 mg phentermine/ 92 mg topiramate
CR), the respective phentermine and topiramate constituents, or placebo.
Subjects were asked to follow a hypocaloric diet representing a
500-calorie/ day deficit and advised to implement a simple lifestyle
modification program.

About the Qnexa Phase 3 Obesity Program

In addition to the EQUATE study, the phase 3 Qnexa program includes two
pivotal, double-blind, placebo-controlled, multi-center studies that
will compare the efficacy and safety of Qnexa to placebo during a
56-week treatment period. The first year long study, known as EQUIP
(OB-302), has enrolled approximately 1,250 morbidly obese adult subjects
with a Body Mass Index (BMI) of 35 or greater with or without controlled
co-morbidities. The second trial, known as CONQUER (OB-303), has
enrolled overweight and obese adult subjects with BMIs from 27 to 45 and
at least two co-morbid conditions, such as hypertension, dyslipidemia
and type 2 diabetes. The co-primary endpoints for these studies are the
mean percent weight loss and the percentage of subjects achieving a
weight loss of five percent or more. Results from these studies are
expected mid-2009. In total the phase 3 program has enrolled
approximately 4,500 subjects.

VIVUS R&D Day December 12, 2008

As previously announced, VIVUS will host a Research and Development Day
Event on Friday, December 12, 2008 at 8:00 a.m. ET in New York City.
Additional details on the data released today will be presented.

To access the webcast of this event, please visit:
http://phx.corporat phoenix.zhtml? p=irol-eventDeta ils&c=79161& ev
entID=2046581 or VIVUS' Investors site at http://www.vivus. com. Replay
will also be available on demand from the website at the conclusion of
the program and will run through December 31, 2008.

If you are interested in attending, please contact Brian Korb at The
Trout Group at 646 378 2923 or bkorb@troutgroup. com.


VIVUS, Inc. is a pharmaceutical company dedicated to the development and
commercialization of novel therapeutic products. The current portfolio
includes investigational product candidates addressing obesity, diabetes
and sexual health. The investigational pipeline includes: QnexaTM, which
is in phase 3, for the treatment of obesity and has completed a phase 2
study for the treatment of type 2 diabetes; avanafil, for which a phase
2 study has been completed for the treatment of erectile dysfunction
("ED") and LuramistTM (Testosterone MDTS(r)), for which a phase 2 study
has been completed for the treatment of Hypoactive Sexual Desire
Disorder ("HSDD"). MUSE(r) is approved and currently on the market for
the treatment of ED. For more information on clinical trials and
products, please visit the company's web site at http://www.vivus. com/.

Certain statements in this press release are forward-looking within the
meaning of the Private Securities Litigation Reform Act of 1995. These
statements may be identified by the use of forward-looking words such as
"anticipate, " "believe," "forecast," "estimated" and "intend," among
others. These forward-looking statements are based on VIVUS' current
expectations and actual results could differ materially. There are a
number of factors that could cause actual events to differ materially
from those indicated by such forward-looking statements. These factors
include, but are not limited to, substantial competition; uncertainties
of patent protection and litigation; uncertainties of government or
third party payer reimbursement; reliance on sole source suppliers;
limited sales and marketing efforts and dependence upon third parties;
risks related to the development of innovative products; and risks
related to failure to obtain FDA clearances or approvals and
noncompliance with FDA regulations. As with any pharmaceutical under
development, there are significant risks in the development, regulatory
approval and commercialization of new products. There are no guarantees
that future clinical studies discussed in this press release will be
completed or successful or that any product will receive regulatory
approval for any indication or prove to be commercially successful.
VIVUS does not undertake an obligation to update or revise any
forward-looking statement. Investors should read the risk factors set
forth in VIVUS' Form 10-K for the year ended December 31, 2007 and
periodic reports filed with the Securities and Exchange Commission.

1 comment:

Marcus said...

With all the weight loss pills in the market today, it is difficult to know which is bogus or not, which is safe or not. If ever you have to resort to meds that will aid your weight loss, make sure you consult it with your doctor first. Better yet, let your doctor prescribe which diet pill is best for you instead of taking chances with the newest weight loss pill out there. When it comes to your health, safety should be put first.