Study Finds Significant Improvements In Patients With Obstructive Sleep Apnea Treated With Phentermine And Topiramate Extended-Release Capsules

MOUNTAIN VIEW, Calif., Nov. 12, 2012 /PRNewswire/ -- VIVUS, Inc. (NASDAQ: VVUS) today announced that a study published in the journal SLEEP (2012; 35(11):1529-1539) found that patients with moderate to severe obstructive sleep apnea (OSA) taking phentermine and topiramate extended-release capsules achieved significant improvements in key measures of OSA and cardiovascular risk factors along with weight loss during the 28-week trial.

OSA is a chronic and potentially serious sleep disorder in which breathing is abnormally shallow ("hypopnea") or stops altogether ("apnea") for at least 10 seconds. These repetitive events are associated with collapse of the upper airway during sleep, and may occur 5 to 30 or more times per hour. Although many cases are unrecognized, symptoms may include snoring, fatigue or sleepiness during the day.

OSA afflicts approximately 3% to 7% of the U.S. population. Data from the Wisconsin Cohort Study indicate that the prevalence of OSA in people aged 30-60 years is 9-24% for men and 4-9% for women.

OSA is associated with an increased risk of hypertension, cardiovascular disease, myocardial infarction, stroke and increased mortality.

The current standard of care treatment for OSA is "positive airway pressure" (PAP) in which the upper airway is kept open by increased air pressure, but PAP provides benefits only when used consistently. Many patients find PAP to be inconvenient or uncomfortable, and compliance with PAP treatment limits its effectiveness.

A safe and effective pharmacologic treatment for OSA could be useful and more acceptable to some patients than PAP, but no drug is currently approved to treat OSA.

In the study recently reported in SLEEP, 45 obese adults who were not using PAP were randomized to placebo or treatment with phentermine and topiramate extended-release capsules for 28 weeks. Both groups received intensive lifestyle modification counseling. The primary endpoint was change in the apnea-hypopnea index (AHI), a measure of the average number of breathing interruptions per hour during sleep. An AHI of 5-15 is considered mild, 15-30 moderate, and severe if  >30. The average AHI at baseline in both treatment groups was about 45, indicating that, on average, subjects had severe OSA at the beginning of the study.

By the end of the study, the number of apnea-hypopnea events in the phentermine and topiramate extended-release capsules group was reduced from an average of 44 events per hour (severe) to 14 events per hour (mild) at Week 28. The placebo-adjusted LS mean change Week 28 was -14.9 (p=0.0084).

Cardiovascular and metabolic risk factors, such as systolic blood pressure and mean overnight oxygen saturation, were also improved during the study.

At Week 28, the LS mean percent change in weight from baseline was -10.3% in the phentermine and topiramate extended-release capsules group and -4.2% in the placebo group (p=0.0006) in which subjects received only lifestyle modification counseling. More subjects in the phentermine and topiramate extended-release capsules group (54.5%) achieved at least 10% weight loss compared with 13.0% in the placebo group (p=0.0044).

The most common adverse events reported during the study included dry mouth, altered taste, sinusitis, and upper airway infection.

"Obstructive sleep apnea is a serious condition associated with potentially deadly cardiovascular and metabolic events for the more than 15 million patients living with the disease. Unfortunately, there are no drug treatments available for the condition, and because current treatment options are limited to devices or surgery, patient compliance is low," stated David Winslow, MD., the principal investigator of the study and lead author of the paper. "These positive data, from what is considered a sizable study for OSA, are exciting for those of us in the medical community treating obese patients with this condition."

This randomized, placebo-controlled, proof-of-concept study suggests that phentermine and topiramate extended-release capsules combined with lifestyle modification may be useful in the treatment of patients with obstructive sleep apnea who are unable to use PAP therapy. Additional and larger studies are required to explore these results more thoroughly.

Phentermine and topiramate extended-release capsule is not approved for the treatment of obstructive sleep apnea. This study was funded by VIVUS, Inc.

About VIVUS

VIVUS^® is a biopharmaceutical company commercializing and developing innovative, next-generation therapies to address unmet needs in obesity, sleep apnea, diabetes and sexual health for U.S., Europe and other world markets. Qsymia is also in phase 2 clinical development for the treatment of type 2 diabetes and obstructive sleep apnea. For more information about the company, please visit 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," "estimate," "expect," "intend," "likely," "may," "plan," "potential," "predict," "opportunity" and "should," among others. 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, our lack of commercial experience with Qsymia in the U.S.; the timing of initiation and completion of the clinical studies required as part of the approval of Qsymia by the United States Food and Drug Administration, or FDA; the response from the FDA to the data that VIVUS will submit relating to post-approval clinical studies; the impact of the indicated uses and contraindications contained in the Qsymia label and the REMS requirements; the impact of distribution of Qsymia through a certified pharmacy network; whether or not the FDA approves our amendment to the REMS for Qsymia, which, if approved, would allow dispensing through select retail pharmacies to increase access while meeting all requirements of the REMS; that we may be required to provide further analysis of previously submitted clinical trial data; our  appeal of the negative opinion of the European Medicines Agency's, or EMA, Committee for Medicinal Products for Human Use, or CHMP, for the Marketing Authorization Application, or MAA, for Qsymia; our ability to successfully commercialize or establish a marketing partnership for avanafil, which will be marketed in the U.S. under the name STENDRA™, or our partner's ability to obtain and maintain regulatory approval to manufacture and adequately supply avanafil to meet demand; our history of losses and variable quarterly results; substantial competition; risks related to the failure to protect our intellectual property and litigation in which we may become involved; uncertainties of government or third party payer reimbursement; our reliance on sole source suppliers; our limited sales and marketing and manufacturing experience; our reliance on third parties and our collaborative partners; our failure to continue to develop innovative investigational drug candidates and drugs; risks related to the failure to obtain FDA or foreign authority clearances or approvals and noncompliance with FDA or foreign authority regulations; our ability to demonstrate through clinical testing the safety and effectiveness of our investigational drug candidates; the timing of initiation and completion of clinical trials and submissions to foreign authorities; the volatility and liquidity of the financial markets; our liquidity and capital resources; and our expected future revenues, operations and expenditures. As with any pharmaceutical in development, there are significant risks in the development, the regulatory approval, and commercialization of new products. There are no guarantees that our products will receive regulatory approval outside the United States for any indication or prove to be commercially successful. VIVUS does not undertake an obligation to update or revise any forward-looking statements. Investors should read the risk factors set forth in VIVUS' Form 10-K for the year ending December 31, 2011, and periodic reports filed with the Securities and Exchange Commission.

SOURCE VIVUS, Inc.