Weight Loss Drug Qnexa Reduces Hemoglobin A1c By 1.6% & Wt By 9%

Drug developer Vivus Inc last Thursday, announced prelim results for the first of three late-stage trials and found that obese patients treated with the highest dose of its experimental drug Qnexa on average lost 9.2 percent of their weight.  Qnexa is a combination of phentermine -- half of the recalled fen-phen diet pill -- and the epilepsy drug Topamax, or topiramate.

Qnexa(TM), an investigational drug, for the glycemic management of obese type 2 diabetics. The DM-230 study met its primary endpoint of demonstrating glycemic control as measured by a reduction of hemoglobin A1c of 1.6% from 8.8% to 7.2% for subjects treated with Qnexa, as compared to 1.1% from 8.5% to 7.4% in the placebo group at 56 weeks. Subjects in the study were actively managed according to ADA standards of care with respect to diabetes medications and lifestyle. For subjects treated with placebo, significant increases in the number and doses of concurrent anti-diabetic medications were required to bring about the observed reduction in HbA1c. By contrast, concurrent anti-diabetic medications were actually reduced over the course of the trial in subjects treated with Qnexa.

The DM-230 study was designed as a continuation study to the OB-202 diabetes study. The OB-202 study was a 28-week, randomized, double-blind, placebo-controlled, efficacy and safety study of Qnexa in the glycemic management of 206 obese type 2 diabetics. The DM-230 study enrolled 130 subjects at 10 study sites completing OB-202 to continue, in a blinded fashion as previously randomized for an additional 28 weeks. The results of the DM-230 study include assessments from the start of the OB-202 study through the end of the DM-230 study in this population, for a total treatment period of 56 weeks.

Fasting plasma glucose levels were reduced in subjects treated with Qnexa from 176 mg/dL to 133 mg/dL, as compared to a decrease from 171 mg/dL to 145 mg/dL for the placebo group (p=0.02). Over 56 weeks subjects treated with Qnexa also lost 9.4% of their baseline body weight, or 20.5 pounds, as compared to 2.7%, or 6.1 pounds, for the placebo group (p<0.0001). Subjects treated with Qnexa had reductions in blood pressure, triglycerides and waist circumference. Both treatment groups had a study completion rate greater than 90%.

"The results from DM-230 confirm our belief that Qnexa may be an appropriate treatment for type 2 diabetes given the reduction in HbA1c of 1.6% combined with weight loss of 9.4% seen in the most recent study," commented Leland Wilson, president and chief executive officer of VIVUS. "Historically, diabetic patients have a difficult time losing weight. With Qnexa, patients were able to lose over 20 pounds and importantly keep it off throughout the 56 week study with no rebound."

"The improved glycemic control demonstrated by the Qnexa treatment group in OB-202 continued as expected for an additional 28 weeks. More importantly, Qnexa's safety profile was favorable as demonstrated by high completion rates," commented a principal investigator of the study, Dr. W. Timothy Garvey, Professor of Medicine and Chair of the Department of Nutrition Sciences at the University of Alabama at Birmingham. "I am particularly impressed by the fact that treatment with Qnexa has the greatest effect in those patients that are most in need of treatment. Patients with baseline HbA1c greater than 8% had an overall reduction in HbA1c of 2.1% in 56 weeks, combined with the level of weight loss that is unheard of with current oral treatments. This phase 2 study is encouraging and indicates that Qnexa has the potential to greatly add to our armament of drugs for the treatment of type 2 diabetes."

The most common drug-related adverse events reported over the year for the treatment and placebo groups, respectively, were paresthesia (19%, 0%), constipation (13%, 4%) and nausea (12%, 6%). These adverse events decreased in frequency during the last six months as compared to the first six months to: paresthesia 5%, constipation 5% and nausea 1% in the treatment group. Subjects were monitored for depression and suicidality using the PHQ-9 questionnaire, the FDA's preferred mental health assessment tool. Subjects treated with Qnexa demonstrated greater improvements in PHQ-9 scores from baseline to the end of the study than the placebo group, providing further assurance that Qnexa treatment does not produce significant adverse mood changes or suicidality.

Despite a mean baseline HbA1c level of 8.7%, 53% of the subjects treated with Qnexa were able to achieve the ADA recommended goal of 7.0% or lower, versus 40% of the subjects in the placebo arm (p<0.05). The incidence of hypoglycemia in the treatment and placebo arms were similar (12% and 9%, respectively). Qnexa was well-tolerated, with no treatment-related serious adverse events.
Release: VIVUS R&D Day December 12, 2008