VIVUS, Inc. (Nasdaq: VVUS) today announced positive top-line results from a two-year study of QNEXA® (phentermine/topiramate) Controlled Release Capsules, an investigational therapy for treatment of obesity, a condition that affects approximately one-third of adult Americans.
The findings come from the SEQUEL study (OB-305), a 52-week extension study for a subset of patients who completed the previously reported 56-week CONQUER study. The total study period was 108 weeks. SEQUEL included 675 obese or overweight patients, all of whom had two or more weight related co-morbidities, and an average baseline BMI of 36.1.
Patients in the study taking the top dose of QNEXA achieved and maintained average weight loss through two years of 11.4% of their initial body weight, or 26 pounds (ITT-LOCF). Consistent with the first year experience, QNEXA therapy was well tolerated, with no new or unexpected adverse events. The most common side effects seen were constipation, tingling, dry mouth, altered taste and insomnia.
Weight loss with QNEXA in SEQUEL was associated with statistically significant improvements in weight-related co-morbidities such as hypertension, dyslipidemia and diabetes. Among patients without diabetes at baseline, the incidence of new onset of type 2 diabetes was reduced by 54% and 76% (mid- and top-dose, respectively) as compared to placebo.
SEQUEL was a double-blind, placebo-controlled, three-arm, prospective study. Patients continued receiving the same treatment they had been randomized to in the CONQUER study in a blinded fashion: either once-a-day treatment with top-dose QNEXA>
Specific SEQUEL findings include the following primary endpoints:
- Patients taking top- and mid-dose QNEXA achieved and maintained weight loss over two years of 11.4% and 10.4% of their initial body weight, respectively, as compared to placebo-treated patients with 2.5% weight loss (ITT-LOCF, p<0.0001).
- A majority of all patients taking QNEXA exceeded 10% weight loss, the goal established by the National Institutes of Health (NIH) to decrease the severity of obesity-associated risk factors.
- The percentage of patients achieving categorical weight loss of at least 5%, 10% and 15% on both QNEXA doses was statistically significant compared to placebo:
Treatment-emergent serious adverse event rates in SEQUEL were low (top-dose = 4.1%; mid-dose = 2.6%) and similar to placebo (4.0%), with no drug-related serious adverse events reported.
The completion rate in SEQUEL was approximately 83% for both QNEXA doses and 86% for the placebo group. Discontinuations due to adverse events were 3.9% and 4.1% for the mid- and top-dose, respectively; and 2.6% for the placebo group; with no single adverse event leading to discontinuation in more than 1% of patients.
Additionally, SEQUEL data confirms previous safety findings, with no evidence of suicidality and no reports of suicidal attempts or behavior. Depression assessments, as measured by the PHQ-9 clinical depression scale, improved from baseline for all treatment groups.
The incidence of targeted medical events for sleep disorders, depression, anxiety, cardiac disorders and cognitive disorders in SEQUEL was lower than observed during the one-year CONQUER study.
Similar to previously presented data, effects of QNEXA in SEQUEL on heart rate were small and seen in conjunction with improvements in blood pressure from baseline. There were no clinically relevant decreases of serum bicarbonate in QNEXA-treated patients compared to placebo in year two of SEQUEL.
Across the entire QNEXA development program (4,323 patients), including the two-year data in SEQUEL, serious cardiovascular and neurovascular adverse event rates in patients taking QNEXA were similar to placebo with a relative risk of 0.59 (95% CI: 0.33-1.06). No teratogenic effects were observed across the entire development program in patients taking QNEXA.
"These two-year data provide further reassurance that QNEXA may fill a significant medical need for this at-risk, co-morbid population struggling to lose weight and keep it off," said Leland Wilson, chief executive officer of VIVUS. "We look forward to presenting and publishing additional data from SEQUEL, including secondary efficacy endpoints for decreasing co-morbidity risks, in the future."
SOURCE VIVUS, Inc.