Qsymia for Weight Loss

Qsymia for Weight Loss 2017-01-30T13:56:27+00:00

The Problem

The prevalence of obesity continues to be a health concern that affects a large and growing proportion of the population, including more than one third (more than 78 million) of American adults. Worldwide more than 500 million people are obese. Obesity directly contributes to numerous life-threatening conditions: diabetes, cardiovascular disease, hypertension and stroke and is the second leading cause of preventable death in the U.S.

Beyond its impact on health, it is estimated that obesity economically accounts for 9.1% of U.S. annual health care spending – nearly $150 billion dollars. By 2030, if trends in the escalating rates of obesity continue, health care costs attributable to obesity may reach $956 billion, accounting for up to 18% of total health care costs, or $1 in every $6 spent on health care.

The Product

Qsymia in Las VegasQsymia® (phentermine and topiramate) Extended-release Capsules is an investigational, once-per-day, weight-loss therapy that combines low doses of two agents approved by the Food and Drug Administration (FDA), phentermine and topiramate, in a controlled-release formulation.

Status

The company resubmitted the Qsymia NDA on October 17, 2011. On November 3, 2011, we announced that the NDA was accepted for filing and review.

The FDA assigned a six-month, or class 2, review classification to the NDA, establishing April 17, 2012, as the Prescription Drug User Fee Act (PDUFA) target date.

The NDA resubmission seeks approval for the treatment of obesity, including weight loss and maintenance of weight loss for obese patients (BMI ≥ 30 kg/m2), or overweight patients (BMI ≥ 27 kg/m2) with weight-related co-morbidities such as hypertension, type 2 diabetes, dyslipidemia, or central adiposity (abdominal obesity). The proposed labeling includes a contraindication for women who are pregnant. The resubmission also includes a proposed Risk Evaluation and Mitigation Strategy (REMS).

Clinical Studies

In phase 2 and 3 clinical data to date, patients taking Qsymia have demonstrated statistically significant weight loss, glycemic control, and improvement in cardiovascular risk factors, when used in combination with a diet and lifestyle modification program. The most commonly reported side effects were tingling, dry mouth, constipation and altered taste.

EQUIP Study

The 56-week EQUIP study evaluated the efficacy and safety of the investigational drug Qsymia in 1,267 severely obese (BMI ≥35 kg/m²) patients across 91 sites in the U.S. The results from the EQUIP study were published in Obesity¹, the peer-reviewed journal of The Obesity Society. Highlights from the publication include:

  • Average weight loss for Qsymia patients who completed the EQUIP study was 14.4% and 6.7% with top dose Qsymia and low dose Qsymia, respectively, compared to 2.1% in the placebo group (p<0.0001);
  • LS Mean percent weight loss at week 56 was 10.9% and 5.1% (ITT-LOCF) for the top and low dose, respectively, as compared to 1.6% for the placebo group (p<0.0001);
  • Among patients who completed the top dose course of treatment, 83.5% lost ≥5%; 67.7% lost ≥10%; and 48.1% lost ≥15% of their baseline weight; and
  • Categorical weight loss from baseline (ITT-LOCF) was:
    ≥5% ≥10% ≥15%
    Top Dose 67%* 47%* 32%*
    Low Dose 45%* 19%* 7%†
    Placebo 17% 7% 3%

    *p < 0.0001 vs placebo
    †p < 0.05 vs placebo

The most commonly reported side effects in the EQUIP study were tingling (1.9%, 4.2%, and 18.8%) with placebo, low dose Qsymia and top dose Qsymia, respectively; dry mouth (3.7%, 6.7%, and 17.0%, respectively); constipation (6.8%, 7.9%, and 14.1%, respectively); altered taste (1.0%, 1.3%, and 8.4%, respectively); and insomnia (4.9%, 5.0%, and 7.8%, respectively). Rates of serious adverse events were the same across treatment groups. Most adverse events were seen early in treatment and there was a low dropout rate due to adverse events, 16.0% and 11.3% for top and low dose, respectively, compared to 8.4% for placebo.

CONQUER Study

The 56-week CONQUER study evaluated the efficacy and safety of Qsymia as well as improvements in co-morbidities studied as secondary endpoints, including cardiovascular, metabolic and inflammatory risk factors in 2,487 patients across 93 sites in the U.S. Results from the CONQUER study were published in The Lancet², a peer-reviewed journal. Highlights from the publication include:

  • LS Mean percent weight loss at week 56 was 7.8% and 9.8% (ITT-LOCF), respectively, for the mid and top dose as compared to 1.2% for the placebo group; and
  • Categorical weight loss from baseline (ITT-LOCF) was:
    ≥5% ≥10%
    Top Dose 70%* 48%*
    Mid Dose 62%* 37%*
    Placebo 21% 7%

    *p < 0.0001 vs placebo

  • Qsymia patients had improvements in co-morbidities and a reduction in the need for concomitant medications as compared to placebo.

The most commonly reported side effects in the CONQUER study were dry mouth (2%, 13%, and 21%) with placebo, mid dose Qsymia and top dose Qsymia, respectively; tingling (2%, 14% and 21%, respectively); constipation (6%, 15%, and 17%, respectively); insomnia (5%, 6%, and 10%, respectively); dizziness (3%, 7%, 10%, respectively); and altered taste (1%, 7%, and 10%, respectively). Rates of serious adverse events were similar across treatment groups: 4% with placebo, 3% with mid dose Qsymia and 5% with top dose Qsymia. Most adverse events were seen early in treatment and there was a low dropout rate due to adverse events, 12% and 19% for mid and top dose respectively, compared to 9% for placebo.

SEQUEL Study

The SEQUEL study was a one-year extension study of CONQUER and evaluated the long-term efficacy and safety of Qsymia in 676 overweight and obese subjects with cardiometabolic disease. The total study period was 108 weeks. Results from SEQUEL were published in The American Journal of Clinical Nutrition, a peer-reviewed journal. Highlights include:

  • Average weight loss at week 108 was 9.3% and 10.5%, respectively, for the mid and top dose of Qsymia as compared to 1.8% for the placebo group (LS mean ITT-LOCF);
  • Qsymia patients had improved cardiovascular and metabolic risk factors and a decrease in the need for associated medications in comparison with the placebo group; and
  • Placebo patients had a three times greater likelihood to progress to type 2 diabetes compared to subjects receiving top dose Qsymia and a two times greater likelihood than patients on mid dose Qsymia.

The most commonly reported side effects in the SEQUEL study were upper respiratory infection (18.5%, 17%, and 15.3% with placebo, mid dose Qsymia and top dose, respectively), constipation (3.1%, 7.2%, and 4.1%, respectively); tingling (0.0%, 0.7%, and 3.4%, respectively); sinus infection (7.9%, 7.8%, and 9.5%, respectively); dry mouth (0.4%, 0.7%, and 1.4%, respectively); and runny nose (11.5%, 8.5%, and 8.8%, respectively). There were no drug-related serious adverse events reported. The completion rate in SEQUEL was approximately 83% for both Qsymia doses and 86% for the placebo group. Discontinuations due to adverse events were 4.5% and 4.4% for the mid and top dose, respectively, and 3.1% for the placebo group.