Qsymia (phentermine hydrochloride; topiramate): NDA 22580

Contingent upon a category X pregnancy designation, Dr. Carlson recommends approval of the application.

Dr. Lau concludes that the clinical pharmacology data submitted in support of the application are acceptable and recommends approval.

The applicant's complete response included data from a phase 2 clinical study designed to examine the effect of Qsymia in patients with obstructive sleep apnea.

I agree with Dr. Roberts that Qsymia should be approved.

When asked if the overall benefit-risk assessment supported approval of Qsymia for the treatment of obesity in individuals with a BMI > 30 kg/m2 or > 27 kg/m2 when accompanied by a weight-related comorbidity, 20 committee members voted "yes" and two voted "no.

The data described herein reflects exposure to Qsymia in two, 1-year, randomized, double-blind, placebocontrolled, multicenter clinical trials, and two Phase 2 supportive trials in 2318 adult patients (936 [40.4%] patients with hypertension, 309 [13.3%] patients with type 2 diabetes, 808 [34.9%] patients with BMI greater than 40 kg/m2) exposed for a mean duration of 298 days.

In the 1-year controlled trials of Qsymia, the incidence of persistent treatment-emergent decreases in serum bicarbonate below the normal range (levels of less than 21 mEq/L at 2 consecutive visits or at the final visit) was 8.8% for Qsymia 3.75 mg/23 mg, 6.4% for Qsymia 7.5 mg/46 mg, and 12.8% for Qsymia 15 mg/92 mg, compared to 2.1% for placebo.

In Study 2, overweight and obese patients were randomized to receive 1 year of treatment with placebo (N=994), Qsymia 7.5 mg/46 mg (N=498), or Qsymia 15 mg/92 mg (N=995) in a 2:1:2 ratio.

The use of Qsymia can cause fetal harm and weight loss offers no clear clinical benefit to a pregnant patient (see Clinical Considerations).

A greater proportion of patients randomized to QSYMIA than placebo achieved 5%, 10%, and 15% BMI reduction.

The CRL identified teratogenicity, increases in heart rate, and the lack of an adequate risk evaluation and mitigation strategy (REMS) as deficiencies that needed to be adequately address before regulatory approval would be considered.

To summarize, within the framework of the approved REMS and labeling, I believe the currently-available data support approval of Qsymia for chronic weight management in patients with a BMI > 30 kg/m2 or > 27 kg/m2 when accompanied by a weight-related comorbidity.

Your proposed modifications to the REMS consist of changes to the REMS to align with updated labeling from prior approval supplement (S-021), which added a new indication for pediatric patients aged 12 years and older with BMI in the 95th percentile or greater for standardized age and sex.

• Known hypersensitivity or idiosyncrasy to the sympathomimetic amines [see Adverse Reactions (6.2)].

Antiepileptic drugs (AEDs), including topiramate, a component of Qsymia, increase the risk of suicidal thoughts or behavior in patients taking these drugs for any indication.

Antiepileptic drugs (AEDs), including topiramate, increase the risk of suicidal thoughts or behavior in patients taking these drugs for any indication.

We remind you that there are postmarketing requirements listed in the July 17, 2012, approval letter and the April 3, 2020, and June 7, 2021, postapproval postmarketing requirement letters that are still open.