FDA Approved Changes to the Genvoya Label

Today, FDA approved changes to the Genvoya (elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide) package insert to update the 144 week data from a trial in HIV-1 positive patients with mild to moderate renal impairment. Addition of drug interaction data was also included. The specific changes are as follows

Section 2: DOSAGE AND ADMINISTRATION

• 2.1 Testing Prior to Initiation and During Treatment with GENVOYA:

Prior to and during treatment, as clinically appropriate, assess serum creatinine, estimated creatinine clearance, urine glucose and urine protein in all patients, and also assess serum phosphorus in patients with chronic kidney disease

Section 6: ADVERSE REACTIONS

• Clinical Trials in Adult Subjects with Renal Impairment
  In an open-label trial (Study 112), 248 HIV-1 infected subjects with eGFR of 30 to 69 mL per minute (by Cockcroft-Gault method) were treated with GENVOYA for a median duration of 144 weeks. Of these subjects, 65% had previously been on a stable TDF-containing regimen. A total of 5 subjects permanently discontinued GENVOYA due to the development of renal adverse events through Week 96. Three of these five were among the 80 subjects with baseline eGFRs of < 50mL/min and two subjects were among the 162 subjects with baseline eGFRs of ≥ 50mL/min. There were no further renal discontinuations between Weeks 96 and 144. Overall, renally impaired subjects receiving GENVOYA in this study had a mean serum creatinine of 1.5 mg/dL at baseline and 1.4 mg/dL at Week 144. Otherwise, the safety profile of GENVOYA in subjects in this study was similar to that of subjects with normal renal function

Section 7: DRUG INTERACTIONS

• Drospirenone/ethinyl estradiol was added with a clinical comment to state: plasma concentrations of drospirenone may be increased when coadministered with cobicistat-containing products. Clinical monitoring is recommended due to the potential for hyperkalemia.
• Atorvastatin was added with a clinical comment to state: Initiate with the lowest starting dose of atorvastatin and titrate carefully while monitoring for safety
• Voxilaprevir was added to the list of drugs without clinically significant interactions with Genvoya

Section 14: CLINICAL STUDIES

• 14.4       Clinical Trial Results in HIV-1 Infected Subjects with Renal Impairment

In Study 112, the efficacy and safety of GENVOYA once daily were evaluated in an open-label clinical trial of 248 HIV-1 infected subjects with renal impairment (eGFR of 30 to 69 mL per minute by Cockcroft-Gault method). Of the 248 enrolled, 6 were treatment-naïve and 242 were virologically suppressed (HIV-1 RNA less than 50 copies per mL) for at least 6 months before switching to GENVOYA.

 

The mean age was 58 years (range 24–82), with 63 subjects (26%) who were 65 years of age or older. Seventy-nine percent were male, 63% were White, 18% were Black, and 14% were Asian. Thirteen percent of subjects identified as Hispanic/Latino. The mean baseline CD4+ cell count was 664 cells per mm³ (range 126–1813). At Week 144,  81% (197/242 virologically suppressed subjects) maintained HIV-1 RNA less than 50 copies per mL after switching to GENVOYA. All six treatment-naïve subjects were virologically suppressed at Week 144. Five subjects among the entire study population had virologic failure at Week 144.

The updated label will soon be available at drugs@fda or DailyMed

 

Steve Morin

Office of Health and Constituent Affairs
Food and Drug Administration

 

Kimberly Struble
Division of Antiviral Products
Food and Drug Administration

 

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