February 4, 2020
The VEMLIDY (tenofovir alafenamide) label was updated to include the Week 48 safety and efficacy data from Study GS-US-320-4018, a study in virologically suppressed adults with chronic hepatis B virus infection who switched from tenofovir disoproxil fumarate 300 mg once daily (QD) to tenofovir alafenamide 25 mg QD. In addition, updates to the pregnancy section were made. A summary of the changes is provided below:
Section 6: ADVERSE REACTIONS
6.1 Clinical Trials Experience
Adverse Reactions in Virologically Suppressed Adult Subjects with Chronic Hepatitis B
The safety of VEMLIDY in virologically suppressed adults is based on Week 48 data from a randomized, double-blind, active-controlled trial (Trial 4018) in which subjects taking TDF at baseline were randomized to switch to VEMLIDY (N=243) or to continue their TDF treatment (N=245). Adverse reactions observed with VEMLIDY in Trial 4018 were similar to those in Trials 108 and 110.
Renal Laboratory Tests, Bone Mineral Density Effects, and Serum Lipids
In virologically suppressed adults in Trial 4018, changes from baseline in renal function, BMD, and lipid parameters in the VEMLIDY and TDF groups at Week 48 were similar to those observed in Trials 108 and 110 at Week 96.
Section 8: USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
Risk Summary
Available data from the APR show no significant difference in the overall risk of birth defects for tenofovir alafenamide (TAF) compared with the background rate for major birth defects of 2.7% in the U.S. reference population of the Metropolitan Atlanta Congenital Defects Program (MACDP) (see Data). The rate of miscarriage is not reported in the APR. The estimated background rate of miscarriage in clinically recognized pregnancies in the U.S. general population is 15% to 20%.
Data
Human Data
Based on prospective reports to the APR of exposures to TAF-containing regimens during pregnancy resulting in live births (including over 200 exposed in the first trimester and over 80 exposed in the second/third trimester), the prevalence of birth defects in live births was 5.2% (95% CI: 2.7% to 8.8%) and 1.2% (95% CI: 0% to 6.5%) following first and second/third trimester exposure, respectively, to TAF-containing regimens. Methodologic limitations of the APR include the use of MACDP as the external comparator group. The MACDP population is not disease-specific, evaluates women and infants from a limited geographic area, and does not include outcomes for births that occurred at <20 div="" gestation.="" weeks="">
Section 14: CLINICAL STUDIES
14.3 Clinical Trials in Virologically Suppressed Adults with Chronic Hepatitis B Virus Infection Who Switched to VEMLIDY
The efficacy and safety of switching from TDF to VEMLIDY in virologically suppressed adults with chronic hepatitis B virus infection is based on 48-week data from a randomized, double-blind, active-controlled trial, Trial 4018 (N=488). Subjects must have been taking TDF 300 mg once daily for at least 12 months, with HBV DNA less than the Lower Limit of Quantitation by local laboratory assessment for at least 12 weeks prior to screening and HBV DNA <20 14="" 16="" 1:1="" 220="" 224="" 25="" 27="" 300="" 51="" 68="" 71="" 82="" a="" age="" alt="" and="" asian="" at="" baseline="" by="" cirrhosis.="" daily="" div="" duration="" eag-positive="" either="" groups="" had="" hbeag-negative="" hbeag="" history="" in="" iu="" male="" mean="" median="" mg="" ml="" negative.="" of="" on="" once="" or="" patients="" prior="" randomized="" ratio="" respectively.="" screening.="" serum="" status="" stay="" stratified="" subjects="" switch="" tdf="" the="" to="" treatment="" u="" vemlidy="" was="" weeks="" were="" white="" years="">
The primary efficacy endpoint was the proportion of subjects with plasma HBV DNA levels ≥20 IU/mL at Week 48. Additional efficacy endpoints in Trial 4018 included the proportion of subjects with HBV DNA <20 alt="" and="" div="" hbeag="" hbsag="" iu="" loss="" ml="" normal="" normalization="" seroconversion.="" seroconversion="">
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