FDA BRIEF: Week of Nov 7, 2016
VEMLIDY (tenofovir alafenamide) tablets
Gilead Sciences, Foster City, CA, USA
INDICATION: Treatment of chronic hepatitis B virus infection in adults with compensated liver disease
- Chronic hepatitis B is a life-threatening illness
- Affects up to 2.2 million people in the US
REG PATHWAY: SNDA (also marketed as Descovy)
MECHANISM OF ACTION: nucleoside analog reverse transcriptase inhibitor, inhibits HBV replication through incorporation into viral DNA by the HBV reverse transcriptase, which results in DNA chain-termination.
- 2 randomized, double-blind, active-controlled studies, 48-week data, N=425 and N=873, patients not allowed to receive other nucleosides, nucleotides, or interferon
- VEMLIDY vs Tenofovir Disoproxil Fumarate (Viread)
- Primary Endpoint: Proportion of subjects with plasma HBV DNA levels below 29 IU/mL at Week 48.
- Additional endpoints: Proportion of subjects with ALT normalization, HBsAg loss and seroconversion, and HBeAg loss and seroconversion
- Noninferior to Viread
- Boxed Warning: Risks of lactic acidosis/severe hepatomegaly with steatosis and post-treatment severe acute exacerbation of hepatitis B
- Commonly reported adverse events: Headache, abdominal pain, fatigue, cough, nausea and back pain
INDICATION: SELZENTRY is indicated in combination with other antiretroviral agents for the treatment of only CCR5 tropic human immunodeficiency virus type 1 (HIV 1) infection in patients 2 years of age and older weighing at least 10 kg.
- Open-label, multicenter trial, 2-<18 years old, infected with only CCR5 tropic HIV 1; dosing based on body sruface area and concomitant potent CYP3A inhibitors and/or inducers.
- At 48 weeks, 48% achieved plasma HIV-1 RNA less than 48 copies per mL; 65% achieved plasma HIV-1 RNA less than 400 copies per mL
- Mean CD4+ cell count (percent) increase from baseline to Week 48 was 247 cells per mm3 (5%).
- Safety profile through 96 weeks was similar to that for adults
- Point-of-care test – self-contained, disposable dipstick-format lateral flow test that includes an internal process Control Lin
- Ebola Zaire virus antigen, VP40 protein, present in the specimen, to bind nanoparticles labeled with antigen specific antibodies
- . As the specimen and nanoparticles flow across the device membrane, immobilized Ebola Zaire virus antigenspecific antibody absorbs the nanoparticle immune- to generate chromogenic signal
International, multi-center, open-label, randomized trial (n=240), OPDIVO vs Investigator’s Choice of chemotherapy, patients with recurrent or metastatic SCCHN with disease progression
- Primary Endpoint: Overall Survival (OS)
- Statistically significant and clinically meaningful improvement in OS : Hazard Ratio 0.7 [95% CI: 0.52, 0.92]; p=0.0101
- Estimated median OS: 7.5 mo, vs 5.1 mo.
- Serious adverse reactions occurred: Pneumonia, dyspnea, respiratory failure, respiratory tract infection, and sepsis.
- Most common adverse reactions: Cough and dyspnea