Emtricitabin / Tenofoviralafenamid (1) – Descovy®

• Clinical trials
  • The GS-US-292-0109 study is an open-label, actively controlled, randomised trial involving patients who had previously received antiretroviral therapy.

a) Adults not previously treated with antiretrovirals (treatment-naive)

• For adults not previously treated with antiretrovirals, an additional benefit is not proven compared with the appropriate comparator therapy.
• No relevant data were presented for the patient population of adults not previously treated with antiretrovirals (treatment-naive) to assess the additional benefit of FTC/TAF compared with the appropriate comparator therapy.

b) Adolescents aged 12 years and over who have not previously received antiretroviral therapy (treatment-naive)

• For antiretroviral-naïve adolescents aged 12 years and over, an additional benefit over the appropriate comparator therapy is not proven.
• For the patient population of antiretroviral-naive adolescents aged 12 years and over, a single-arm, uncontrolled study (GS-US-292-0106) was submitted. Due to the study design (single-arm study design, no appropriate comparator therapy) and the resulting minor statistical power, no conclusions regarding additional benefit can be drawn.

c) Adults who have previously received antiretroviral therapy (treatment-experienced)

• An additional benefit is not proven for antiretrovirally pre-treated (treatment-experienced) adults.
• The assessment of additional benefit is therefore carried out for the overall population of treatment-experienced adults. As the statistically significant results therefore apply only to a subgroup of this patient group, the relevance of which to the everyday healthcare situation is questionable, no additional benefit or less benefit of FTC/TAF compared with the appropriate comparator therapy can be inferred for the overall population from the data on side effects.
• mortality
  • For the endpoint of all-cause mortality, the result of the meta-analysis was not statistically significant. Additional benefit or greater harm from FTC/TAF compared with FTC/TDF is not proven for this endpoint.
• Morbidity – AIDS-defining events
  • The endpoint ‘AIDS-defining events’ (CDC Class C events) consists mainly of opportunistic infections (e.g. pneumonia) and typical tumours (e.g. Kaposi’s sarcoma, lymphomas), which indicate the onset of AIDS.
  • For the endpoint ‘AIDS-defining events’, the meta-analysis shows no statistically significant difference between the treatment groups.
• Morbidity – Virological response
  • The validated surrogate parameter ‘virological response (viral load)’ is also clinically relevant.
  • For virological response, the meta-analysis shows no significant difference between the treatment groups.
• Morbidity – CD4 cell counts
  • For CD4 cell counts, the meta-analysis shows no statistically significant difference between the treatment arms.
• Morbidity – Health status (EQ-5D VAS)
  • For the health status endpoint, the meta-analysis showed no statistically significant difference between the treatment groups.
• Health-related quality of life – SF-36 – physical summary score
  • The meta-analysis showed no statistically significant difference between the treatment groups in terms of the SF-36 physical total score.
• Health-related quality of life – SF-36 – mental health summary score
  • For the SF-36 mental health summary score, the study GS-US-311-1089 showed no statistically significant difference between the treatment groups, whilst the study GS-US-292-0109 showed a significant difference in favour of FTC/TAF.
  • As the 95% confidence interval does not lie entirely above the non-significance threshold of 0.2, the effect is assessed as not clinically relevant.
• Side effects – discontinuation due to AEs
  • For the endpoint ‘discontinuation due to AEs’, the studies GS-US-292-0109 and GS-US-311-1089 were analysed separately at the 48-week assessment point.
  • For the endpoint ‘discontinuation due to AEs’, a statistically significant difference in favour of FTC/TAF was observed in the STB stratum of study GS-US-292-0109. In study GS-US-311-1089, however, no statistically significant difference was observed between the treatment groups for this endpoint.
• Side effects – nervous system disorders
  • For the endpoint ‘nervous system disorders’, the meta-analysis shows a statistically significant difference to the detriment of FTC/TAF.
• Side effects – serious adverse events, severe AEs (Grade 3–4), psychiatric disorders, disorders of the skin and subcutaneous tissue, disorders of the gastrointestinal tract, disorders of the kidneys and urinary tract, bone fractures
  • For the above-mentioned endpoints, the meta-analysis revealed no statistically significant differences between the treatment groups.
  • For the endpoint ‘psychiatric disorders’, the GS-US-292-0109 study did show a statistically significant difference in favour of FTC/TAF at 96 weeks; however, due to the open-label study design, this result must be regarded as potentially highly biased.
  • The endpoint ‘kidney and urinary tract disorders’ is not considered separately by the pharmaceutical manufacturer, but is listed as a component of the endpoint ‘kidney disorders’ together with surrogate parameters.
  • For the endpoint ‘bone fractures’, the results are not summarised meta-analytically due to differences in operationalisation. At the individual study level, there is no statistically significant difference between the treatment groups.
• Conclusion
  • Overall, no data are available for patients with an indication for switching. For patients without an indication for switching, a meta-analytical examination of the 48-week data in the ‘side effects’ category reveals a statistically significant difference to the detriment of FTC/TAF for the endpoint ‘disorders of the nervous system’.
  • In summary, for pre-treated, HIV-1-infected adult patients, an overall assessment of the results regarding mortality, morbidity, quality of life and side effects reveals no additional benefit of FTC/TAF compared with the appropriate comparator therapy.
  • It is questionable whether this treatment situation reflects standard clinical practice. No additional benefit of FTC/TAF over the appropriate comparator therapy can be inferred from the results.

d) antiretrovirally pre-treated (treatment-experienced) adolescents aged 12 years and over

• No additional benefit is proven for antiretrovirally pre-treated (treatment-experienced) adolescents aged 12 years and over.
• Compared with the appropriate comparator therapy – an individualised antiretroviral regimen based on prior therapy(ies) and taking into account the reason for the change in treatment, in particular treatment failure due to virological failure and any associated development of resistance, or due to side effects, no data are available for emtricitabine/tenofovir alafenamide in antiretrovirally pre-treated, HIV-1-infected adolescents aged 12 years and over.

Courtesy translation only, please refer to the German original.