Formulated for Improved Tolerability

SYMTUZA™ Safety and Tolerability Profile

<2% discontinuation rate due to treatment-related adverse events
among 1125 patients treated with SYMTUZA™ over 48 weeks1

SYMTUZA HIV Treatment Discontinuation Rates
  • Through 48 weeks, only 1 treatment-naïve patient (0.3%) and 1 virologically suppressed patient (0.1%) discontinued SYMTUZA™ due to diarrhea3,4

Grades of adverse reactions: Grade 1=mild, Grade 2=moderate, Grade 3=severe, Grade 4=life-threatening or disabling.

*Control: DRV/c + FTC/TDF.
Control: bPI + FTC/TDF.

 

AMBER Adverse reactions in treatment-naïve patients over 48 weeks1

 

Symtuza adverse reactions
  • Most adverse reactions during treatment with SYMTUZA™ were mild to moderate in severity
    • One Grade 3 reaction was reported and no Grade 4 adverse reactions were reported during treatment with SYMTUZA™
  • Few treatment-naïve patients started a lipid-lowering medication:
    • 1.7% (n=6) of patients in the SYMTUZA™ arm and 0.6% (n=2) in the control arm started a lipid-lowering drug during treatment
  • Overall, the safety profile of SYMTUZA™ in virologically suppressed adults was similar to that in subjects with no prior antiretroviral treatment history
  • This is not a complete list of all adverse drug reactions reported with the use of SYMTUZA™. Please refer to the full Prescribing Information for a complete list of adverse drug reactions

 

DIAMOND: Safety and Tolerability at Week 24 (Interim Analysis)5

 

Patients in study

of patients continued in the study

  • 3 patients discontinued due to safety stopping rules
  • 3 were lost to follow up
  • 2 withdrew consent
  • 1 due to a protocol violation
  • 1 due to adverse events (AEs)
  • No patients met resistance stopping rules
Treatment Adverse Events

of patients discontinued due to treatment-related adverse events among 109 patients

  • One patient discontinued due to AEs; this patient had allergic dermatitis (Grade 3), pyrexia (Grade 2), and lip swelling (Grade 2), and all AEs resolved after discontinuation of study treatment
  • There were no discontinuations due to central nervous system, gastrointestinal, renal, or bone AEs
  • There were no cases of immune reconstitution inflammatory events

Most common adverse reactions in a rapid initiation scenario at Week 24 (N=109)5

  • Most adverse events during treatment with SYMTUZA™ were mild to moderate in severity
    • Only 2 Grade 3 AEs related to study drug were reported and there were no Grade 4 AEs observed
  • One Grade 3-4 laboratory abnormality occurred in ≥2% of patients (increased AST in 4% [4] of patients)

Pooled preferred terms of dermatitis, allergic dermatitis, rash, macular rash, maculo-papular rash, papular rash, and pruritic rash.

Safety and Resistance Stopping Rules

Patients not meeting predefined safety or resistance stopping rules continued treatment

Stopping criteria used to evaluate baseline labs:

  • eGFR (MDRD formula) <50 mL/min
  • AST or ALT ≥2.5 times the ULN
  • Serum lipase ≥1.5 times the ULN
  • Positive pregnancy test for women of childbearing potential
  • Laboratory results that the investigator believes should result in discontinuation of study medication
  • Active hepatitis C infection that required immediate treatment or is expected to require treatment during the study with agents not compatible with SYMTUZA™

Stopping rule findings:

  • Investigators reviewed screening/baseline laboratory findings as results became available
  • 5 patients met safety stopping rule criteria; all had confirmed evidence of AST or ALT elevations ≥2.5 times the ULN at the screening/baseline visit
    • 3 of these patients discontinued according to the protocol and the other 2 patients remained in the study based on clinical assessment by the investigator and agreement of the sponsor

Criteria used to evaluate baseline resistance:

  • Resistance was evaluated based on predicted genotypic sensitivity (there was no exclusion based on the presence of specific RAMs). Patients who did not show full genotypic sensitivity to the components of SYMTUZA™ (assessed using GenoSure Prime®) were stopped; an exception was resistance to lamivudine/emtricitabine associated with the M184I or V mutation alone
AST= aspartate amino transferase; ALT=alanine aminotransferase; bPI=boosted protease inhibitor; DRV/c=darunavir/cobicistat; eGFR=estimated glomerular filtration rate; FTC=emtricitabine; MDRD=Modification of Diet in Renal Disease; TDF=tenofovir disoproxil fumarate; ULN=upper limit of normal.

References: 1. SYMTUZA™ [package insert]. Titusville, NJ: Janssen Therapeutics, Division of Janssen Products, LP. 2. Orkin C, Molina JM, Negredo E, et al. Efficacy and safety of switching from boosted protease inhibitors plus emtricitabine and tenofovir disoproxil fumarate regimens to single-tablet darunavir, cobicistat, emtricitabine, and tenofovir alafenamide at 48 weeks in adults with virologically suppressed HIV-1 (EMERALD): a phase 3, randomised, non-inferiority trial. Lancet HIV. 2018;5(1):e23-e34. 3. Eron JJ, Orkin C, Gallant J, et al. A week-48 randomized phase-3 trial of darunavir/cobicistat/emtricitabine/tenofovir alafenamide in treatment-naïve HIV-1 patients. AIDS. 2018;32:1431-1442. 4. Data on file. Janssen Therapeutics, Division of Janssen Products, LP. 5. Huhn GD, Crofoot G, Ramgopal M, et al. Darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) in a test-and-treat model of care for HIV-1 infection: interim analysis of the DIAMOND study. Poster presented at the 22nd International AIDS Conference; July 23-27, 2018; Amsterdam, The Netherlands.