SYMTUZA®

Study Design/Efficacy

DIAMOND STUDY

Phase 3, open-label, single-arm, prospective, multicenter* study1

In this rapid-initiation trial, treatment began before resistance test results were available.1

Primary endpoint: Proportion of patients with VL <50 copies/mL at 48 weeks (ITT/FDA Snapshot)1

Secondary endpoint: Proportion of patients with VL <50 copies/mL at 48 weeks (observed analysis)1

DIAMOND was not a pivotal registration trial.

Prior to or when initiating SYMTUZA®, patients should undergo testing for HBV and renal function. Appropriate labs, including liver testing, hepatitis serology, and HIV genotypic resistance testing should be conducted and patients monitored during treatment as clinically appropriate.1

* Study was conducted at 16 sites located in Arizona, California, District of Columbia, Florida, Georgia, Illinois, New Jersey, New Mexico, and Texas.2

Evaluations could be done sooner based on the availability of results. Patients not meeting pre-defined safety or resistance stopping rules continued treatment.1

Screening/baseline safety laboratory findings were evaluated with the following stopping criteria (retesting of abnormal screening/baseline safety laboratory values was allowed once): 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, or 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.

§ 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 M184V mutation alone.

Study Demographics1

Patient Characteristics1

Study Included

21% of patients with CD4+ cell count <200 cells/mm3

25% of patients with viral loads100,000 copies/mL

High Virologic Response Rates Achieved with SYMTUZA® at Week 48

  • Virologic failure: 8% of patients had 50 copies/mL (ITT/FDA Snapshot)1
  • 7% had no VL data (ITT/FDA snapshot)1
96%

of Patients Treated With SYMTUZA® Had Undetectable VLs (<50 copies/mL)1 (observed analysis)

  • No patients discontinued due to lack of efficacy or protocol-defined virologic failure

DHHS guidelines recommend SYMTUZA® in RAPID INITIATION3

*Observed=Patients with missing data were excluded from the analysis.

Safety & Tolerability Profile

Among patients treated with SYMTUZA® over 48 weeks1

<1% Discontinuation Rate Due to Adverse Events

No patients discontinued treatment due to diarrhea

  • Grade 3-4 laboratory abnormalities occurring in 2% of patients included increases in AST (5%), ALT (3%), and bilirubin (3%).

Most common adverse reactions at 48 weeks1

ADVERSE REACTIONS (>2%) GRADE >2 ALL GRADES
Diarrhea (%) 2 12
Nausea (%) 2 12
Rash* (%)     4 5
Vomiting (%) 0 4
Fatigue (%) 0 3

* Pooled preferred terms of dermatitis, allergic dermatitis, rash, macular rash, maculo-papular rash, papular rash, and pruritic rash.1

All rash AEs were Grade 1 or 2, except for 1 that was Grade 3.

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

  • Most adverse events during treatment with SYMTUZA® were mild to moderate in severity (Grade 1 or Grade 2)
    • One patient discontinued due to allergic dermatitis (Grade 3), pyrexia (Grade 2) and lip swelling (Grade 2). All adverse reactions resolved after discontinuation of study treatment
    • No patients discontinued treatment due to central nervous system, renal, or bone adverse reactions
  • 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.

ALT=alanine aminotransferase; ARV=antiretroviral; AST=aspartate aminotransferase; DHHS=Department of Health and Human Services; eGFR=estimated glomerular filtration rate; FTC/TDF=emtricitabine/tenofovir disoproxil fumarate; HBV=hepatitis B virus; ITT=intent-to-treat; MDRD=Modification of Diet in Renal Disease; PrEP=pre-exposure prophylaxis; RAMs=resistance-associated mutations; ULN=upper limit of normal; VL=viral load.

References: 1. Huhn G, Crofoot G, Ramgopal M, et al. Darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) rapid initiation for HIV-1 infection: primary analysis of the DIAMOND study. Poster presented at: 13th Annual American Conference for the Treatment of HIV (ACTHIV); April 11-13, 2019; Miami, Florida. 2. NIH U.S. National Library of Medicine. A study to evaluate the efficacy and safety of D/C/F/TAF once daily fixed dose combination (FDC) regimen in newly diagnosed, antiretroviral treatment-naïve human immunodeficiency virus type 1 (HIV-1) infected participants receiving care in a test and treat model of care. https://clinicaltrials.gov/ct2/show/NCT03227861. Accessed January 18, 2019. 3. Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in adults and adolescents living with HIV. Department of Health and Human Services. http://www.aidsinfo.nih.gov/ContentFiles/AdultandAdolescentGL.pdf. Accessed January 18, 2019.