Evotaz (atazanavir/cobicistat) / Gilead, BMS - LARVOL DELTA

Clinical Evaluation of Drug-Drug Interactions Between Bictegravir and Strong Inhibitors/Inducers of the CYP3A4, UGT1A1, or P-gp Pathways. (PubMed, J Clin Pharmacol) - "The pharmacokinetics (PK) and safety of bictegravir (administered alone or as bictegravir/emtricitabine/tenofovir alafenamide fumarate [TAF]) were assessed when co-administered with inducers (rifampin, rifabutin, and rifapentine) or inhibitors (atazanavir ± cobicistat, darunavir + cobicistat, and voriconazole) of cytochrome P450 3A4 (CYP3A4), uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1), and/or P-glycoprotein (P-gp). Induction of CYP3A4 with/without UGT1A1 significantly influenced bictegravir PK, although Ctrough remained above the protein-adjusted 95% effective concentration. These findings should be considered when co-administering medications with bictegravir."

Journal • Human Immunodeficiency Virus • Infectious Disease • CYP3A4 • UGT1A1

Antiretroviral therapy in pregnancy in England in 2019‐2022: common regimens and treatment modifications (HIV-Glasgow 2024) - "Among pregnancies conceived on ART, most common (reported in >5%) first regimens were efavirenz (EFV) + tenofovir disoproxil fumarate (TDF) + emtricitabine (FTC) (13.5% [267/1974]), rilpivirine (RPV) +TDF+FTC (11.6% [228/1974]), darunavir/ritonavir (DRV/r) +TDF+FTC (8.0% [158/1974]), dolutegravir (DTG) + lamivudine (3TC) + abacavir (ABC) (7.7% [152/1974]), and raltegravir (RAL) +TDF+FTC (6.4% [127/1974]). Where ART was initiated during pregnancy (55.7% [234/420] diagnosed antenatally), median gestational age at start was 15 weeks (IQR 12–19); most common first regimens were RAL+TDF+FTC (17.7% [75/423]), DRV/r+TDF+FTC (15.4% [65/423]), atazanavir/ritonavir (ATV/r) +TDF+FTC (12.5% [53/423]), DTG+3TC+ABC (9.2% [39/423]) and DTG+TDF+FTC (8.3% [35/423])...3TC, lamivudine; ABC, abacavir; ATV/c, atazanavir/cobicistat; ATV/r, atazanavir/ritonavir; BIC, bictegravir; DRV/c, darunavir/cobicistat; DRV/r, darunavir/ritonavir; DTG, dolutegravir; EFV, efavirenz; EVG/c,..."

Human Immunodeficiency Virus • Infectious Disease

PRESTIGIO RING "a 59-year-old man with multidrug resistant HIV-1 infection failing a regimen including dolutegravir, rilpivirine, atazanavir/cobicistat: successful treatment tailoring based on genotypic and phenotypic resistance tests". (PubMed, New Microbiol) - "The salvage ART regimen, which included drugs with novel mechanisms of action (MoA), was tailored to the patient's clinical characteristics and on the resistance pattern explored with genotypic and phenotypic investigation, allowing the achievement of viro-immunological success. The use of recently approved drugs with novel MoA, combined with an optimized background regimen, may also achieve virological suppression in people with LTO."

Journal • Human Immunodeficiency Virus • Infectious Disease

Synthetic and Clinical Perspectives of EVOTAZ: An Overview. (PubMed, Mini Rev Med Chem) - "It is a once-daily (OD) fixed-dose combination of Cobicistat, a cytochrome P450 (CYP) enzyme inhibitor, and Atazanavir, a protease inhibitor. The drug is not effective in children under the age of 18; however, it is still being studied for various parameters. This review article focuses on EVOTAZ's preclinical and clinical aspects, as well as its efficacy and safety profiles."

Journal • Human Immunodeficiency Virus • Infectious Disease

A Combination of Novel HIV-1 Protease Inhibitor and Cytochrome P450 (CYP) Enzyme Inhibitor to Explore the Future Prospective of Antiviral Agents: Evotaz. (PubMed, Curr HIV Res) - "Evotaz is a combined once-daily fixed drug, containing Atazanavir, an HIV protease inhibitor, and cobicistat, an inhibitor of the human liver cytochrome P450 (CYP) enzyme. The medicine is still being studied for a number of criteria, but its usefulness in children under the age of 12 is currently unknown. The preclinical and clinical characteristics of Evotaz, as well as its safety and efficacy profiles and a comparison of the novel drug with antiviral medications presently available in the market, are the main topics of this review paper."

Journal • Human Immunodeficiency Virus • Infectious Disease

A Study to Compare the Drug Levels of Atazanavir and Cobicistat Between the Coadministration of Age-Appropriate Mini-Tablet Formulations and the Coadministration of the Individual Reference Products in Healthy Adults Under Fed Conditions (clinicaltrials.gov) - P1 | N=42 | Completed | Sponsor: Bristol-Myers Squibb | Not yet recruiting ➔ Completed

Trial completion

A Study to Compare the Drug Levels of Atazanavir and Cobicistat Between the Coadministration of Age-Appropriate Mini-Tablet Formulations and the Coadministration of the Individual Reference Products in Healthy Adults Under Fed Conditions (clinicaltrials.gov) - P1 | N=42 | Not yet recruiting | Sponsor: Bristol-Myers Squibb | Initiation date: Feb 2022 ➔ May 2022

Trial initiation date

A Study to Compare the Drug Levels of Atazanavir and Cobicistat Between the Coadministration of Age-Appropriate Mini-Tablet Formulations and the Coadministration of the Individual Reference Products in Healthy Adults Under Fed Conditions (clinicaltrials.gov) - P1 | N=42 | Not yet recruiting | Sponsor: Bristol-Myers Squibb

New P1 trial

Taste Properties of Atazanavir and Cobicistat (clinicaltrials.gov) - P1; N=6; Completed; Sponsor: Bristol-Myers Squibb; Active, not recruiting ➔ Completed; Trial completion date: Apr 2020 ➔ Sep 2021; Trial primary completion date: Apr 2020 ➔ Sep 2021

Clinical • Trial completion • Trial completion date • Trial primary completion date • Human Immunodeficiency Virus • Infectious Disease • Pediatrics

A Study to Examine the Acceptable Taste and to Estimate the Amount of Atazanavir and Cobicistat in the Body When Taken as a Combination Product Versus When Taken as Separate Products at the Same Time (clinicaltrials.gov) - P1; N=34; Completed; Sponsor: Bristol-Myers Squibb; Not yet recruiting ➔ Completed

Clinical • Trial completion

Pharmacokinetics of atazanavir boosted with cobicistat in pregnant and postpartum women with HIV. (PubMed, J Acquir Immune Defic Syndr) - "Standard atazanavir/cobicistat dosing during pregnancy results in lower exposure which may increase the risk of virologic failure and perinatal transmission."

Clinical • Journal • PK/PD data • Human Immunodeficiency Virus • Infectious Disease

Pharmacokinetic Study of Antiretroviral Drugs and Related Drugs During and After Pregnancy (clinicaltrials.gov) - P=N/A; N=1578; Completed; Sponsor: National Institute of Allergy and Infectious Diseases (NIAID); Phase classification: P4 ➔ P=N/A

Phase classification • Human Immunodeficiency Virus • Infectious Disease

Physiologically based pharmacokinetic modelling to support the clinical management of drug-drug interactions with bictegravir. (PubMed, Clin Pharmacol Ther) - "Clinically observed DDI data for bictegravir co-administered with voriconazole, darunavir/cobicistat, atazanavir/cobicistat, and rifampicin were predicted within the 95% confidence interval of the PBPK model simulations...Generally, our simulation results suggest that bictegravir should not be co-administered with strong CYP3A and UGT1A1 inhibitors and inducers (e.g. atazanavir, nilotinib, and rifampicin), but based on the present modelling results, bictegravir could be administered with moderate dual perpetrators (e.g. efavirenz). Importantly, the inducing effect of rifampicin on bictegravir was predicted to be reversed with the concomitant administration of a strong inhibitor such as ritonavir, resulting in a DDI magnitude within the efficacy and safety margin for bictegravir (0.5-2.4-fold). In conclusion, the PBPK modelling strategy can effectively be used to guide the clinical management of DDIs for novel drugs with limited clinical experience, such as bictegravir."

Clinical • Journal • PK/PD data • Human Immunodeficiency Virus • Infectious Disease • UGT1A1

Pharmacokinetic Study of Antiretroviral Drugs and Related Drugs During and After Pregnancy (clinicaltrials.gov) - P4; N=1578; Completed; Sponsor: National Institute of Allergy and Infectious Diseases (NIAID); Active, not recruiting ➔ Completed

Trial completion • Human Immunodeficiency Virus • Infectious Disease

Confirmation of the drug-drug interaction potential between cobicistat-boosted antiretroviral regimens and hormonal contraceptives. (PubMed, Antivir Ther) - "Consistent with COBI-mediated CYP3A inhibition, drospirenone exposure increased following coadministration with COBI-containing regimens, with a greater increase with ATV+COBI. Thus, clinical monitoring for drospirenone-associated hyperkalemia is recommended with DRV+COBI and ATV+COBI should not be used with drospirenone. Lower EE exposure with DRV+COBI may be attributed to inductive effects of DRV on CYP enzymes and/or intestinal efflux transporters (ie, P-gp) involved in EE disposition."

Journal • Human Immunodeficiency Virus • Infectious Disease

Open-Label Study to Evaluate Switching From a TDF-Containing Combination Regimen to a TAF-Containing Combination Single Tablet Regimen (STR) in Virologically-Suppressed, HIV-1 Positive Subjects (clinicaltrials.gov) - P3; N=1500; Active, not recruiting; Sponsor: Gilead Sciences; Trial primary completion date: Oct 2014 ->Mar 2015

Trial primary completion date • Biosimilar • Chronic Kidney Disease • Human Immunodeficiency Virus • Immunology • Inflammation

A Study to Estimate the Bioavailability of Atazanavir and Cobicistat in a Fixed-dose Combination Formulation Compared with Coadministration in Individual Formulations and to Assess Palatability/Acceptability in Healthy Adults (clinicaltrialsregister.eu) - P1; N=34; Sponsor: Bristol-Myers Squibb International Corporation

Clinical • New P1 trial • Gene Therapies • Human Immunodeficiency Virus • Infectious Disease • Pediatrics

Study to Evaluate Efficacy and Safety of Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (D/C/F/TAF) Regimen Versus Boosted Protease Inhibitor (bPI) Along With Emtricitabine/Tenofovir Disoproxil Fumarate (FTC/TDF) Regimen in... (clinicaltrials.gov) - P3; N=1146; Active, not recruiting; Sponsor: Janssen R&D Ireland; Recruiting ➔ Active, not recruiting

Enrollment closed • Biosimilar • Gene Therapies • Human Immunodeficiency Virus • Immunology • Small Cell Lung Cancer

Pharmacokinetic Study of Antiretroviral Drugs and Related Drugs During and After Pregnancy (clinicaltrials.gov) - P4; N=1786; Recruiting; Sponsor: National Institute of Allergy and Infectious Diseases (NIAID); Trial primary completion date: Jun 2019 ➔ Mar 2018

Trial primary completion date • Biosimilar • Gene Therapies • Human Immunodeficiency Virus • Immunology

DATE-4: A Drug-drug Interaction Study Between Daclatasvir and Atazanavir/Ritonavir or Atazanavir/Cobicistat (clinicaltrials.gov) - P1; N=16; Not yet recruiting; Sponsor: Radboud University

New P1 trial • Biosimilar • Hepatitis C Virus • Immunology • Inflammation

Drug updates and approvals. (PubMed) - Nurse Pract - "This article highlights important prescribing information for some interesting new drugs approved by the FDA within the past year. These include: Atazanavir and cobicistat (Evotaz), Ceftazidime and avibactam (Avycaz), Edoxaban (Savaysa), Ivabradine (Corlanor), Liraglutide (rDNA origin) injection (Saxenda), Perindopril arginine/amlodipine besylate (Prestalia), Secukinumab (Cosentyx) subcutaneous injection."

Journal • Biosimilar

Cobicistat-containing antiretroviral regimens are not recommended during pregnancy: viewpoint. (PubMed, AIDS) - ": Product labels for cobicistat with atazanavir or darunavir, and for elvitegravir/cobicistat/emtricitabine/tenofovir (alafenamide or disoproxil fumarate) were recently updated to state that these products are not recommended for initiation during pregnancy, and an alternative regimen is recommended for those who become pregnant during therapy with these products. In the absence of data with atazanavir/cobicistat, we leveraged the available data with darunavir/cobicistat and elvitegravir/cobicistat to make recommendations for atazanavir/cobicistat. Darunavir/ritonavir and atazanavir/ritonavir remain viable treatment options for pregnant women."

Journal

Population pharmacokinetic analysis of elvitegravir and cobicistat in HIV-1-infected individuals. (PubMed) - "Elvitegravir and cobicistat pharmacokinetic variability appears to be mainly explained by drug-drug interactions that may be encountered in routine clinical practice. In these cases, therapeutic drug monitoring and surveillance for potential toxicities would be justified."

Journal • Biosimilar • Gene Therapies

Pharmacokinetic Effect of Evotaz/Microgynon Co-administration (clinicaltrials.gov) - P1; N=13; Terminated; Sponsor: St Stephens Aids Trust; N=30 ➔ 13; Recruiting ➔ Terminated; Insufficient enrolment and "business reasons"

Enrollment change • Trial termination • Biosimilar • Gene Therapies • Human Immunodeficiency Virus • Infectious Disease • Long-acting Reversible Contraceptives • Women's Health

Taste Properties of Atazanavir and Cobicistat (clinicaltrials.gov) - P1; N=4; Not yet recruiting; Sponsor: Bristol-Myers Squibb

New P1 trial • Biosimilar • Hematological Malignancies • Human Immunodeficiency Virus