Tybost (cobicistat) / Gilead - LARVOL DELTA

Towards human cardiac new approach methodologies (NAMs) to evaluate the combination of repolarization prolonging and shortening drugs: a pilot study. (PubMed, Front Drug Discov (Lausanne)) - "We conclude that cobicistat can attenuate moxifloxacin induced FPDcF prolongation at clinically relevant concentrations in vitro. Taken together, this work provides a foundation to evaluate drug combinations in vitro to aid regulatory decision-making and reduce the dependence on animal studies."

Journal • Cardiovascular

Feasibility of CSF and Plasma ctDNA in BRAF-altered Glioma During Treatment With Plixorafenib (clinicaltrials.gov) - P1 | N=15 | Recruiting | Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: May 2026 ➔ Jun 2027 | Trial primary completion date: Dec 2025 ➔ Jun 2026

Circulating tumor DNA • Trial completion date • Trial primary completion date • Brain Cancer • Glioma • Oncology • Sarcoma • Solid Tumor • BRAF

In silico screening of potential FGF2 inhibitors for cancer therapy. (PubMed, In Silico Pharmacol) - "Molecular docking study showed Elbasvir (1) to exhibit the strongest binding affinity (-8.1 kcal/mol), followed by Velpatasvir (2) (-7.6 kcal/mol), Daclatasvir (3) (-7.5 kcal/mol), Ritonavir (4) (-6.2 kcal/mol), Paliperidone Palmitate (5) (-5.9 kcal/mol), Saralasin (6) (-5.4 kcal/mol), Nystatin (8) (-5.2 kcal/mol), and Cobicistat (-5.1 kcal/mol)...Overall, the study provides mechanistic insights into the molecular interactions between FGF2 and these candidate drugs, highlighting the promising potential of compounds 1-6 and 8 for subsequent in vitro validation in cancer therapeutics. The online version contains supplementary material available at 10.1007/s40203-025-00495-2."

Journal • Acute Myelogenous Leukemia • Brain Cancer • Breast Cancer • Gastric Cancer • Glioblastoma • Hematological Malignancies • Leukemia • Lung Cancer • Nasopharyngeal Carcinoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • FGF2 • FGFR

Mitigating subtherapeutic cabozantinib exposure after prior mitotane therapy in adrenocortical carcinoma: Pharmacological boosting with cobicistat. (PubMed, Br J Clin Pharmacol) - "Our findings suggest that an aggressive approach, combining pharmacokinetic boosting, dose escalation and frequent pharmacokinetic monitoring is required to prevent undertreatment and toxicity. By mitigating mitotane-induced subtherapeutic concentrations, this pharmacokinetic strategy may facilitate more effective use and earlier initiation of cabozantinib as second-line treatment in ACC."

Journal • Adrenal Cortex Carcinoma • Genito-urinary Cancer • Oncology • Solid Tumor

Feasibility of CSF and plasma ctDNA in BRAF-altered glioma during treatment with plixorafenib: trial in progress (SNO 2025) - "Patients aged 18 years or older with measurable recurrent BRAF-V600 mutant glioma (by RANO 2.0), who have received prior BRAF and/or MEK inhibitor therapy (excluding tovorafenib) are eligible to be screened and consented for the study prior to surgery...Patients will initiate the study drug (oral plixorafenib 900mg daily with cobicistat 150mg daily) when clinically recovered from surgery...MRI, CSF, and plasma assessments will occur approximately every two months to evaluate disease status. The study is open and one participant has been successfully enrolled."

Circulating tumor DNA • Brain Cancer • Glioma • Solid Tumor • BRAF

Feasibility of CSF and plasma ctDNA in BRAF-altered glioma during treatment with plixorafenib: trial in progress (WFNOS 2025) - "Patients aged 18 years or older with measurable recurrent BRAF-V600 mutant glioma (by RANO 2.0), who have received prior BRAF and/or MEK inhibitor therapy (excluding tovorafenib) are eligible to be screened and consented for the study prior to surgery...Patients will initiate the study drug (oral plixorafenib 900mg daily with cobicistat 150mg daily) when clinically recovered from surgery...MRI, CSF, and plasma assessments will occur approximately every two months to evaluate disease status. The study is open and one participant has been successfully enrolled."

Circulating tumor DNA • Brain Cancer • Solid Tumor • BRAF

Beyond General HIV Risk: Insights on Antiretroviral Agents, Immune Status, and Cardiovascular Disease Progression in a Vulnerable Urban Cohort (AHA 2025) - "After adjustment, tenofovir use was associated with decreased CAD progression (aOR 0.14, 95% CI 0.03–0.69, p<0.05), while raltegravir (aOR 49.40, CI 1.84–1326.57, p<0.05), cobicistat (aOR 23.57, CI 1.31–425.58, p<0.05), cocaine use (aOR 13.52, CI 2.09–87.60, p<0.01), male sex (aOR 8.55, CI 1.24–59.12, p<0.05), and obstructive sleep apnea (aOR 25.23, CI 2.15–296.64, p<0.05) were associated with increased risk. Specific ART agents and CD4 count were independently associated with distinct CVD outcomes alongside traditional cardiovascular risk factors in this cohort. These insights support considering individual ART and immune status for tailored CVD risk assessment in vulnerable populations with HIV."

Cardiovascular • Coronary Artery Disease • Human Immunodeficiency Virus • Infectious Disease • Myocardial Infarction • Obstructive Sleep Apnea • Respiratory Diseases • Sleep Disorder • CD4

ProSTAR: A Study Evaluating CPI-1205 in Patients With Metastatic Castration Resistant Prostate Cancer (clinicaltrials.gov) - P1/2 | N=175 | Completed | Sponsor: Constellation Pharmaceuticals | Phase classification: P1b/2 ➔ P1/2 | Active, not recruiting ➔ Completed

Phase classification • Trial completion • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Adenocarcinoma • Prostate Cancer • Solid Tumor

Personalized osimertinib dose frequency adjustment and pharmacokinetic boosting to improve cost-effectiveness in advanced epidermal growth factor receptor (EGFR) mutated non-small cell lung cancer (NSCLC) treatment: OSIBOOST-2A study (ESMO 2025) - P4 | "Therefore, we investigate the feasibility of personalized Osi dose frequency reduction, with or without pharmacokinetic (PK) boosting (using the strong CYP3A inhibitor cobicistat) as a novel strategy to improve cost-effectiveness. Preliminary findings suggest that substantial cost reductions are achievable. Updated results will be presented."

Cost effectiveness • HEOR • Metastases • PK/PD data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

THE FIRE WITHIN: PARADOXICAL PULMONARY INFLAMMATION UNMASKED BY IMMUNE RECONSTITUTION (CHEST 2025) - "He was started on a fixed-dose combination therapy of cobicistat, darunavir, emtricitabine, and tenofovir alafenamide (Symtuza) alongside doxycycline for syphilis.Despite adherence to ART, the patient developed progressive fatigue, subjective fevers, dry cough, and worsening malaise, leading to hospital admission...Prednisone therapy was initiated, resulting in marked clinical improvement within 48 hours... Recognition, timely initiation of corticosteroid therapy, and coordinated multidisciplinary management crucial for improving outcomes in patients with IRIS. Early involving of infectious disease specialists and pulmonary consultation is essential to differentiate IRIS from progressive infections and to optimize management strategies. This case highlights the need for clinicians to remain vigilant for pulmonary IRIS in patients with advanced HIV starting ART, as early intervention can significantly improve prognosis."

Cough • Fatigue • Human Immunodeficiency Virus • Infectious Disease • Inflammation • Pneumonia • Tuberculosis • CD4

Drug-Drug Interaction (DDI) Liability of Bictegravir/Lenacapavir (BIC/LEN) Compared With Representative Complex Antiretroviral Therapy (ART) Regimens in the Phase 3 Portion of ARTISTRY-1 (EACS 2025) - P2/3 | "Purpose : People with HIV (PWH) who are on complex ART regimens often also take concomitant medications to treat comorbidities. A larger number of DDIs were identified for ART regimens containing boosted DRV compared with BIC/LEN, due to strong inhibition of drug-metabolism pathway components cytochrome P450 3A (CYP3A) and P-glycoprotein by pharmacokinetic enhancers cobicistat and ritonavir, in comparison with moderate CYP3A inhibition and weak P-glycoprotein inhibition by LEN. Conclusions : DDI liability of ART regimens varies, with advantages for BIC/LEN compared with pharmacokinetic enhancer–containing complex regimens."

Late-breaking abstract • P3 data • Human Immunodeficiency Virus • Infectious Disease

The Effects of Cobicistat and Voriconazole on the Safety, Pharmacokinetics, and Pharmacodynamics of the TLR7 Agonist Vesatolimod in People with HIV. (PubMed, Infect Dis Ther) - P1 | "VES was well tolerated when administered alone or in combination with COBI or VOR in PWH. Coadministration of COBI, but not VOR, increased plasma VES concentrations, suggesting that inhibition of transporters (P-gp and/or BCRP) may have a greater impact on VES PK than inhibition of the drug-metabolizing enzyme (CYP3A)."

IO biomarker • Journal • PK/PD data • Breast Cancer • Human Immunodeficiency Virus • Infectious Disease • Oncology • Solid Tumor

Clinical Activity and Safety of Novel BRAF Inhibitor (BRAFi) Plixorafenib (FORE8394; PLX8394) in Advanced Thyroid Cancers (TC) Harboring BRAF Alterations (ATA 2025) - P1/2 | "Safety and efficacy of plixorafenib for participants (pts) with BRAF-altered advanced thyroid cancer from a Phase 1/2a clinical trial are described.Methods This open-label, single-arm, multicenter, dose escalation/optimization study (NCT02428712) assessed safety, pharmacokinetics (PK), and preliminary efficacy of plixorafenib 900-3600 mg/day with or without cobicistat, a PK enhancer, in pts ≥10 years of age with BRAF-altered neoplasms, including thyroid cancers. One had confirmed PR lasting 17.8 months (treated for 27.7 months); 2 had SD (treated 44.4 and 3.7 months); and 1 had PD. One pt with ATC and a BRAF fusion had SD.Discussion/Conclusion Plixorafenib treatment had an encouraging safety profile and durable disease control in pts with BRAF-altered thyroid cancer that appears very favorable compared with historical data with standard treatment options."

Clinical • Metastases • Fatigue • Gastroenterology • Gastrointestinal Disorder • Oncology • Solid Tumor • Thyroid Gland Carcinoma • BRAF

Pharmacokinetic Properties of Antiretroviral and Anti-Tuberculosis Drugs During Pregnancy and Postpartum (clinicaltrials.gov) - P=N/A | N=205 | Completed | Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) | Active, not recruiting ➔ Completed

Trial completion • Human Immunodeficiency Virus • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

Efficacy and safety of emtricitabine/tenofovir alafenamide (F/TAF) plus cobicistat-boosted protease inhibitors in children with HIV-1 aged 2-<12 years and weighing 14-<40 kg: Week 48 outcomes (IAS-HIV 2025) - P2/3 | "BACKGROUND: TAF is a nucleoside reverse transcriptase inhibitor with improved renal and bone safety compared with tenofovir disoproxil fumarate. F/TAF is approved in Europe and the US for use with boosted protease inhibitors in adults and older children, and is being evaluated with cobicistat-boosted atazanavir (ATV/co) or darunavir (DRV/co) in younger children in an ongoing open-label Phase 2/3 trial (NCT02016924)... Over 48 weeks of treatment, F/TAF + ATV/co or DRV/co in children aged 2-<12 years and weighing 14-<40 kg maintained high rates of virologic suppression, with an acceptable safety profile. There were no renal, bone, or weight gain/loss concerns, supporting further evaluation of these drug combinations in pediatric populations."

Clinical • Hepatology • Human Immunodeficiency Virus • Infectious Disease • Pediatrics

Validation of a LC-MS/MS Assay for Rapid and Simultaneous Quantification of Cobicistat and Venetoclax in Human Plasma and Serum. (PubMed, Biomed Chromatogr) - "Clinical TDM samples showed mean concentrations ± standard deviation (SD) of 138.8 ± 123.3 μg/L for cobicistat and 1497.1 ± 1285.9 μg/L for venetoclax. The development and validation of this LC-MS/MS assay provide a reliable and efficient method for the simultaneous quantification of cobicistat and venetoclax in plasma and serum samples."

Journal

Osimertinib Cost Minimization in Non-Small Cell Lung Cancer (NSCLC) Treatment: Hypothesis Generation for a Population Pharmacokinetic Approach for Equivalent Dose Optimization of Osimertinib in Combination With Cobicistat. (PubMed, J Clin Pharmacol) - P1 | "However, this regimen was not equivalent for AZ5104 AUC0-144h (GMR [90% CI] = 0.67 [0.66-0.68]) and Cmax (GMR [90% CI] = 0.74 [0.73-0.76]). Theoretically, this reduced dose of cobicistat boosted osimertinib can potentially save approximately 33% in osimertinib treatment associated costs whilst maintaining adequate osimertinib exposure. Clinical Trials Registration: NCT03858491."

HEOR • Journal • PK/PD data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor

Pharmacokinetic Adaptations in Pregnancy: Implications for Optimizing Antiretroviral Therapy in HIV-Positive Women. (PubMed, Pharmaceutics) - "For example, drugs like lopinavir and atazanavir require dose adjustments, while dolutegravir maintains efficacy despite reduced plasma levels. Integrase inhibitors demonstrate favorable virological suppression, although cobicistat-boosted regimens show subtherapeutic levels...Incorporating TDM, leveraging pharmacogenomic insights, and prioritizing maternal and neonatal safety are critical for personalized ART management. Further research into long-acting formulations and global guideline harmonization is needed to address disparities in care and improve outcomes for HIV-positive pregnant women."

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

The Meandrous Route of Rilpivirine in the Search for the Miraculous Drug to Treat HIV Infections. (PubMed, Viruses) - "For this purpose, it was subsequently combined with tenofovir disoproxil fumarate (TDF), tenofovir alafenamide (TAF), darunavir (boosted with ritonavir or cobicistat) or dolutegravir. Its wide-spread use is thanks to its combination with cabotegravir (CAB) in the form of a long-acting intramuscular injection once per month (QM), later twice per month (Q2M), for the treatment of adults, later extended to adolescents and pregnant women, with HIV infections. The long-acting CAB plus RPV should not be administered in patients treated with rifampicin or rifabutin, patients with virological failure or patients with resistance to CAB or RPV, or patients with hepatitis B virus (HBV) infection. Long-acting CAB+RPV may lead to pain at the site of injection which would diminish over time."

Journal • Review • Hepatitis B • Human Immunodeficiency Virus • Infectious Disease • Inflammation • Pain

Mechanism of intermittent dosing of fluoxetine in premenstrual dysphoric disorder. (PubMed, Arch Womens Ment Health) - "Confirmation of this mechanism may open the door to non-SRI treatments for women that do not tolerate SRI agents."

Journal • CNS Disorders • Depression • Human Immunodeficiency Virus • Infectious Disease

Molecular Mechanism of Tenofovir Nephrotoxicity When Combined with an ABCC Inhibitor (ASM Microbe 2025) - "However, it is still unclear as to how PIs such as ritonavir (RTV) and Lopinavir (LPV) increase the risk for nephrotoxicity...Additional data will be further presented for other ANPs such as adefovir combined with escalating PIs or cobicistat on cytotoxicity... These findings suggest that overexpression of MRP4 and MRP5 could render resistance toward TFV-mediated toxicities, while MRP2 is most efficient in transporting TFV out of the cells. These findings affirmed that intracellular levels of ANPs such as TFV may be regulated by MRP2-mediated activity."

Human Immunodeficiency Virus • Infectious Disease • Nephrology • ABCB1 • ABCC2 • ABCC4

VENETOCLAX BOOSTING IN ACUTE MYELOID LEUKEMIA (AML): PRELIMINARY PHARMACOKINETIC RESULTS FROM THE HOVON 171 TRIAL (EHA 2025) - P2 | "The pivotal VIALE-A study established that addition of the BCL-2 inhibitor venetoclax to azacitidine (VEN/AZA) improved survival in unfit patients with AML. Reducing the venetoclax dose from 400 mg to 50 mg in combination with cobicistat results in at least equivalent venetoclax exposure compared to the unboosted dose. This boosted venetoclax exposure corresponds with the exposure obtained under label recommendations for dose reductions in combination with strong CYP3A4 inhibitors. The cobicistat facilitated venetoclax dose reduction allows for >85% savings on venetoclax-associated healthcare costs."

PK/PD data • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

Pediatric darunavir/cobicistat fixed-dose combination tablet for dispersion: Bioequivalence versus separate agents in healthy participants and acceptability in children living with human immunodeficiency virus-1. (PubMed, Antivir Ther) - "Acceptability questionnaires were completed by observers, participants and caregivers.ResultsThe bioequivalence study indicated that the geometric mean ratios for DRV maximum plasma concentration and area under the concentration-time curve of the dispersed DRV/COBI-600/90-mg FDC tablet versus the separate formulations fell within the 80-125% bioequivalence limits. In the acceptability study in children, per independent observers 83% (10/12) of the children were able to swallow the dispersion completely and rated the dispersed FDC tablet as "ok" to "very easy" to swallow.ConclusionThe DRV/COBI 600/90-mg FDC tablet dispersed in water was bioequivalent to coadministration of the separate formulations and was acceptable for long-term daily use in the intended pediatric population."

Clinical • Journal • Human Immunodeficiency Virus • Infectious Disease • Pediatrics

Pharmacokinetic Properties of Antiretroviral and Anti-Tuberculosis Drugs During Pregnancy and Postpartum (clinicaltrials.gov) - P=N/A | N=205 | Active, not recruiting | Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) | Trial primary completion date: Apr 2025 ➔ Jul 2025 | Completed ➔ Active, not recruiting | Trial completion date: Apr 2025 ➔ Jul 2025

Enrollment closed • Trial completion date • Trial primary completion date • Human Immunodeficiency Virus • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

Maintenance therapy with dolutegravir and lamivudine versus bictegravir, emtricitabine, and tenofovir alafenamide in people with HIV (PASO-DOBLE): 48-week results from a randomised, multicentre, open-label, non-inferiority trial. (PubMed, Lancet HIV) - "These results provide further evidence that might be useful in shared decision-making between physicians and people living with HIV regarding switching oral antiretroviral therapy."

Head-to-Head • Journal • Human Immunodeficiency Virus • Infectious Disease • Musculoskeletal Diseases • Psychiatry