ViiV HEALTHCARE TO SHOWCASE INNOVATIVE HIV TREATMENT AND PREVENTION PORTFOLIO AT IDWEEKTM AND HIV GLASGOW
More than 50 abstracts at the two scientific congresses will showcase new mechanisms of action, implementation of the only complete long-acting treatment regimen and key insights into real-world treatment outcomes
London, 12 October 2022 – ViiV Healthcare, the global specialist HIV company majority-owned by GSK, with Pfizer and Shionogi as shareholders, today announced the presentation of over 50 abstracts from the company’s diverse portfolio of innovative licensed treatment and prevention options at IDWeek™ 2022, being held in Washington, D.C., from 19 – 23 October and at HIV Glasgow taking place between 23 – 26 October 2022 in Glasgow, Scotland.
Kimberly Smith, M.D., MPH, Head of Research & Development at ViiV Healthcare, said: “As the only pharmaceutical company solely focused on HIV, we’re excited to share our pioneering research findings at IDWeek™ and HIV Glasgow that are focused on helping to address the evolving needs of those impacted by HIV. Presentations will showcase our continued innovation across both HIV treatment and prevention, and include first-time findings from our early pipeline as well as implementation data and real-world evidence from our established treatment portfolio. We look forward to joining scientific leaders from around the world to advance the collective understanding of HIV and promote new solutions to care together.”
Advancing innovation in HIV research
At HIV Glasgow, ViiV Healthcare will be sharing findings from the BANNER study, a phase IIa proof-of-concept study of N6LS (VH3810109), a novel, investigational, broadly neutralising antibody (bNAb) that is being investigated in adults living with HIV at two dosing levels – a high dose and ten-fold lower dose (40 mg/kg and ~4 mg/kg (280 mg)), respectively. N6LS works by binding to a specific site (gp120) on the surface of HIV that prevents its entry into immune system cells (CD4+ T-cells). By blocking HIV’s entry into human CD4+ cells, the virus is unable to replicate, and the HIV transmission process may be prevented. Researchers will share the proof-of-concept findings evaluating the safety, pharmacokinetics, and antiviral activity of a single IV infusion of N6LS in treatment-naïve people living with HIV.1
Data from the HPTN 083 study will also be presented at HIV Glasgow, providing further analysis of the efficacy of Apretude (cabotegravir long-acting) for pre-exposure prophylaxis (PrEP) in men who have sex with men and transgender women in the first year after unblinding the study.2
Implementing long-acting treatment in a clinical setting
ViiV Healthcare will share results from its pioneering implementation science program that aims to identify successful methods of integrating its medicines for HIV treatment in the clinical setting. The CARISEL study evaluates the best approaches to implementing Vocabria/Rekambys (cabotegravir, rilpivirine; marketed as Cabenuva in the US) administered every two months into clinical practice in Europe. Clinical results will be presented at IDWeek™ followed by primary results of the study at HIV Glasgow. Data to be presented include efficacy and safety results, implementation outcomes and people living with HIV, healthcare professionals and staff preferences in a number of European clinics, through different implementation strategies across a diverse (gender, race and age) population living with HIV.3
Additionally, patient-reported outcomes from the phase IIIb ATLAS-2M study of virologically suppressed adults living with HIV-1 following 152 weeks of HIV maintenance therapy with CAB + RPV LA will be presented at HIV Glasgow. Participants shared details of treatment satisfaction, preferences, and acceptability of injections.4
Establishing real-world evidence for 2-drug and long-acting regimens
Real-world evidence, which is data derived from studies fielded in a real-world setting, can provide a fuller understanding of a therapy, how it works in clinical practice, and how to address the evolving needs of people living with HIV. ViiV Healthcare will present findings from real-world studies of its HIV therapies as an essential tool to help bridge the gap between clinical trials and clinical practice.
Data from the OPERA cohort to be presented at IDWeek™ compare real-world safety and effectiveness data in virologically suppressed adults taking Dovato (dolutegravir, lamivudine) with those taking a bictegravir- or dolutegravir-based 3-drug regimen.5
ViiV Healthcare will also be presenting six-month implementation results from the CARLOS study at HIV Glasgow investigating effectiveness, adherence and patient reported outcomes alongside provider perceptions following the integration of CAB + RPV LA in German clinics.6,7 Additional data from the BEYOND study of CAB + RPV LA provide further insights into US physician perceptions on administration and implementation of the long-acting therapy in their practice will be presented at IDWeek™.8
Here is a list of ViiV Healthcare and partner study data to be presented at IDWeek™ and HIV Glasgow:
Data to be presented at IDWeek™
| Abstract title | First Author | Presentation |
| Dolutegravir | ||
| Systematic Literature Review of Real-world Experience with the 2-Drug Regimen Dolutegravir and Lamivudine in People with HIV Who Would Not Have Met Inclusion Criteria for the Phase 3 Clinical Program | J. Slim |
Poster |
| Efficacy and Safety of Switching to DTG/3TC in Virologically Suppressed PLWH by Age, Including Those Aged ≥65 Years: Pooled Results from the TANGO and SALSA Studies | M. Prakash | Poster |
| Suppressed Switch to DTG/3TC 2-Drug Regimen vs BIC- or DTG-Based 3-Drug Regimens | G. Pierone | Rapid-Fire Poster* |
| Effectiveness and Durability of Dolutegravir (DTG) Based Regimens in Older People Living with HIV (PLWH) from the Veterans Aging Cohort Study (VACS) | L. Yan | Poster |
| Real World Treatment Experience of Treatment-Naive People with HIV Who Initiated Treatment with Single Tablet Dolutegravir/Lamivudine in a Test and Treat Setting in the US | J. Kuretski | Poster |
| Real World Treatment Experience of Single Tablet Dolutegravir/Lamivudine in Those Naive to Treatment with Baseline Viral Loads ≥100,000 Copies/mL in the US | P. Benson | Poster |
| A Real-world Observational Study on HIV-Infected Patients Who Switched from Nevirapine + 2 Nucleoside Reverse Transcriptase Inhibitors to Dolutegravir/Lamivudine in British Columbia, Canada | J. de Wet | Poster |
| Cabotegravir for Treatment | ||
| CARISEL: A Hybrid III Implementation Effectiveness Study of Implementation of Cabotegravir Plus Rilpivirine Long Acting (CAB+RPV LA) in EU Health Care Settings; Key Clinical and Implementation Outcomes by Implementation Arm | S. de Wit | Oral |
| Phase 3/3b Experience with Long-Acting Cabotegravir and Rilpivirine: Efficacy and Safety Outcomes Through Week 96 by Race | P. Patel | Oral |
| Real-world Use of Long-Acting Cabotegravir + Rilpivirine in the US: Effectiveness in the First Year | M. G. Sension | Oral |
| US Healthcare Provider Perspectives on the Initiation of Cabotegravir and Rilpivirine Long-Acting (CAB+RPV LA) in an Observational Real-world Study (BEYOND) | R. Hsu | Poster |
| Cabotegravir for PrEP | ||
| Awareness and Interest in PrEP Options Among US Cisgender Women – A National Survey | T. Poteat | Oral |
| PrEP Interest and Preferences Among US Black and Hispanic Men – A National Survey | T. Poteat | Poster |
| Relative Patient Preferences for Starting Daily, On-Demand, and Long-Acting Injectable HIV Pre-exposure Prophylaxis Among US Men Who Have Sex with Men, 2021-2022 | T. Sanchez | Rapid-Fire Poster* |
| Fostemsavir | ||
| Durability and Effectiveness of Fostemsavir in Heavily Treatment-Experienced People with HIV | R. K. Hsu | Rapid-Fire Poster* |
| General | ||
| An Increase in Single-Tablet Regimen (STR) Utilisation for People Living with HIV (PLWH) Enrolled in Medicaid Had Minimal Impact on Pharmacy Costs | A. P. Brogan | Poster |
| Clinical and Sociodemographic Characteristics Associated with Poor Self-rated Health Across Multiple Domains Among Older North American Adults Living with HIV | M. Dominguez | Poster |
| Single-Tablet Regimens (STR) Offer Better Persistence and Adherence, with Lower Costs by Adherence Status, Than Multiple-Tablet Regimens (MTR) for People Living with HIV (PLWH) Enrolled in Medicaid | A. P. Brogan | Poster |
*Rapid-Fire Poster indicates mini oral session
Data to be presented at HIV Glasgow
| Abstract Title | First Author | Presentation |
| Dolutegravir | ||
| Durable Efficacy of Switching from a 3-/4-Drug Tenofovir Alafenamide (TAF)-Based Regimen to the 2-Drug Regimen Dolutegravir/Lamivudine (DTG/3TC) in the TANGO Study Through Week 196 | S. De Wit |
Mini-oral |
| Risk of Tuberculosis After Initiation of Antiretroviral Therapy Among People Living with HIV in Europe | I. S. Johansen |
Oral |
| Efficacy and Safety of Dolutegravir/Lamivudine (DTG/3TC) in Black and Asian Participants from TANGO and SALSA: Pooled 48-Week Data Analyzed by Race | P. Kumar | Poster |
| Patient-Reported Symptom Outcomes Following DTG/3TC Use in a Test and Treat Setting: Results from the STAT Study | A. Oglesby | Poster |
| High Efficacy of Dolutegravir/Lamivudine (DTG/3TC) in Treatment-Naive Adults with HIV-1 and High Baseline Viral Load (VL): 48-Week Subgroup Analyses of the GEMINI-1/-2 and STAT Trials | C. Rolle | Poster |
| Efficacy and Safety of Switching to Dolutegravir Plus Rilpivirine in Virologically Suppressed Older PLWH: Pooled Week 148 Results from SWORD-1 and SWORD-2 | M. Prakash | Poster |
| Systematic Literature Review of Real-World Experience with the 2-Drug Regimen Dolutegravir and Lamivudine in People with HIV Who Would Not Have Met Inclusion Criteria for the Phase 3 Clinical Program (Encore) | J. Slim | Poster |
| Real-World Experience with the 2-Drug Regimen Dolutegravir and Lamivudine in Women with HIV: A Systematic Literature Review | S. di Giambenedetto | Poster |
| Lipid Changes in Real-World Studies with the 2-Drug Regimen Dolutegravir and Lamivudine (DTG + 3TC) in People with HIV-1: A Systematic Literature Review | E. Letang | Poster |
| Effectiveness of Dolutegravir + Lamivudine in Real-World Studies in People with HIV-1 with M184V/I Mutations: A Systematic Review and Meta-Analysis | M. Kabra | Poster |
| Treatment-Emergent Integrase Inhibitor Resistance Among Pediatric and Adolescent HIV-1 Populations: A Systematic Review | C. Henegar | Poster |
| Initial Plasma HIV-1 RNA and CD4+ T-Cell Count Are Determinants of Virological Outcomes with Initial Integrase Inhibitor-Based Regimens: A Prospective Multinational RESPOND Cohort Consortium | H. Álvarez | Poster |
| 2 Year Outcomes of Dolutegravir (DTG) + Lamivudine (3TC) in ART-Naive and Pre-Treated People Living with HIV in Germany: Real-World Data from the German URBAN Cohort | D. Beer | Poster |
| 3-Year Outcomes of Dolutegravir/Rilpivirine in Virologically Suppressed PLHIV: Real-World Data from the Prospective German JUNGLE Cohort | F. Schabaz | Poster |
| Use of Preventive Measures for Cardiovascular Disease in People Living with HIV | N. Jaschinski | Poster |
| Real World Use of Dolutegravir/Lamivudine in Treatment Naive People Living with HIV During the COVID Pandemic | G. Pierone | Poster |
| Real-World Data from the Prospective, Multicenter Study on the Use of Dolutegravir-Based Regimens (DBRs) in ART-Naive and Experienced People Living with HIV: 12-Months Results from the Russian TESLA Study | S. Kuznetsov | Poster |
| Cabotegravir for Treatment | ||
| Expanded Multivariable Models to Assist Patient Selection for Long-Acting Cabotegravir+Rilpivirine Treatment: Clinical Utility of a Combination of Patient, Drug Concentration, and Viral Factors Associated with Virologic Failure Over 152 Weeks | C. Orkin | Oral |
| 6-Month Outcomes of Every 2-Months Long-Acting Cabotegravir and Rilpivirine in a Real-World Setting – Effectiveness, Adherence to Injections and Patient Reported Outcomes from PLHIV in the German CARLOS Cohort | J. Borch | Oral |
| HIV-1 RNA Blips, Low-Level Viral Replication and Mean CD4+/CD8+ Ratio During Phase 3 Cabotegravir + Rilpivirine Long-Acting Study (FLAIR) are Similar to Oral 3-Drug Therapy Through Week 96 | C. Latham | Poster |
| Patient-Reported Outcomes After 152 Weeks of HIV Maintenance Therapy with Long-Acting Cabotegravir + Rilpivirine in the Phase 3b ATLAS-2M Study | V. Chounta | Poster |
| Drug-Related Neuropsychiatric Adverse Events Across Phase 3/3b Studies of Long-Acting Cabotegravir + Rilpivirine Through Week 48 | E. Elliot | Poster |
| The Implementation of Every 2-Months Cabotegravir and Rilpivirine Long-Acting Injections from the Perspective of Healthcare Providers in the German CARLOS Cohort, 6-Month Outcomes | J. Scherzer | Poster |
| Perceptions of Cabotegravir and Rilpivirine Long-Acting (CAB+RPV LA) from Patients in the CAB+RPV Implementation Study in European Locations (CARISEL) | T. Lutz | Poster |
| Overcoming Barriers and Achieving Optimal Implementation of Cabotegravir and Rilpivirine Long-Acting (CAB+RPV LA): Staff Study Participant (SSP) Results from the CAB+RPV Implementation Study in European Locations (CARISEL) | L. Slama | Poster |
| Implementation of Cabotegravir and Rilpivirine Long-Acting (CAB+RPV LA): Primary Results from the CAB+RPV Implementation Study in European Locations (CARISEL) | B. J. van Welzen | Poster |
| Cabotegravir for PrEP Collaborative Study | ||
| Laboratory analysis of HIV infections in the Year 1 unblinded period of HPTN 083: injectable cabotegravir for PrEP in MSM and TGW | M. A. Marzinke | Oral |
| Fostemsavir | ||
| Efficacy and Safety of Fostemsavir Plus Optimised Background Therapy in Heavily Treatment-Experienced Adults with HIV-1: Week 240 Results of the Phase 3 BRIGHTE Study (encore) | J. Aberg | Poster |
| A Multivariable Analysis of the Phase 3 BRIGHTE Trial, Through Week 24, to Identify Predictors of Virologic Response to Fostemsavir in Heavily Treatment-Experienced People Living with HIV | M. Gartland | Poster |
| Fostemsavir and QT Prolongation: Clinical Applications for Co-Administration with Other Agents | S. Patel | Poster |
| Maturation Inhibitor GSK 3640254 | ||
| Effects of the HIV-1 Maturation Inhibitor GSK3640254 on QT Interval in Healthy Participants | Y. Zhang | Poster |
| Pipeline | ||
| VH3810109 (N6LS) Reduces Viremia Across a Range of Doses in ART-Naive Adults Living with HIV: Proof of Concept Achieved in the Phase IIa BANNER (207959, NCT04871113) Study | P. Leone | Oral |
| General | ||
| Age Related Differences in Quality of Life Outcomes of People Living with HIV | A. Clark | Poster |
APRETUDE (cabotegravir) extended-release injectable suspensions
INDICATION
APRETUDE is indicated in at-risk adults and adolescents weighing at least 35 kg for pre-exposure prophylaxis (PrEP) to reduce the risk of sexually acquired HIV-1 infection. Individuals must have a negative HIV-1 test prior to initiating APRETUDE (with or without an oral lead-in with oral cabotegravir) for HIV-1 PrEP.
IMPORTANT SAFETY INFORMATION
BOXED WARNING: RISK OF DRUG RESISTANCE WITH USE OF APRETUDE FOR HIV-1 PRE-EXPOSURE PROPHYLAXIS (PrEP) IN UNDIAGNOSED EARLY HIV-1 INFECTION
Individuals must be tested for HIV-1 infection prior to initiating APRETUDE or oral cabotegravir, and with each subsequent injection of APRETUDE, using a test approved or cleared by the FDA for the diagnosis of acute or primary HIV-1 infection. Drug-resistant HIV-1 variants have been identified with use of APRETUDE by individuals with undiagnosed HIV-1 infection. Do not initiate APRETUDE for HIV-1 PrEP unless negative infection status is confirmed. Individuals who become infected with HIV-1 while receiving APRETUDE for PrEP must transition to a complete HIV-1 treatment regimen.
CONTRAINDICATIONS
- Do not use APRETUDE in individuals:
- with unknown or positive HIV-1 status
- with previous hypersensitivity reaction to cabotegravir
- receiving carbamazepine, oxcarbazepine, phenobarbital, phenytoin, rifampin, and rifapentine
WARNINGS AND PRECAUTIONS
Comprehensive Management to Reduce the Risk of HIV-1 Infection:
- Use APRETUDE as part of a comprehensive prevention strategy, including adherence to the administration schedule and safer sex practices, including condoms, to reduce the risk of sexually transmitted infections (STIs). APRETUDE is not always effective in preventing HIV-1 acquisition. Risk for HIV-1 acquisition includes, but is not limited to, condomless sex, past or current STIs, self-identified HIV risk, having sexual partners of unknown HIV-1 viremic status, or sexual activity in a high prevalence area or network. Inform, counsel, and support individuals on the use of other prevention measures (e.g., consistent and correct condom use; knowledge of partner[s] HIV-1 status, including viral suppression status; regular testing for STIs)
- Use APRETUDE only in individuals confirmed to be HIV-1 negative. HIV-1 resistance substitutions may emerge in individuals with undiagnosed HIV-1 infection who are taking only APRETUDE, because APRETUDE alone does not constitute a complete regimen for HIV-1 treatment. Prior to initiating APRETUDE, ask seronegative individuals about recent (in past month) potential exposure events and evaluate for current or recent signs or symptoms consistent with acute HIV-1 infection (e.g., fever, fatigue, myalgia, skin rash). If recent (<1 month) exposures to HIV-1 are suspected or clinical symptoms consistent with acute HIV-1 infection are present, use a test approved or cleared by the FDA as an aid in the diagnosis of acute HIV-1 infection
- When using APRETUDE, HIV-1 testing should be repeated prior to each injection and upon diagnosis of any other STIs
- Additional HIV testing to determine HIV status is needed if an HIV-1 test indicates possible HIV-1 infection or if symptoms consistent with acute HIV-1 infection develop following an exposure event. If HIV-1 infection is confirmed, then transition the individual to a complete HIV-1 treatment
- Counsel HIV-1 uninfected individuals to strictly adhere to the recommended dosing and testing schedule for APRETUDE
Potential Risk of Resistance with APRETUDE:
- There is a potential risk of developing resistance to APRETUDE if an individual acquires HIV-1 either before, while taking, or following discontinuation of APRETUDE. To minimize this risk, it is essential to clinically reassess individuals for risk of HIV-1 acquisition and to test before each injection to confirm HIV-1–negative status. Individuals who are confirmed to have HIV-1 infection must transition to a complete HIV-1 treatment. If individuals at continuing risk of HIV-1 acquisition discontinue APRETUDE, alternative forms of PrEP should be considered and initiated within 2 months of the final injection of APRETUDE
Long-Acting Properties and Potential Associated Risks with APRETUDE:
- Residual concentrations of cabotegravir may remain in the systemic circulation of individuals for prolonged periods (up to 12 months or longer). Take the prolonged-release characteristics of cabotegravir into consideration and carefully select individuals who agree to the required every-2-month injection dosing schedule because non-adherence or missed doses could lead to HIV-1 acquisition and development of resistance
Hypersensitivity Reactions:
- Serious or severe hypersensitivity reactions have been reported in association with other integrase inhibitors and could occur with APRETUDE
- Discontinue APRETUDE immediately if signs or symptoms of hypersensitivity reactions develop. Clinical status, including liver transaminases, should be monitored and appropriate therapy initiated
Hepatotoxicity:
- Hepatotoxicity has been reported in a limited number of individuals receiving cabotegravir with or without known pre-existing hepatic disease or identifiable risk factors
- Clinical and laboratory monitoring should be considered and APRETUDE should be discontinued if hepatotoxicity is suspected and individuals managed as clinically indicated
Depressive Disorders:
- Depressive disorders (including depression, depressed mood, major depression, persistent depressive disorder, suicidal ideation or attempt) have been reported with APRETUDE
- Promptly evaluate patients with depressive symptoms
Risk of Reduced Drug Concentration of APRETUDE Due to Drug Interactions:
- The concomitant use of APRETUDE and other drugs may result in reduced drug concentration of APRETUDE
- Refer to the full Prescribing Information for steps to prevent or manage these possible and known significant drug interactions, including dosing recommendations. Consider the potential for drug interactions prior to and during use of, and after discontinuation of APRETUDE; review concomitant medications during use of APRETUDE
ADVERSE REACTIONS
The most common adverse reactions (incidence ≥1%, all grades) with APRETUDE were injection site reactions, diarrhoea, headache, pyrexia, fatigue, sleep disorders, nausea, dizziness, flatulence, abdominal pain, vomiting, myalgia, rash, decreased appetite, somnolence, back pain, and upper respiratory tract infection.
DRUG INTERACTIONS
- Refer to the full Prescribing Information for important drug interactions with APRETUDE
- Drugs that induce UGT1A1 may significantly decrease the plasma concentrations of cabotegravir
USE IN SPECIFIC POPULATIONS
- Lactation: Assess the benefit-risk of using APRETUDE to the infant while breastfeeding due to the potential for adverse reactions and residual concentrations in the systemic circulation for up to 12 months or longer after discontinuation
- Pediatrics: Not recommended in individuals weighing less than 35 kg
Please see full Prescribing Information for APRETUDE.
Important Safety Information for Dovato (50mg dolutegravir/300mg lamivudine) Tablets
INDICATION
Dovato is indicated as a complete regimen to treat HIV-1 infection in adults with no antiretroviral (ARV) treatment history or to replace the current ARV regimen in those who are virologically suppressed (HIV-1 RNA <50 copies/mL) on a stable ARV regimen with no history of treatment failure and no known resistance to any component of Dovato.
IMPORTANT SAFETY INFORMATION
BOXED WARNING: PATIENTS CO-INFECTED WITH HEPATITIS B VIRUS (HBV) AND HIV-1: EMERGENCE OF LAMIVUDINE-RESISTANT HBV AND EXACERBATIONS OF HBV
All patients with HIV-1 should be tested for the presence of HBV prior to or when initiating Dovato. Emergence of lamivudine-resistant HBV variants associated with lamivudine-containing antiretroviral regimens has been reported. If Dovato is used in patients co-infected with HIV-1 and HBV, additional treatment should be considered for appropriate treatment of chronic HBV; otherwise, consider an alternative regimen.
Severe acute exacerbations of HBV have been reported in patients who are co-infected with HIV-1 and HBV and have discontinued lamivudine, a component of Dovato. Closely monitor hepatic function in these patients and, if appropriate, initiate anti-HBV treatment.
Contraindications
- Do not use Dovato in patients with previous hypersensitivity reaction to dolutegravir or lamivudine
- Do not use Dovato in patients receiving dofetilide
Warnings and precautions
Hypersensitivity Reactions:
- Hypersensitivity reactions have been reported with dolutegravir and were characterized by rash, constitutional findings, and sometimes organ dysfunction, including liver injury
- Discontinue Dovato immediately if signs or symptoms of severe skin or hypersensitivity reactions develop, as a delay in stopping treatment may result in a life-threatening reaction. Clinical status, including liver aminotransferases, should be monitored and appropriate therapy initiated
Hepatotoxicity:
- Hepatic adverse events have been reported, including cases of hepatic toxicity (elevated serum liver biochemistries, hepatitis, and acute liver failure), in patients receiving a dolutegravir-containing regimen without pre-existing hepatic disease or other identifiable risk factors
- Patients with underlying hepatitis B or C or marked elevations in transaminases prior to treatment may be at increased risk for worsening or development of transaminase elevations with use of Dovato. In some cases, the elevations in transaminases were consistent with immune reconstitution syndrome or hepatitis B reactivation, particularly in the setting where anti-hepatitis therapy was withdrawn
- Monitoring for hepatotoxicity is recommended
Embryo Fetal Toxicity:
- Assess the risks and benefits of Dovato and discuss with the patient to determine if an alternative treatment should be considered at the time of conception through the first trimester of pregnancy due to the risk of neural tube defects
- Pregnancy testing is recommended before initiation of Dovato. Individuals of childbearing potential should be counselled on the consistent use of effective contraception
Lactic Acidosis and Severe Hepatomegaly with Steatosis:
Fatal cases have been reported with the use of nucleoside analogues, including lamivudine. Discontinue Dovato if clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity develop, including hepatomegaly and steatosis in the absence of marked transaminase elevations.
Adverse Reactions or Loss of Virologic Response Due to Drug Interactions with concomitant use of Dovato and other drugs may occur (see Contraindications and Drug interactions).
Immune Reconstitution Syndrome, including the occurrence of autoimmune disorders with variable time to onset, has been reported with the use of Dovato.
Adverse reactions
The most common adverse reactions (incidence ≥2%, all grades) with Dovato were headache (3%), nausea (2%), diarrhoea (2%), insomnia (2%), fatigue (2%), and anxiety (2%).
Drug interactions
- Consult full Prescribing Information for Dovato for more information on potentially significant drug interactions
- Dovato is a complete regimen. Coadministration with other antiretroviral medications for the treatment of HIV-1 infection is not recommended
- Drugs that induce or inhibit CYP3A or UGT1A1 may affect the plasma concentrations of dolutegravir
- Administer Dovato 2 hours before or 6 hours after taking polyvalent cation-containing antacids or laxatives, sucralfate, oral supplements containing iron or calcium, or buffered medications. Alternatively, Dovato and supplements containing calcium or iron can be taken with food
Use in specific populations
- Pregnancy: The safety and efficacy of a dual regimen has not been studied in pregnancy. If a pregnancy is confirmed in the first trimester while on Dovato, the benefits and risks of continuing Dovato versus switching to another antiretroviral regimen should be discussed with the patient taking the gestational age and the critical time period of neural tube defect development into account. Data analysed from the Antiretroviral Pregnancy Registry do not indicate an increased risk of major birth defects in women exposed to dolutegravir during pregnancy but are currently insufficient to address the risk of neural tube defects. Dovato may be used during the second and third trimester of pregnancy when the expected benefit justifies the potential risk to the foetus.
- Lactation: Breastfeeding is not recommended due to the potential for HIV-1 transmission.
- Women of childbearing potential (WOCBP): WOCBP should be counselled about the potential risk of neural tube defects with dolutegravir (a component of Dovato), including consideration of effective contraceptive measures. If a woman plans pregnancy, the benefits and the risks of continuing treatment with Dovato should be discussed with the patient. Renal Impairment: Dovato is not recommended for patients with creatinine clearance <30 mL/min. Patients with a sustained creatinine clearance between 30 and 49 mL/min should be monitored for hematologic toxicities, which may require a dosage adjustment of lamivudine as an individual component
- Hepatic Impairment: Dovato is not recommended in patients with severe hepatic impairment (Child-Pugh Score C)
Please refer to the full European Summary of Product Characteristics for Dovato for full prescribing information, including contraindications, special warnings and precautions for use. For the US, please refer to the US Prescribing Information, including Boxed Warning.
Important Safety Information for Cabenuva (cabotegravir 200mg/mL; rilpivirine 300mg/mL) extended-release injectable suspensions (marketed as Vocabria/Rekambys outside the US)
Cabenuva is indicated as a complete regimen for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in adults and adolescents who are 12 years of age or older and weighing at least 35 kg to replace the current antiretroviral regimen in those who are virologically suppressed (HIV-1 RNA less than <50 copies per /mL) on a stable antiretroviral regimen with no history of treatment failure and with no known or suspected resistance to either cabotegravir or rilpivirine.
CONTRAINDICATIONS
- Do not use Cabenuva in patients with previous hypersensitivity reaction to cabotegravir or rilpivirine
- Do not use Cabenuva in patients receiving carbamazepine, oxcarbazepine, phenobarbital, phenytoin, rifabutin, rifampin, rifapentine, systemic dexamethasone (>1 dose), and St John’s wort
WARNINGS AND PRECAUTIONS
Hypersensitivity Reactions:
- Hypersensitivity reactions, including cases of Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), have been reported during postmarketing experience with rilpivirine-containing regimens. While some skin reactions were accompanied by constitutional symptoms such as fever, other skin reactions were associated with organ dysfunctions, including elevations in hepatic serum biochemistries
- Serious or severe hypersensitivity reactions have been reported in association with other integrase inhibitors and could occur with Cabenuva
- Discontinue Cabenuva immediately if signs or symptoms of hypersensitivity reactions develop. Clinical status, including liver transaminases, should be monitored and appropriate therapy initiated.
Post-Injection Reactions:
- Serious post-injection reactions (reported in less than 1% of subjects) were reported within minutes after the injection of rilpivirine, including dyspnea, bronchospasm, agitation, abdominal cramping, rash/urticaria, dizziness, flushing, sweating, oral numbness, changes in blood pressure, and pain (e.g., back and chest). These events may have been associated with inadvertent (partial) intravenous administration and began to resolve within a few minutes after the injection
- Carefully follow the Instructions for Use when preparing and administering Cabenuva. The suspensions should be injected slowly via intramuscular injection and avoid accidental intravenous administration. Observe patients briefly (approximately 10 minutes) after the injection. If a post-injection reaction occurs, monitor and treat as clinically indicated
Hepatotoxicity:
- Hepatotoxicity has been reported in patients receiving cabotegravir or rilpivirine with or without known pre-existing hepatic disease or identifiable risk factors
- Patients with underlying liver disease or marked elevations in transaminases prior to treatment may be at increased risk for worsening or development of transaminase elevations
- Monitoring of liver chemistries is recommended and treatment with Cabenuva should be discontinued if hepatotoxicity is suspected
Depressive Disorders:
- Depressive disorders (including depressed mood, depression, major depression, mood altered, mood swings, dysphoria, negative thoughts, suicidal ideation or attempt) have been reported with Cabenuva or the individual products
- Promptly evaluate patients with depressive symptoms
Risk of Adverse Reactions or Loss of Virologic Response Due to Drug Interactions:
- The concomitant use of Cabenuva and other drugs may result in known or potentially significant drug interactions (see Contraindications and Drug Interactions)
- Rilpivirine doses 3 and 12 times higher than the recommended oral dosage can prolong the QTc interval
- Cabenuva should be used with caution in combination with drugs with a known risk of Torsade de Pointes
Long-Acting Properties and Potential Associated Risks with Cabenuva:
- Residual concentrations of cabotegravir and rilpivirine may remain in the systemic circulation of patients for prolonged periods (up to 12 months or longer). Select appropriate patients who agree to the required monthly or every-2-month injection dosing schedule because non-adherence could lead to loss of virologic response and development of resistance
- To minimize the potential risk of developing viral resistance, it is essential to initiate an alternative, fully suppressive antiretroviral regimen no later than 1 month after the final injection doses of Cabenuva when dosed monthly and no later than 2 months after the final injections of Cabenuva when dosed every 2 months. If virologic failure is suspected, switch the patient to an alternative regimen as soon as possible
ADVERSE REACTIONS
- The most common adverse reactions (incidence ≥2%, all grades) with Cabenuva were injection site reactions, pyrexia, fatigue, headache, musculoskeletal pain, nausea, sleep disorders, dizziness, and rash
- The safety of Cabenuva in adolescents is expected to be similar to adults
DRUG INTERACTIONS
- Refer to the applicable full Prescribing Information for important drug interactions with Cabenuva, VOCABRIA, or EDURANT
- Because Cabenuva is a complete regimen, coadministration with other antiretroviral medications for the treatment of HIV-1 infection is not recommended
- Drugs that are strong inducers of UGT1A1 or 1A9 are expected to decrease the plasma concentrations of cabotegravir. Drugs that induce or inhibit CYP3A may affect the plasma concentrations of rilpivirine
- Cabenuva should be used with caution in combination with drugs with a known risk of Torsade de Pointes
USE IN SPECIFIC POPULATIONS
- Pregnancy: There are insufficient human data on the use of Cabenuva during pregnancy to adequately assess a drug-associated risk for birth defects and miscarriage. Discuss the benefit-risk of using Cabenuva during pregnancy and conception and consider that cabotegravir and rilpivirine are detected in systemic circulation for up to 12 months or longer after discontinuing injections of Cabenuva. An Antiretroviral Pregnancy Registry has been established
- Lactation: The CDC recommends that HIV 1−infected mothers in the United States not breastfeed their infants to avoid risking postnatal transmission of HIV-1 infection. Breastfeeding is also not recommended due to the potential for developing viral resistance in HIV-positive infants, adverse reactions in a breastfed infant, and detectable cabotegravir and rilpivirine concentrations in systemic circulation for up to 12 months or longer after discontinuing injections of Cabenuva
For more information please see US Prescribing Information for Cabenuva.
Important Safety Information for Rukobia (fostemsavir), 600 mg extended-release tablets
INDICATIONS AND USAGE
- RUKOBIA, a human immunodeficiency virus type 1 (HIV-1) gp120-directed attachment inhibitor, in combination with other antiretroviral(s), is indicated for the treatment of HIV-1 infection in heavily treatment-experienced adults with multidrug-resistant HIV-1 infection failing their current antiretroviral regimen due to resistance, intolerance, or safety considerations.
CONTRAINDICATIONS
- Do not use in patients with previous hypersensitivity to fostemsavir or any of the components of RUKOBIA.
- Do not use RUKOBIA in patients receiving strong cytochrome P450 (CYP)3A inducers, including but not limited to enzalutamide, carbamazepine, phenytoin, rifampin, mitotane, and St John’s wort (Hypericum perforatum).
WARNINGS AND PRECAUTIONS
- Immune Reconstitution Syndrome, including the occurrence of autoimmune disorders with variable time to onset, has been reported with the use of RUKOBIA.
- QTc Prolongation with Higher than Recommended Dosages: RUKOBIA at 2,400 mg twice daily has been shown to significantly prolong the QTc interval of the electrocardiogram. Use RUKOBIA with caution in patients with a history of QTc interval prolongation or in patients with relevant pre-existing cardiac disease or who are taking drugs with a known risk of Torsade de Pointes. Elderly patients may be more susceptible to drug-induced QT interval prolongation.
Elevations in Hepatic Transaminases in Patients with Hepatitis B or C Virus Co-infection:
- Monitoring of liver chemistries is recommended in patients with hepatitis B and/or C co-infection.
- Diligence should be applied in initiating or maintaining effective hepatitis B therapy when starting RUKOBIA in patients co-infected with hepatitis B.
Adverse Reactions or Loss of Virologic Response Due to Drug Interactions with concomitant use of RUKOBIA and other drugs may occur (see Contraindications and Drug Interactions).
ADVERSE REACTIONS
- The most common adverse reaction (all grades, randomized cohort) observed in ≥5% of subjects was nausea (10%).
- 81% of adverse reactions reported with RUKOBIA were mild or moderate in severity.
DRUG INTERACTIONS
- See the full Prescribing Information for RUKOBIA for a complete list of significant drug interactions.
- Temsavir may increase plasma concentrations of grazoprevir and voxilaprevir. Use an alternative hepatitis C virus regimen if possible.
- Use the lowest possible starting dose for statins and monitor for statin-associated adverse events.
- Patients receiving RUKOBIA should not take doses of estrogen-based therapies, including oral contraceptives, that contain more than 30 mcg/day of ethinyl estradiol. Caution is advised particularly in patients with additional risk factors for thromboembolic events.
USE IN SPECIFIC POPULATIONS
- Pregnancy: There are insufficient human data on the use of RUKOBIA during pregnancy to definitively assess a drug-associated risk for birth defects and miscarriage. An Antiretroviral Pregnancy Registry has been established.
- Lactation: Breastfeeding is not recommended due to the potential for HIV-1 transmission, developing viral resistance, and adverse reactions in a breastfed infant.
For more information please see US Prescribing Information for Rukobia.
About ViiV Healthcare
ViiV Healthcare is a global specialist HIV company established in November 2009 by GSK and Pfizer dedicated to delivering advances in treatment and care for people living with HIV and for people who are at risk of becoming infected with HIV. Shionogi joined as shareholders in October 2012. The company’s aims are to take a deeper and broader interest in HIV and AIDS than any company has done before and take a new approach to deliver effective and innovative medicines for HIV treatment and prevention, as well as support communities affected by HIV.
For more information on the company, its management, portfolio, pipeline, and commitment, please visit www.viivhealthcare.com.
About GSK
GSK is a global biopharma company with a purpose to unite science, technology and talent to get ahead of disease together. Find out more at gsk.com/company.
| ViiV Healthcare enquiries: | |||
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| Rachel Jaikaran | +44 (0) 7909 002 403 | (London) | |
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| Media enquiries: | Tim Foley | +44 (0) 20 8047 5502 | (London) |
| Madeleine Breckon | +44 (0) 20 8047 5502 |
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(Washington DC) | |
| Lyndsay Meyer | +1 202 302 4595 |
(Washington DC) | |
| Analyst/Investor enquiries: | Nick Stone | +44 (0) 7717 618834 | (London) |
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| James Dodwell | +44 (0) 20 8047 2406 | (London) | |
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| Jeff McLaughlin | +1 215 751 7002 | (Philadelphia) | |
Cautionary statement regarding forward-looking statements
GSK cautions investors that any forward-looking statements or projections made by GSK, including those made in this announcement, are subject to risks and uncertainties that may cause actual results to differ materially from those projected. Such factors include, but are not limited to, those described in the Company's Annual Report on Form 20-F for 2021, GSK’s Q2 Results for 2022 and any impacts of the COVID-19 pandemic.
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References
- P. Leone et.al. VH3810109 (N6LS) Reduces Viremia Across a Range of Doses in ART-Naive Adults Living with HIV: Proof of Concept Achieved in the Phase IIa BANNER (207959, NCT04871113) Study. Presented at HIV Glasgow 2022.
- M. A. Marzinke et. al., Laboratory analysis of HIV infections in the Year 1 unblinded period of HPTN 083: injectable cabotegravir for PrEP in MSM and TGW. Presented at HIV Glasgow 2022.
- S. DeWit et. al. CARISEL: A Hybrid III Implementation Effectiveness Study of Implementation of Cabotegravir Plus Rilpivirine Long Acting (CAB+RPV LA) in EU Health Care Settings; Key Clinical and Implementation Outcomes by Implementation Arm. Presented at IDWeek 2022.
- V. Chounta et. al. Patient-reported outcomes after 152 weeks of HIV maintenance therapy with long-acting cabotegravir + rilpivirine in the phase 3b ATLAS-2M study. Presented at HIV Glasgow 2022.
- G. Pierone et. al. Suppressed Switch to DTG/3TC 2-Drug Regimen vs BIC- or DTG-Based 3-Drug Regimens. Presented at IDWeek 2022.
- J. Borch et. al. 6-Month outcomes of every 2-months long-acting cabotegravir and rilpivirine in a real-world setting – effectiveness, adherence to injections and patient reported outcomes from PLHIV in the German CARLOS cohort. Presented at HIV Glasgow 2022.
- J. Scherzer et. al. The implementation of every 2-months cabotegravir and rilpivirine long-acting injections from the perspective of healthcare providers in the German CARLOS cohort, 6-month outcomes. Presented at HIV Glasgow 2022.
- R. Hsu US Healthcare Provider Perspectives on the Initiation of Cabotegravir and Rilpivirine Long-Acting (CAB+RPV LA) in an Observational Real-world Study (BEYOND). Presented at IDWeek 2022.
Media contacts
For our corporate press office, email: Rachel Jaikaran
OR call +44 7823 523 755
For US-specific media enquiries, email: Audrey Abernathy
OR call +1 919 605 4521
If you get any side effects, talk to your doctor, pharmacist, or nurse. This includes any possible side effects not listed in the package leaflet. You can also report side effects directly via the GSK Reporting Tool link https://gsk.public.reportum.com/. By reporting side effects, you can help provide more information on the safety of this medicine.
If you are from outside the UK, you can report adverse events to GSK/ ViiV by selecting your region and market, here.
