ViiV Healthcare to present data for its next generation of ultra long-acting treatments for HIV
February 28, 2024- Other key data to be presented from ViiV Healthcare’s innovative pipeline and portfolio include the exploration of different mechanisms of action through broadly neutralising antibodies as well as real-world insights from established long-acting and 2-drug regimens
LONDON–(BUSINESS WIRE)–ViiV Healthcare, the global specialist HIV company majority owned by GSK, with Pfizer and Shionogi as shareholders, today announced the presentation of 64 abstracts that includes highlights of the company’s next-generation pipeline advancements, alongside data from its diverse portfolio of marketed HIV treatment and prevention options at the Conference on Retroviruses and Opportunistic Infections (CROI 2024) being held in Denver, Colorado, from 3 – 6 March 2024.
Kimberly Smith, M.D., MPH, Head of Research & Development at ViiV Healthcare, said: “As leaders in developing long-acting injectables for the treatment of HIV, we’re excited to present new data setting the stage for ViiV’s next generation of medicines and demonstrating how key pipeline assets will target HIV in different ways. These findings, as well as the breadth of data we’ll present on our marketed products, including new interim results from the LATITUDE study, reflect a portfolio and future-looking pipeline focused on ending the HIV epidemic. We look forward to sharing them with the scientific and HIV communities at CROI 2024.”
Key abstracts to be presented at CROI 2024 by ViiV Healthcare and its study partners will include:
Data introducing our next generation of potential ultra long-acting medicines for HIV: ViiV Healthcare will share findings from a phase I study evaluating different formulations of cabotegravir and their potential for dosing every four months. The ongoing, open-label, single-dose, dose-escalation phase I study in 70 healthy adults assessed both the 200 mg/mL formulation of cabotegravir in combination with recombinant human hyaluronidase PH20 (rHuPH20), as well as a new formulation of cabotegravir (CAB ULA) administered by itself.1 Researchers will share safety and pharmacokinetic findings from both ultra long-acting approaches and their potential for future clinical development.
Findings advancing different mechanisms of action in HIV research: New phase IIa findings from the BANNER study of VH3810109 (N6LS), an investigational, broadly neutralising antibody (bNAb), will be presented. Researchers will share findings of the bNAb administered intravenously and the first efficacy findings of its subcutaneous administration.2 Findings from the SPAN study of N6LS, examining the safety and tolerability of the highest subcutaneous and intravenous N6LS doses administered to date, with and without PH20, will also be presented.3 Additionally, efficacy and safety data from a non-ViiV owned bNAb asset, VRC07-523LS, in a phase II, open-label clinical trial used in combination with long-acting CAB for maintenance antiretroviral therapy (ART) will be presented.4
New data on long-acting therapy vs daily oral standard of care, in traditionally non-adherent populations: Interim analysis of the LATITUDE phase III trial will be presented showing that, the injectable antiretroviral treatment for HIV, Cabenuva (cabotegravir and rilpivirine [CAB+RPV LA]), demonstrates superior efficacy compared to daily oral standard of care (SOC) in individuals with a history of antiretroviral adherence challenges. The NIAID/ACTG also announced a modification to the study, where further randomisation has been stopped and participants in the SOC arm are being given the option to switch to the long-acting therapy arm.5
Real-world evidence from across our treatment and prevention portfolios: New findings from SEARCH, a randomised study evaluating the real-world impact of the inclusion of long-acting cabotegravir for PrEP in an HIV prevention coverage package compared to the standard-of-care of oral PrEP and PEP alone in rural Uganda and Kenya, will also be presented.6 Real-world evidence findings for the complete long-acting HIV treatment regimen Cabenuva will be presented from the OPERA cohort examining ART-experienced, virally suppressed adults living with HIV who switched to CAB+RPV LA or to an oral regimen.7
Findings for the 2-drug regimen, Dovato (dolutegravir, lamivudine [DTG/3TC]), will include the InfCare HIV study, which presents three-year switch data, from 3-drug regimen to Dovato, in a long-term real-world Swedish cohort.8 This study adds to the body of real-world evidence to date that includes more than 40,000 people living with HIV.9
Here is a list of ViiV Healthcare-sponsored or supported studies to be presented at CROI 2024:
|
Title |
First Author |
Presentation |
Presentation |
|
Dolutegravir |
|||
|
A single once-daily ABC/DTG/3TC tablet predicts safe and effective exposures in children 3 to <6kg |
H. Chandasana |
02770 |
Poster |
|
Population pharmacokinetics of ABC/DTG/3TC FDC to support dosing in peds with HIV-1 (IMPAACT 2019) |
H. Chandasana |
03110 |
Poster |
|
Dolutegravir and growth in pediatric populations with HIV-1: IMPAACT P1093 and IMPAACT 2019 |
M. McKenna
|
01783 |
Poster |
|
Switching to DTG+3TC vs 3-drug regimens in routine clinical care: long-term Swedish data |
E. Sörstedt
|
01838 |
Poster |
|
Temporal trends of cardiovascular disease incidence in people with HIV from 2001-2021 |
N. Jaschinski |
02263 |
Poster |
|
Increased cancer risk with low CD4 counts persists despite over 2 years of virological suppression |
J. Hoy |
01462 |
Poster |
|
Cabotegravir for Treatment |
|||
|
Long-acting Injectable CAB/RPV is Superior to Oral ART in PWH with adherence challenges: ACTG A5359 |
A. Rana |
03579 |
Oral |
|
Real-world utilization of cabotegravir + rilpivirine in the US: data from Trio Health cohort |
J. J. Eron
|
01374 |
Poster |
|
Real-world effectiveness of cabotegravir + rilpivirine vs. standard of care oral regimens in the US |
R. K. Hsu |
01952 |
Poster |
|
HIV-1 RNA blips and low-level viral replication: SOLAR (CAB+RPV LA vs. BIC/FTC/TAF) |
C. Latham |
00138 |
Poster |
|
Model based comparison of cabotegravir pharmacokinetics following thigh and gluteal injections |
K. Han |
03157 |
Poster |
|
Cabotegravir for PrEP |
|||
|
SEARCH Randomized trial of Dynamic Choice HIV Prevention including injectable cabotegravir (CAB-LA) |
J. Kabami |
03405 |
Late-Breaker Oral |
|
Pre-exposure prophylaxis with cabotegravir long-acting injectable in the OPERA cohort |
A. Mills |
01400 |
Poster |
|
Real-world use of cabotegravir long acting for pre-exposure prophylaxis: TRIO cohort |
K. Mayer
|
01907 |
Poster |
|
Cabotegravir PopPK analysis of adults and adolescents living with HIV or at risk for HIV receiving PrEP |
Y. Lin
|
03038 |
Poster |
|
Interest in long-acting injectable PrEP among transgender women in the United States |
E. E. Cooney |
00621 |
Poster |
|
Healthcare staff acceptability and feasibility of telehealth delivery of cabotegravir for PrEP |
A. Liu |
03080 |
Poster |
|
Fostemsavir |
|||
|
Temsavir treatment enhances bNAb recognition and subsequent clearance of HIV-1 infected cells |
R. Ferris
|
02971 |
Poster |
|
Pipeline: Ultra Long-Acting Cabotegravir |
|||
|
Phase I study of cabotegravir long-acting injectable formulations supports ≥4-monthly dose interval |
K. Han |
00251 |
Oral |
|
Pipeline: Broadly Neutralising Antibodies |
|||
|
VH3810109 (N6LS) in antiretroviral therapy–naive adults with HIV-1: phase IIa BANNER efficacy data |
P. Leone |
01911 |
Oral |
|
Safety and efficacy of VRC07-523LS plus long-acting cabotegravir in the phase 2 ACTG A5357 Trial |
B. Taiwo |
02254 |
Oral |
|
High-dose VH3810109 (N6LS) ± recombinant human hyaluronidase PH20: phase I SPAN study safety results |
B. Win
|
01988 |
Poster |
|
Pipeline: Maturation Inhibitors |
|||
|
Next-generation maturation inhibitor GSK3640254 showed broad spectrum potency without MI resistance |
B. McAuliffe |
03095 |
Poster |
|
The preclinical profile of maturation inhibitor VH3739937 |
J. Jeffrey |
02819 |
Poster |
|
General HIV |
|||
|
Resistance in young children newly diagnosed with HIV in Western Cape, South Africa |
K. Anderson |
01012 |
Poster |
DOVATO (dolutegravir and 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 counseled on the consistent use of effective contraception
Lactic Acidosis and Severe Hepatomegaly With Steatosis:
Fatal cases have been reported with the use of nucleoside analogs, 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%), diarrhea (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: There are insufficient human data on the use of Dovato during pregnancy to definitively assess a drug-associated risk for birth defects and miscarriage. An Antiretroviral Pregnancy Registry has been established. Advise individuals of childbearing potential of the potential risk of neural tube defects. 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 or if pregnancy is confirmed in the first trimester
- Lactation: Breastfeeding is not recommended due to the potential for HIV-1 transmission, developing viral resistance in HIV-positive infants, and adverse reactions in a breastfed infant
- Females and Males of Reproductive Potential: Pregnancy testing is recommended before initiation of Dovato. Counsel individuals of childbearing potential taking Dovato on the consistent use of effective contraception
- 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)
For more information, please see full US Prescribing Information for Dovato:
CABENUVA (cabotegravir; rilpivirine) extended-release injectable suspensions
INDICATION
CABENUVA is indicated as a complete regimen for the treatment of HIV-1 infection in adults and adolescents 12 years of age and older and weighing at least 35 kg to replace the current antiretroviral regimen in those who are virologically suppressed (HIV-1 RNA <50 copies/mL) on a stable antiretroviral regimen with no history of treatment failure and with no known or suspected resistance to either cabotegravir or rilpivirine.
IMPORTANT SAFETY INFORMATION
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:
- Serious or severe hypersensitivity reactions have been reported in association with other integrase inhibitors and could occur with CABENUVA
- 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
- Discontinue CABENUVA immediately if signs or symptoms of hypersensitivity reactions develop. Clinical status, including liver transaminases, should be monitored and appropriate therapy initiated. Cabotegravir and rilpivirine oral lead-in may be used to help identify patients who may be at risk of a hypersensitivity reaction
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 accidental 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, suicide 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 in adults (incidence ≥2%, all grades) treated 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 (cabotegravir), or EDURANT (rilpivirine)
- 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 UGT1A9 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: Potential risks of breastfeeding include HIV-1 transmission, developing viral resistance in HIV-positive infants, and adverse reactions in a breastfed infant
For more information, please see full US Prescribing Information for Cabenuva:
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 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.
Contacts
ViiV Healthcare enquiries:
Media enquiries:
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(London)
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(Colorado)
GSK enquiries:
Media enquiries:
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(London)
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+1 202 603 5003
(Washington DC)
Lyndsay Meyer
+1 202 302 4595
(Washington DC)
Alison Hunt
+1 540 742 3391
(Washington DC)
Investor Relations:
Nick Stone
+44 (0) 7717 618834
(London
James Dodwell
+44 (0) 20 8047 2406
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Mick Readey
+44 (0) 7990 339653
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Josh Williams
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+44 (0) 7796 707505
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Jeff McLaughlin
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Frannie DeFranco
+1 215 751 4855
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