While drug-susceptible tuberculosis (TB) disease in children currently requires four to six months of treatment, most children may be able to be cured with a shorter treatment of more powerful drugs. Shorter treatment may be easier for children to tolerate and finish as well as ease caregiver strain from managing treatment side effects and supporting children over many months. The primary objective of this study is to evaluate if a 2-month regimen (including isoniazid (H), rifapentine (P), pyrazinamide (Z) and moxifloxacin (M)) is as safe and effective as a 4- to 6-month regimen (isoniazid, rifampicin (R), pyrazinamide, ethambutol (E)) in curing drug-susceptible TB disease in children under 10 years old. The study is also evaluating the safety of the HPZM in children with and without HIV.

Start Date30 Sep 2024

Sponsor / Collaborator

The Johns Hopkins University

NCT06281834 / Not yet recruitingPhase 1IIT

Dolutegravir Pharmacokinetics During Weekly Rifapentine/Isoniazid for TB Prevention

Tuberculosis (TB) is the leading cause of death among children living with HIV, yet insufficient data are available on the pharmacokinetics of newer TB prevention strategies in children. Short-course TB prevention/latent TB infection (LTBI) treatment regimens increase completion rates but have not been adequately studied among children living with HIV. Our prospective, open-label PK study will examine and extend use of weekly rifapentine and isoniazid (3HP) among children receiving dolutegravir. This will address gaps in knowledge by examining two-way PK of short-course LTBI treatment in a vulnerable pediatric population.

Start Date01 May 2024

Sponsor / Collaborator

The Brigham & Women's Hospital, Inc.

[+1]

NCT05021731 / Not yet recruitingPhase 4IIT

Comparison of 3-month Once-weekly Isoniazid Plus Rifapentine, 4-month Daily Rifampicin, and 3-month Daily Isoniazid Plus Rifampicin for the Treatment Latent Tuberculosis in Patients With End-stage Kidney Disease: A Randomised Clinical Trial

Objective To determine if treatment completion with a 4-month rifampin (4R) or 3-month rifapentine (P) + isoniazid (H) weekly for 12 weeks (3HP) regimens is better than with a 3-month (3HR) regimen for treatment of latent tuberculosis (TB) infection (LTBI) in patients with end stage kidney disease.
Methods Design: Multicenter, prospective, parallel-group, open-label, controlled clinical trial.
Study population: All adult patients with ESKD in who treatment for LTBI is prescribed at 7 hospitals.
Interventions: Patients who accept participation, will be randomly assigned to one of the 3 arms: 3HR (control) (90 doses), 4R (120 doses) or 3HP (12 doses).
Outcome: Proportion of participants who discontinue permanently the assigned treatment. Follow-up: Periodic assessment for permanent or temporary discontinuation, and adverse events of the assigned treatment.
Sample size: 225 subjects (75 per arm) will be needed to demonstrate, if exists, a 0.16 decrease in permanent discontinuation rates in the experimental arms (4R and 3HP) with respect to the control arm (3HR), with α= 0.025, β= 0.20, and 5% expected losses, and assuming a 0.25 proportion of permanent discontinuation in the control.

Start Date20 Apr 2024

Sponsor / Collaborator

Instituto De SAlud Carlos Iii De Madrid

[+1]

100 Clinical Results associated with Rifapentine

100 Translational Medicine associated with Rifapentine

100 Patents (Medical) associated with Rifapentine

588

Literatures (Medical) associated with Rifapentine

01 Feb 2024·The Lancet. Infectious diseases

Child-friendly rifapentine formulation is a game changer

Article

Author: Holt, Ed

31 Dec 2023·Emerging microbes & infections

Tuberculosis preventive treatment among individuals with inactive tuberculosis suggested by untreated radiographic abnormalities: a community-based randomized controlled trial

Article

Author: Zhang, Zhanjiang ; Du, Jiang ; Feng, Boxuan ; Wang, Dakuan ; Pan, Shouguo ; Guan, Xueling ; Guan, Ling ; Cao, Xuefang ; Jin, Qi ; Liu, Zisen ; Zhang, Bin ; Yan, Jiaoxia ; He, Yongpeng ; Shen, Fei ; Xin, Henan ; Zhang, Haoran ; He, Yijun ; Liu, Jianmin ; Du, Ying ; Gao, Lei

Epidemiological and interventional studies have been rarely conducted among those with positive interferon-γ release assay (IGRA) results and radiologically inactive tuberculosis (TB) lesions on chest radiograph. This study aimed to estimate the effectiveness and safety of a six-week twice-weekly regimen (rifapentine plus isoniazid) among this key population in rural China. First, chest digital radiography was conducted to screen individuals with inactive TB lesions. Then, the identified participants were further evaluated and eligible participants with IGRA-positive results were included in subsequent randomized controlled trial (RCT). Of 44,500 recruited residents, 2,988 presented with radiographically inactive TB among 43,670 with complete results of chest radiography and questionnaire, and 28.61% (855/2,988) tested IGRA positive. Subsequently, 677 eligible participants were included in this RCT (345 in the preventive treatment group and 332 in the untreated control group). The treatment completion rate was 80.00% (276/345), and 11.88% (41/345) participants reported side-effects including two cases of hepatotoxicity (0.58%, 2/345). In the intention-to-treat analysis, the cumulative incidence rate of microbiologically confirmed active TB during a two-year follow-up was 1.16 (95% confidence interval [CI]: 0.03-2.29) in the preventive treatment group and 1.51 (95% CI: 0.20-2.82) in the control group (p = .485). Subgroup analyses showed that the protective rates were 55.42% (95% CI: 10.33-93.07%) and 80.17% (95% CI: 25.36-97.96%) for participants with fibrosis and for those aged ≥60 years, respectively. The expected treatment effect was not observed for the six-week regimen in this study. Future studies with sufficient sample size are needed to verify our findings.

15 Dec 2023·Journal of acquired immune deficiency syndromes (1999)

Pharmacokinetics, Safety, and Tolerability of Once-Daily Darunavir With Cobicistat and Weekly Isoniazid/Rifapentine

Article

Author: Kumar, Parag ; George, Jomy M ; Adeojo, Lilian ; Swaim, Doris ; Kovacs, Joseph A ; Brooks, Kristina M ; Bunn, Haden T ; Peloquin, Charles A ; Pau, Alice K

Background::

Once-weekly isoniazid with rifapentine (HP) for 3 months is a recommended treatment for latent tuberculosis infection in persons with HIV. HP reduces exposures of certain antiretroviral medications, resulting in limited options for the concomitant use of these therapies. Here, we examined the pharmacokinetics (PK), safety, and tolerability of darunavir/cobicistat with HP.

Methods::

This was an open-label, fixed sequence, two-period crossover study in persons without HIV. Participants received darunavir 800 mg/cobicistat 150 mg once-daily alone for 4 days, then continued darunavir/cobicistat once-daily for days 5–19 with HP coadministration on days 5, 12, and 19. Intensive PK assessments were performed on days 4, 14, and 19. PK parameters were determined using noncompartmental methods. Geometric mean ratios with 90% confidence intervals (CIs) were calculated and compared between phases using mixed-effects models.

Results::

Thirteen participants were enrolled. Two withdrew after day 4, and one withdrew after day 14. Of the 3 withdrawals, 2 were attributed to drug-related adverse events. Darunavir area under the concentration–time curve, maximum concentrations (Cmax), and concentrations at 24 hours postdose (C24h) were reduced by 71%, 41%, and 96% ∼48–72 hours after HP administration (day 14), respectively, and 36%, 17%, and 89% with simultaneous HP administration (day 19), respectively. On day 14, 45% of the predose and 73% of C24h concentrations were below the darunavir EC50 (0.055 µg/mL).

Conclusions::

Darunavir exposures were significantly decreased with HP coadministration. Temporal relationships between HP coadministration and the extent of induction or mixed inhibition/induction of darunavir metabolism were apparent. Coadministration of darunavir/cobicistat with 3HP should be avoided.

News (Medical) associated with Rifapentine

28 Mar 2024

·www.biospace.com

FDA Expands Indication for Gilead's Vemlidy (Tenofovir Alafenamide) to Treat Chronic HBV Infection in Pediatric Patients as Young as Six

Efficacy and Safety Pro Once-Daily Vemlidy Demonstrated in Children Six Years of Age (Weighing at Least 25kg) and Older FOSTER CITY, Calif.--(BUSINESS WIRE)-- Gilead Sciences, Inc. (Nasdaq: GILD) today announced that the U.S. Food and Drug Administration (FDA) has approved the supplemental new drug application (sNDA) for Vemlidy® (tenofovir alafenamide) 25 mg tablets as a once-daily treatment for chronic hepatitis B virus (HBV) infection in pediatric patients six years of age and older and weighing at least 25 kg with compensated liver disease. Vemlidy is a targeted prodrug of tenofovir that was approved by the FDA in 2016 as a once-daily treatment for adults with chronic HBV infection with compensated liver disease. In 2022, the FDA approved Vemlidy for the treatment of chronic HBV infection in pediatric patients 12 years of age and older with compensated liver disease. Vemlidy is recommended as a preferred or first-line treatment for adults with chronic HBV with compensated liver disease by the American Association for the Study of Liver Diseases (AASLD) and European Association for the Study of the Liver (EASL) guidelines. “Chronic hepatitis B can have a significant and lasting impact on the health of children. If left untreated, hepatitis B can lead to liver cirrhosis and liver cancer,” said Chaun-Hao Lin, MD, Associate Professor of Clinical Pediatrics Krek School of Medicine of USC. “As a clinician, I am well aware of the critical importance of promptly treating this disease to avoid possible complications and liver damage. The clinical trial demonstrated that tenofovir alafenamide may represent an effective treatment option for children as young as six years old affected by this chronic disease.” Vemlidy’s approval in this pediatric patient population is supported by Week 96 data from a Phase 2 clinical trial (Trial 1092) comparing treatment with Vemlidy 25 mg to placebo among 18 treatment-naïve and treatment-experienced patients aged 6 to less than 12 years weighing at least 25 kg (Cohort 2, Group 1). Participants in the Vemlidy group and in the placebo group who switched to open-label Vemlidy after Week 24 demonstrated progressive increases in the rates of virological suppression through Week 96 overall and within both study cohorts (children and adolescents). “The expanded indication for Vemlidy for the treatment of children as young as six years old is a testament to the safety, tolerability and efficacy pro this therapy,” said Frank Duff, MD, Senior Vice President, Virology Therapeutic Area Head, Gilead Sciences. “Effective and tolerable options for children require our best science and a dedicated focus. The work of our Gilead Pediatric Center of Excellence is responsible for coordinating pediatric clinical trials for treatments for cancer, HIV, hepatitis B, and COVID-19 and we will continue our research to help address unmet treatment needs for children.” Vemlidy has a boxed warning in its product label regarding post-treatment severe acute exacerbation of hepatitis B. See below for important safety information. U.S. IMPORTANT SAFETY INFORMATION AND INDICATION FOR THE USE OF VEMLIDY BOXED WARNING: POSTTREATMENT SEVERE ACUTE EXACERBATION OF HEPATITIS B Discontinuation of anti-hepatitis B therapy, including VEMLIDY, may result in severe acute exacerbations of hepatitis B. Hepatic function should be monitored closely with both clinical and laboratory follow-up for at least several months in patients who discontinue anti-hepatitis B therapy, including VEMLIDY. If appropriate, resumption of anti-hepatitis B therapy may be warranted. Warnings and Precautions Risk of Development of HIV-1 Resistance in HBV/HIV-1 Coinfected Patients: Due to this risk, VEMLIDY alone should not be used for the treatment of HIV-1 infection. Safety and efficacy of VEMLIDY have not been established in HBV/HIV-1 coinfected patients. HIV antibody testing should be offered to all HBV-infected patients before initiating therapy with VEMLIDY, and if positive, an appropriate antiretroviral combination regimen that is recommended for HBV/HIV-1 coinfected patients should be used. New Onset or Worsening Renal Impairment: Postmarketing cases of renal impairment, including acute renal failure, proximal renal tubulopathy (PRT), and Fanconi syndrome, have been reported with TAF-containing products. Patients with impaired renal function and/or taking nephrotoxic agents (including NSAIDs) are at increased risk of renal-related adverse reactions. Discontinue VEMLIDY in patients who develop clinically significant decreases in renal function or evidence of Fanconi syndrome. Monitor renal function in all patients – See Dosage and Administration. Lactic Acidosis and Severe Hepatomegaly with Steatosis: Fatal cases have been reported with the use of nucleoside analogs, including tenofovir disoproxil fumarate (TDF). Discontinue VEMLIDY 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 Most common adverse events in the week 96 pediatric population reported in ≥5% were: nasopharyngitis, headache, COVID-19, pyrexia, diarrhea, upper respiratory tract infection, cough, respiratory tract infection viral, abdominal pain upper. Overall, abdominal pain upper and metabolic nephropathy were the only study drug–related adverse events, which occurred in > 1 participant, reported in 2.3% (2/88 participants) each. Drug Interactions Coadministration of VEMLIDY with drugs that reduce renal function or compete for active tubular secretion may increase concentrations of tenofovir and the risk of adverse reactions. Coadministration of VEMLIDY is not recommended with the following: oxcarbazepine, phenobarbital, phenytoin, rifabutin, rifampin, rifapentine, or St. John’s wort. Such coadministration is expected to decrease the concentration of tenofovir alafenamide, reducing the therapeutic effect of VEMLIDY. Drugs that strongly affect P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) activity may lead to changes in VEMLIDY absorption. Coadministration of VEMLIDY with carbamazepine, the tenofovir alafenamide dose should be increased to two tablets once daily. Consult the full prescribing information for VEMLIDY for more information on potentially significant drug interactions, including clinical comments. Dosage and Administration Testing Prior to Initiation: HIV infection. Prior to or When Initiating, and During Treatment: On a clinically appropriate schedule, assess serum creatinine, estimated creatinine clearance, urine glucose, and urine protein in all patients. In patients with chronic kidney disease, also assess serum phosphorus. Dosage: 1 tablet taken once daily with food. Renal Impairment: Not recommended in patients with end-stage renal disease (ESRD; eCrCl <15 mL/min) who are not receiving chronic hemodialysis; in patients on chronic hemodialysis, on hemodialysis days, administer VEMLIDY after completion of hemodialysis treatment. No data are available to make dose recommendations in pediatric patients with renal impairment. Hepatic Impairment: Not recommended in patients with decompensated (Child-Pugh B or C) hepatic impairment. Indication VEMLIDY is indicated for the treatment of chronic hepatitis B virus infection in adults and pediatric patients six years of age and older and weighing at least 25 kg with compensated liver disease. About the 1092 Study Study 1092 is an ongoing Phase 2 clinical trial that randomized 88 treatment-naïve and treatment-experienced patients with chronic hepatitis B infection between the ages of 12 to less than 18 years weighing at least 35 kg to receive either Vemlidy 25 mg (N=47) or placebo (N=23) and 6 to less than 12 years weighing at least 25 kg to receive either Vemlidy 25 mg (N = 12) or placebo (N=6) once daily. The study met its primary endpoint of percentage of patients with HBV DNA levels below 20 IU/mL at 24 weeks of therapy; overall, 19% (11/59) of patients treated with Vemlidy 25 mg achieved HBV DNA < 20 IU/mL at Week 24 compared to 0% (0/23) of patients treated with placebo. The overall percentage of patients with HBV DNA < 20 IU/mL progressively increased in the Vemlidy 25 mg group relative to the Week 24 time point at both Week 48 (37% [22/59 subjects]) and Week 96 (61.0% [36/59 subjects]). The overall median change from baseline in ALT values for the Vemlidy and placebo-Vemlidy treatment groups, respectively, was -39.5 U/L and -46.5 U/L at Week 96. At 96 weeks, ALT normalization (AASLD criteria) was achieved for 54% of Vemlidy-treated patients and 57% of patients who switched from placebo to Vemlidy. Serum ALT is an enzyme used to monitor liver damage. Importantly, the mean percent changes in bone mineral density from baseline to Week 24 were similar for Vemlidy-treated patients and placebo-treated patients (1.6% (N=48) and 1.9% (N=23) for lumbar spine, and 1.9% (N=50) and 2.0% (N=23) for whole body, respectively). At Week 24, mean changes from baseline BMD Z-scores were 0.01 and -0.07 for the lumbar spine, and -0.04 and -0.04 for whole body, for Vemlidy and placebo groups, respectively. About Hepatitis B Hepatitis B (HBV) is a serious disease that attacks the liver and can cause chronic (lifelong) infection, cirrhosis of the liver, liver cancer, and death in up to a third of patients. Hepatitis B is spread through infected blood or body fluids, sexual contact, injection drug use, or perinatally from mother to child. Early symptoms may include loss of appetite, fever, generalized aches and pains, fatigue, itching, urticaria (hives), and joint pain. The disease is often asymptomatic, which may lead to undiagnosed individuals. Later symptoms may include nausea and vomiting, halitosis (bad breath), dark brown urine, jaundice (yellowing of the skin and eyes), and right-sided abdominal pain (especially with external pressure or palpitation). About Gilead Sciences in Liver Disease For more than 20 years, Gilead has sought to address some of the biggest challenges in liver disease. The company has transformed the trajectory of multiple liver diseases through a relentless pursuit of innovation and pioneering access programs to bring meaningful therapies to people around the world. More work is required, and Gilead is committed to advancing innovative therapeutics to address the most pressing unmet needs in liver disease and overcoming barriers to better care. About Gilead Sciences Gilead Sciences, Inc. is a biopharmaceutical company that has pursued and achieved breakthroughs in medicine for more than three decades with the goal of creating a healthier world for all people. The company is committed to advancing innovative medicines to prevent and treat life-threatening diseases, including HIV, viral hepatitis, COVID-19 and cancer. Gilead operates in more than 35 countries worldwide, with headquarters in Foster City, California. Forward-Looking Statements This press release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 that are subject to risks, uncertainties, and other factors, including Gilead’s ability to initiate, progress or complete clinical trials or studies within currently anticipated timelines or at all, and the possibility of unfavorable results from ongoing and additional clinical trials or studies, including those involving Vemlidy; the risk that physicians may not see the benefits of prescribing Vemlidy for the treatment of chronic HBV in pediatric patients; and any assumptions underlying any of the foregoing. These risks, uncertainties, and other factors could cause actual results to differ materially from those referred to in the forward-looking statements. All statements other than statements of historical fact are statements that could be deemed forward-looking statements. The reader is cautioned that any such forward-looking statements are not guarantees of future performance and is cautioned not to place undue reliance on these forward-looking statements. These and other risks are described in detail in Gilead’s Annual Report on Form 10-K for the year ended December 31, 2023, as filed with the U.S. Securities and Exchange Commission. All forward-looking statements are based on information currently available to Gilead, and Gilead assumes no obligation and disclaims any intent to update any such forward-looking statement. U.S. Prescribing Information for Vemlidy, including BOXED WARNINGS, is available at Vemlidy, Gilead, and the Gilead logo are registered trademarks of Gilead Sciences, Inc., or its related companies. For more information about Gilead, please visit the company’s website at , follow Gilead on Twitter (@GileadSciences), or call Gilead Public Affairs at 1-800-GILEAD-5 or 1-650-574-3000. View source version on businesswire.com: Contacts Meaghan Smith, Media public_affairs@gilead.com Jacquie Ross, Investors investor_relations@gilead.com Source: Gilead Sciences, Inc. View this news release online at:

Clinical ResultDrug ApprovalPhase 2

06 Mar 2024

·www.businesswire.com

ViiV Healthcare Announces Interim Data at CROI Indicating Superior Efficacy of Long-Acting Injectable HIV Treatment Cabenuva (Cabotegravir + Rilpivirine) Compared to Daily Oral Therapy in Individuals Living With HIV Who Have Adherence Challenges

LONDON--( BUSINESS WIRE )--ViiV Healthcare, the global specialist HIV company majority owned by GSK, with Pfizer Inc. and Shionogi Limited as shareholders, today announced data from a planned interim analysis of the LATITUDE phase III trial, indicating that their long-acting injectable antiretroviral treatment (ART) for HIV, Cabenuva (cabotegravir + rilpivirine), demonstrated superior efficacy in maintaining viral load suppression compared to daily oral therapy in individuals with a history of ART adherence challenges. The data were presented by the Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections (ACTG) network at the Conference on Retroviruses and Opportunistic Infections (CROI 2024) , in Denver, Colorado. Kimberly Smith, MD, MPH, Head of Research & Development at ViiV Healthcare, said: “It’s estimated that one-third of people living with HIV in the United States struggle with maintaining viral suppression. The findings of the LATITUDE study show that long-acting injectable cabotegravir + rilpivirine could be important for some people in this group, giving them another option to help keep their virus under control and improve their health. Further, since we know that individuals whose virus is undetectable don’t transmit to sexual partners, this could be an important contribution to ending the HIV epidemic.” LATITUDE is a phase III, randomised, open-label study. Participants received comprehensive and incentivised adherence support while taking guideline-recommended, three-drug regimen oral ART, including dolutegravir and bictegravir-based regimens, to achieve viral suppression. Those who achieved viral suppression were eligible to randomise to staying on oral standard of care (SOC) regimens or switch to long-acting injectable cabotegravir + rilpivirine (LA-ART) dosed monthly. During the randomised phase of the study, 146 participants received monthly LA-ART and 148 continued on SOC. The primary endpoint was a comparison of regimen failure, defined as a combination of virologic failures (VF) and regimen discontinuations, between arms. 24.1% of participants on LA-ART experienced regimen failure compared to 38.5% on SOC {difference -14.4 (98.75% CI–29.8%, -0.8%)}. Although the primary endpoint did not meet the strict predefined stopping criterion for the interim analysis, key secondary endpoints of virologic failure (7.2% LA-ART vs. 25.4% SOC {difference -18.2% (98.75% CI-31.1%, -5.4%}) and treatment-related failure (9.6% LA-ART vs. 26.2% SOC {difference -16.6% (98.75% CI-29.9%, -3.3%)} favoured the LA-ART regimen. The study’s Data Safety Monitoring Board (DSMB) considered the totality of all the study endpoints together and concluded that the evidence indicated superior efficacy of long-acting ART over daily oral standard of care. The DSMB recommended that all eligible participants should be offered long-acting injectable cabotegravir + rilpivirine. The rate of adverse events (AEs) was similar in both arms. Three participants in the LA-ART arm had serious injection site reactions (ISR) and one participant discontinued due to an ISR. Two confirmed virologic failures in each arm had new resistance associated mutations (RAMS), including at least two new integrase inhibitor RAMs in both LA-ART participants. The LATITUDE (Long-Acting Therapy to Improve Treatment Success in Daily Life) study is ongoing across 31 sites in the U.S. including Puerto Rico, implemented through ACTG. The median age of study participants was 40 years old; 40 percent of participants were male, 64 percent were Black/African American, 17 percent were Hispanic, 5 percent were transgender, and 14 percent currently or previously used injection drugs. The study is sponsored and funded by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, and is being conducted by ACTG, with additional support from the National Institute of Mental Health, the National Institute on Drug Abuse, ViiV Healthcare and the Janssen Pharmaceutical Companies of Johnson & Johnson. About Cabenuva (cabotegravir + rilpivirine) Cabenuva is indicated as a complete regimen for the treatment of HIV-1 infection in adults to replace the current antiretroviral regimen in those who are virologically suppressed (HIV-1 RNA <50 c/ml) on a stable antiretroviral regimen with no history of treatment failure and with no known or suspected resistance to either cabotegravir or rilpivirine. The complete regimen combines the integrase strand transfer inhibitor (INSTI) cabotegravir, developed by ViiV Healthcare, with rilpivirine, a non-nucleoside reverse transcriptase inhibitor (NNRTI) developed by Janssen Sciences Ireland Unlimited Company. Rilpivirine tablets are approved in the US as a 25mg tablet taken once a day to treat HIV-1 in combination with other antiretroviral agents in antiretroviral treatment-naïve patients 12 years of age and older and weighing at least 35kg with a viral load ≤100,000 HIV RNA c/ml. INSTIs inhibit HIV replication by preventing the viral DNA from integrating into the genetic material of human immune cells (T-cells). This step is essential in the HIV replication cycle and is also responsible for establishing chronic disease. Rilpivirine is an NNRTI that works by interfering with an enzyme called reverse transcriptase, which stops the virus from multiplying. Trademarks are owned by or licensed to the ViiV Healthcare group of companies. Please consult the full Prescribing Information. CABENUVA (cabotegravir; rilpivirine) extended-release injectable suspensions Professional Indication and Important Safety Information 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 About ACTG ACTG is the world’s largest and longest running clinical trials network focused on HIV and other infectious diseases and the people living with them. It is funded by NIAID and collaborating NIH Institutes. Founded in 1987, ACTG conducts research to improve the management of HIV and its comorbidities; develop a cure for HIV; and innovate treatments for tuberculosis, hepatitis B, and emerging infectious diseases. It comprises thousands of dedicated researchers, staff, and community members who are pursuing research into novel treatments and cures for infectious diseases at hundreds of locations across four continents, with the ultimate goal of advancing science that meaningfully impacts the lives of the people we serve. About ViiV Healthcare ViiV Healthcare is a global specialist HIV company established in November 2009 by GSK (LSE: GSK) and Pfizer (NYSE: PFE) dedicated to delivering advances in treatment and care for people living with HIV and for people who are at risk of acquiring HIV. Shionogi became a ViiV shareholder 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 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. 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 under Item 3.D “Risk factors” in the company's Annual Report on Form 20-F for 2023. Registered in England & Wales: GSK plc No. 3888792 ViiV Healthcare Limited No. 06876960 Registered Office: GSK plc 980 Great West Road Brentford, Middlesex United Kingdom TW8 9GS ViiV Healthcare Limited GSK Medicines Research Centre Gunnels Wood Road, Stevenage United Kingdom SG1 2NY

Phase 3Clinical ResultDrug Approval

28 Feb 2024

·www.biospace.com

ViiV Healthcare to present data for its next generation of ultra long-acting treatments for HIV

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 Number Presentation Dolutegravir A single once-daily ABC/DTG/3TC tablet predicts safe and effective exposures in children 3 to <6kg H. Chandasana 02770 Poster Tuesday, March 5 2:30-4:00pm MST Population pharmacokinetics of ABC/DTG/3TC FDC to support dosing in peds with HIV-1 (IMPAACT 2019) H. Chandasana 03110 Poster Tuesday, March 5:30-4:00pm MST Dolutegravir and growth in pediatric populations with HIV-1: IMPAACT P1093 and IMPAACT 2019 M. McKenna 01783 Poster Tuesday, March 5 2:30-4:00pm MST Switching to DTG+3TC vs 3-drug regimens in routine clinical care: long-term Swedish data E. Sörstedt 01838 Poster Tuesday, March 5 2:30-4:00pm MST Temporal trends of cardiovascular disease incidence in people with HIV from 2001-2021 N. Jaschinski 02263 Poster Tuesday, March 5 2:30-4:00pm MST Increased cancer risk with low CD4 counts persists despite over 2 years of virological suppression J. Hoy 01462 Poster Wednesday, March 6 2:30-4:00pm MST Cabotegravir for Treatment Long-acting Injectable CAB/RPV is Superior to Oral ART in PWH with adherence challenges: ACTG A5359 A. Rana 03579 Oral Wednesday, March 6 12:51-1:00pm MST Real-world utilization of cabotegravir + rilpivirine in the US: data from Trio Health cohort J. J. Eron 01374 Poster Monday, March 4 2:30-4:00pm MST Real-world effectiveness of cabotegravir + rilpivirine vs. standard of care oral regimens in the US R. K. Hsu 01952 Poster Monday, March 4 2:30-4:00pm MST HIV-1 RNA blips and low-level viral replication: SOLAR (CAB+RPV LA vs. BIC/FTC/TAF) C. Latham 00138 Poster Monday, March 4 2:30-4:00pm MST Model based comparison of cabotegravir pharmacokinetics following thigh and gluteal injections K. Han 03157 Poster Wednesday, March 6 2:30-4:00pm MST Cabotegravir for PrEP SEARCH Randomized trial of Dynamic Choice HIV Prevention including injectable cabotegravir (CAB-LA) J. Kabami 03405 Late-Breaker Oral Tuesday, March 5 10:00-12:00pm MST Pre-exposure prophylaxis with cabotegravir long-acting injectable in the OPERA cohort A. Mills 01400 Poster Monday, March 4 2:30-4:00pm MST Real-world use of cabotegravir long acting for pre-exposure prophylaxis: TRIO cohort K. Mayer 01907 Poster Monday, March 4 2:30-4:00pm MST Cabotegravir PopPK analysis of adults and adolescents living with HIV or at risk for HIV receiving PrEP Y. Lin 03038 Poster Tuesday, March 5 2:30-4:00pm MST Interest in long-acting injectable PrEP among transgender women in the United States E. E. Cooney 00621 Poster Wednesday, March 6 2:30-4:00pm MST Healthcare staff acceptability and feasibility of telehealth delivery of cabotegravir for PrEP A. Liu 03080 Poster Wednesday, March 6 2:30-4:00pm MST Fostemsavir Temsavir treatment enhances bNAb recognition and subsequent clearance of HIV-1 infected cells R. Ferris 02971 Poster Monday, March 4 2:30-4:00pm MST Pipeline: Ultra Long-Acting Cabotegravir Phase I study of cabotegravir long-acting injectable formulations supports ≥4-monthly dose interval K. Han 00251 Oral Monday, March 4 10:00-12:00pm MST Pipeline: Broadly Neutralising Antibodies VH3810109 (N6LS) in antiretroviral therapy–naive adults with HIV-1: phase IIa BANNER efficacy data P. Leone 01911 Oral Monday, March 4 10:00-12:00pm MST Safety and efficacy of VRC07-523LS plus long-acting cabotegravir in the phase 2 ACTG A5357 Trial B. Taiwo 02254 Oral Monday, March 4 10:00-12:00pm MST High-dose VH3810109 (N6LS) ± recombinant human hyaluronidase PH20: phase I SPAN study safety results B. Win 01988 Poster Wednesday, March 6 2:30-4:00pm MST Pipeline: Maturation Inhibitors Next-generation maturation inhibitor GSK3640254 showed broad spectrum potency without MI resistance B. McAuliffe 03095 Poster Wednesday, March 6 2:30-4:00pm MST The preclinical pro maturation inhibitor VH3739937 J. Jeffrey 02819 Poster Wednesday, March 6 2:30-4:00pm MST General HIV Resistance in young children newly diagnosed with HIV in Western Cape, South Africa K. Anderson 01012 Poster Tuesday, March 5 2:30-4:00pm MST 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: https://gskpro.com/content/dam/global/hcpportal/en_US/Prescribing_Information/Dovato/pdf/DOVATO-PI-PIL.PDF 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. 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, diarrhea, 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 For more information, please see full US Prescribing Information for APRETUDE: RUKOBIA (fostemsavir) extended-release tablets INDICATION RUKOBIA, in combination with other antiretrovirals (ARVs), is indicated to treat HIV-1 infection in heavily treatment-experienced adults with multidrug-resistant HIV-1 infection failing their current ARV regimen due to resistance, intolerance, or safety considerations. IMPORTANT SAFETY INFORMATION 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 full US Prescribing Information for RUKOBIA: About ViiV Healthcare ViiV Healthcare is a global specialist HIV company established in November 2009 by GSK (LSE: GSK) and Pfizer (NYSE: PFE) dedicated to delivering advances in treatment and care for people living with HIV and for people who are at risk of acquiring HIV. Shionogi became a ViiV shareholder 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 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. 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 under Item 3.D “Risk factors” in the company's Annual Report on Form 20-F for 2022, and Q4 Results for 2023. Registered in England & Wales: GSK plc ViiV No. 3888792 Healthcare Limited No. 06876960 Registered Office: GSK plc 980 Great West Road Brentford, Middlesex United Kingdom TW8 9GS ViiV Healthcare Limited GSK Medicines Research Centre Gunnels Wood Road, Stevenage United Kingdom SG1 2NY References 1 Han, et al. Phase I Study of Cabotegravir Long-Acting Injectable Formulations Supports ≥4-Monthly Dose Interval. Presented at 31st Conference on Retroviruses and Opportunistic Infections (CROI). March 2024. 2 Leone, et al. VH3810109 (N6LS) in Antiretroviral Therapy–Naive Adults With HIV-1: Phase IIa BANNER Efficacy Data. Presented at 31st Conference on Retroviruses and Opportunistic Infections (CROI). March 2024. 3 Win, et al. High-Dose VH3810109 (N6LS) ± Recombinant Human Hyaluronidase PH20: Phase I SPAN Study Safety Results. Presented at 31st Conference on Retroviruses and Opportunistic Infections (CROI). March 2024. 4 Taiwo, et al. Safety and Efficacy of VRC07-523LS plus Long-Acting Cabotegravir in the Phase 2 ACTG A5357 Trial. Presented at 31st Conference on Retroviruses and Opportunistic Infections (CROI). March 2024. 5 Rana, et al. Long-acting Injectable CAB/RPV is Superior to Oral ART in PWH with adherence challenges: ACTG A5359. Presented at 31st Conference on Retroviruses and Opportunistic Infections (CROI). March 2024. 6 Kamya, et al. SEARCH Randomized trial of Dynamic Choice HIV Prevention including injectable cabotegravir (CAB-LA). Presented at 31st Conference on Retroviruses and Opportunistic Infections (CROI). March 2024. 7 Hsu, et al. Real-World Effectiveness of Cabotegravir + Rilpivirine vs. Standard of Care Oral Regimens in the US. Presented at 31 Conference on Retroviruses and Opportunistic Infections (CROI). March 2024. 8 Sörstedt, et al. Switching to DTG+3TC vs 3-drug regimens in routine clinical care: long-term Swedish data. Presented at 31st Conference on Retroviruses and Opportunistic Infections (CROI). March 2024. 9 Data on File

Phase 2Phase 1Clinical ResultPhase 3

100 Deals associated with Rifapentine

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KEGG	Wiki	ATC	Drug Bank
D00879	Rifapentine	J04AB05	DB01201

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Pulmonary Tuberculosis	US	Sanofi-Aventis U.S. LLC	22 Jun 1998
Tuberculosis	CN	Wuxi Fortune Pharmaceutical Co., Ltd.	01 Jan 1994

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Latent Tuberculosis	Phase 3	US	-	01 Jun 2001
Latent Tuberculosis	Phase 3	BR	-	01 Jun 2001
Latent Tuberculosis	Phase 3	CA	-	01 Jun 2001
Latent Tuberculosis	Phase 3	ES	-	01 Jun 2001
HIV Infections	Phase 2	ZA	Sanofi	12 Oct 2019
HIV Infections	Phase 2	ZA	University of Stellenbosch	12 Oct 2019
HIV Infections	Phase 2	ZA	The Johns Hopkins University	12 Oct 2019
HIV Infections	Phase 2	ZA	Chris Hani Baragwanath Hospital	12 Oct 2019
HIV Infections	Phase 2	ZA	University of Cape Town	12 Oct 2019

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03510468 (CTgov)	Phase 1	-	51	Pyridoxine+Tenofovir alafenamide+Rifapentine+Isoniazid (INH)	dsdlziuxmo(vnourlshwe) = chggxpfxma hzdixzlxgt (acgkahloij, vfftjttsby - lxbgzffram) View more	-	25 Oct 2023
S31/A5349 (Pubmed)	Phase 3	Pulmonary Tuberculosis	-	Rifapentine-moxifloxacin regimen	yrjyzxesbu(xargcmtvqd): absolute difference in unfavorable outcomes = -7.4 (95% CI, -20.8 to 6.0)	Positive	30 Aug 2022
				Control regimen
NCT02410772 (CTgov)	Phase 3	Pulmonary Tuberculosis	2,516	ethambutol+rifampin+Pyridoxine (vitamin B6)+isoniazid+pyrazinamide (Regimen 1 (2HRZE/4HR))	udmatcprpf(uarrunzmjj) = zxkvfhyuvq sgwujbudmp (lypgiyzakf, aujmithaom - wqxgvedmaw) View more	-	28 Sep 2021
				ethambutol+Rifapentine+rifampin+Pyridoxine (vitamin B6)+isoniazid+pyrazinamide (Regimen 2 (2HPZ/2HP))	udmatcprpf(uarrunzmjj) = aclizyudse sgwujbudmp (lypgiyzakf, aisgmeoqle - vzzbpdoaec) View more
NCT02410772 (Study 31, Pubmed \| Br Dent J)	Phase 3	Tuberculosis	2,516	4-month rifapentine-based regimen with moxifloxacin	tpowtuucuq(yteligngbn) = isjsjamypp nokmdjmpio (jiopwuyyuc )	Positive	06 May 2021
				4-month rifapentine-based regimen without moxifloxacin	tpowtuucuq(yteligngbn) = vrijtabupu nokmdjmpio (jiopwuyyuc )
ERS2020	Not Applicable	Latent Tuberculosis Maintenance	88	Rifapentine plus isoniazid (3HP)	dpvgitycje(hlobwmbdam) = AST (aspartate aminotransaminase) elevation <2x upper limit were observed in both regimens hzolrzsrlm (mubvcxnxsh ) View more	Positive	07 Sep 2020
				Isoniazid (9H)
NCT02430259 (Pubmed \| Clin Microbiol Infect)	Phase 3	Silicosis	513	3RPT/INH	vhrkqvuirn(cfsypknwka) = fsekymbdka qptkyqyaxn (ptyvksbbin ) View more	-	15 Jun 2020
				rifapentine (Observation)	vhrkqvuirn(cfsypknwka) = fpsxppfyrd qptkyqyaxn (ptyvksbbin )
NCT01162486 (CTgov)	Phase 1	Pulmonary Tuberculosis	37	Rifampin & midazolam (Rifampin Control)	tofcrxuxra(sllmfnupxt) = aejkqsthnd qnbxprlxmr (qwpgjvqyod, ifdfuuzicu - nfwdteerof) View more	-	07 May 2019
				rifapentine & midazolam (RPT 1)	tofcrxuxra(sllmfnupxt) = wsdbcvikgd qnbxprlxmr (qwpgjvqyod, dsxomoodcj - tkzqwblzsw) View more
NCT01404312 (BRIEF TB, Pubmed) Manual	Phase 3	Tuberculosis	3,000	Rifapentine+Isoniazid (1-month group)	qbgwwsjemf(sokeubzpdx) = xtxttgzhpb sgkzemhroy (zozumamdas ) View more	Positive	14 Mar 2019
				Rifapentine+Isoniazid (9-month group)	qbgwwsjemf(sokeubzpdx) = idscdeldba sgkzemhroy (zozumamdas ) View more
NCT00728507 (CTgov)	Phase 2	Pulmonary Tuberculosis	121	HPZM (HPZM)	anhlyvbfno(dhgzzuzbuo) = cysiendlwv zqkjtxjisv (efxfeailqn, wyicufodzk - awctokermw) View more	-	20 Apr 2017
				ethambutol (HRZE)+Ethambutol+Rifampin+Pyridoxine (vitamin B6)+Isoniazid+Pyrazinamide (HRZE)	anhlyvbfno(dhgzzuzbuo) = vzlfxtyjkn zqkjtxjisv (efxfeailqn, sjrcpkhbxq - heemaaiaox) View more
NCT00814671 (CTgov)	Phase 2	Pulmonary Tuberculosis	153	Rifapentine 450 (RPT450)	nbppzuqrao(jxspgithyt) = odshdiibpi wpzgmtolks (bnxrzpzoke, uyveeqedru - cbbzwnqlov) View more	-	28 Sep 2016
				Rifampin (RIF 600)	nbppzuqrao(jxspgithyt) = nyiktinadz wpzgmtolks (bnxrzpzoke, qvcikmcbdh - cgpazaaere) View more

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