GSK PLC 
* Long-acting treatment enables people living with HIV to reduce the days they receive treatment from 365 to 12 or 6 per year after initiation
Data from one of the most extensive global HIV patient-reported outcomes studies, Positive Perspectives 2 sponsored by
An estimated 30,000 people are living with HIV in
About cabotegravir
Cabotegravir is an integrase strand transfer inhibitor (INSTI) developed by
INSTIs, like cabotegravir, 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 infection.
About rilpivirine and rilpivirine long-acting
The oral formulation of rilpivirine is also authorised for the treatment of HIV-1 infection 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 copies/mL.
Rilpivirine long-acting is a prolonged-release suspension for intramuscular injection developed by Janssen Sciences Ireland UC, one of the Janssen Pharmaceutical Companies of
Administration and dosing of cabotegravir and rilpivirine
Cabotegravir injection used in combination with rilpivirine injection is a complete long-acting regimen dosed once-monthly or once every 2-months for virologically suppressed people living with HIV-1. Cabotegravir and rilpivirine injections are administered as two intramuscular (IM) injections in the buttocks by a healthcare professional at the same appointment. Prior to the initiation of the injections, cabotegravir and rilpivirine oral tablets are taken for approximately one month (at least 28 days) to assess tolerability to the medicines.
For monthly dosing, the usual adult dosage is 600 mg of cabotegravir administered intramuscularly in the gluteal site with rilpivirine long-acting. Thereafter, 400 mg should be intramuscularly administered in the gluteal site monthly. For every two-month dosing, the usual adult dosage is 600 mg of cabotegravir administered intramuscularly in the gluteal site with rilpivirine long-acting. One month after the initial dosing of cabotegravir injection, 600 mg should be intramuscularly administered in the gluteal site. Thereafter, 600 mg should be intramuscularly administered in the gluteal site every two months.
Important Safety Information
The following Important Safety Information is based on the Summary of Product Characteristics for Vocabria. Please consult the full Summary of Product Characteristics for all the safety information.
Vocabria (cabotegravir) injection is indicated, in combination with rilpivirine injection, for the treatment of Human Immunodeficiency Virus type 1 (HIV-1) infection in adults who are virologically suppressed (HIV-1 RNA 65 years of age. No dose adjustment of EDURANT is required in older patients. EDURANT should be used with caution in this population.
Paediatric population: The safety and efficacy of EDURANT in children aged < 12 years have not yet been established. No data are available.
Contraindications
Hypersensitivity to the active substance or to any of the excipients.
EDURANT should not be co-administered with the following medicinal products, as significant decreases in rilpivirine plasma concentrations may occur (due to CYP3A enzyme induction or gastric pH increase), which may results in loss of therapeutic effect of EDURANT:
* the anticonvulsants carbamazepine, oxcarbazepine, phenobarbital, phenytoin
* the antimycobacterials rifampicin, rifapentine
* proton pump inhibitors, such as omeprazole, esomeprazole, lansoprazole, pantoprazole, rabeprazole
* the systemic glucocorticoid dexamethasone, except as a single dose treatment
*
Special Warnings and Precautions for Use
While effective viral suppression with antiretroviral therapy has been proven to substantially reduce the risk of sexual transmission, a residual risk cannot be excluded. Precautions to prevent transmission should be taken in accordance with national guidelines.
Virologic failure and development of resistance
EDURANT has not been evaluated in patients with previous virologic failure to any other antiretroviral therapy.
In the pooled efficacy analysis from the Phase III trials in adults through 96 weeks, patients treated with rilpivirine with a baseline viral load > 100,000 HIV-1 RNA copies/ml had a greater risk of virologic failure (18.2% with rilpivirine versus 7.9% with efavirenz) compared to patients with a baseline viral load <= 100,000 HIV-1 RNA copies/ml (5.7% with rilpivirine versus 3.6% with efavirenz). The greater risk of virologic failure for patients in the rilpivirine arm was observed in the first 48 weeks of these trials. Patients with a baseline viral load > 100,000 HIV-1 RNA copies/ml who experienced virologic failure 3exhibited a higher rate of treatment-emergent resistance to the non-nucleoside reverse transcriptase inhibitor (NNRTI) class. More patients who failed virologically on rilpivirine than who failed virologically on efavirenz developed lamivudine/emtricitabine associated resistance.
As with other antiretroviral medicinal products, resistance testing should guide the use of rilpivirine.
Cardiovascular
At supra-therapeutic doses (75 and 300 mg once daily), rilpivirine has been associated with prolongation of the QTc interval of the electrocardiogram (ECG). EDURANT at the recommended dose of 25 mg once daily is not associated with a clinically relevant effect on QTc. EDURANT should be used with caution when co-administered with medicinal products with a known risk of Torsade de Pointes.
Immune reactivation syndrome
In HIV infected patients with severe immune deficiency at the time of initiation of CART, an inflammatory reaction to asymptomatic or residual opportunistic pathogens may arise and cause serious clinical conditions or aggravation of symptoms. Typically, such reactions have been observed within the first weeks or months of initiation of CART. Relevant examples are cytomegalovirus retinitis, generalised and/or focal mycobacterial infections and Pneumocystis jiroveci pneumonia. Any inflammatory symptoms should be evaluated and treatment instituted when necessary.
Autoimmune disorders (such as Graves' disease and autoimmune hepatitis) have also been reported to occur in the setting of immune reactivation; however, the reported time to onset is more variable and these events can occur many months after initiation of treatment.
Pregnancy
Edurant should be used during pregnancy only if the potential benefit justifies the potential risk. Lower exposures of rilpivirine were observed when rilpivirine 25 mg once daily was taken during pregnancy. In the Phase III studies, lower rilpivirine exposure, similar to that seen during pregnancy, has been associated with an increased risk of virological failure, therefore viral load should be monitored closely. Alternatively, switching to another ART regimen could be considered.
Important information about some of the ingredients of EDURANT
EDURANT contains lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicinal product.
Undesirable effects
During the clinical development program (1,368 patients in the Phase III controlled trials TMC278-C209 (ECHO) and TMC278-C215 (THRIVE)), 55.7% of subjects experienced at least one adverse drug reaction. The most frequently reported adverse drug reactions (ADRs) (>= 2%) that were at least of moderate intensity were depression (4.1%), headache (3.5%), insomnia (3.5%), rash (2.3%), and abdominal pain (2.0%). The most frequent serious treatment-related ADRs were reported in 7 (1.0%) patients receiving rilpivirine. The median duration of exposure for patients in the rilpivirine arm and efavirenz arm was 104.3 and 104.1 weeks, respectively. Most ADRs occurred in the first 48 weeks of treatment.
Selected treatment emergent clinical laboratory abnormalities (grade 3 or grade 4), considered as ADRs, reported in EDURANT treated patients were increased pancreatic amylase (3.8%), increased AST (2.3%), increased ALT (1.6%), increased LDL cholesterol (fasted, 1.5%), decreased white blood cell count (1.2%), increased lipase (0.9%), increased bilirubin (0.7%), increased triglycerides (fasted, 0.6%), decreased haemoglobin (0.1%), decreased platelet count (0.1%), and increased total cholesterol (fasted, 0.1%).
Tabulated list of adverse reactions is available in the full information leaflet.
Description of selected adverse reactions
Immune reactivation syndrome
In HIV infected patients with severe immune deficiency at the time of initiation of combination antiretroviral therapy (CART), an inflammatory reaction to asymptomatic or residual opportunistic infections may arise. Autoimmune disorders (such as Graves' disease and autoimmune hepatitis) have also been reported; however, the reported time to onset is more variable and these events can occur many months after initiation of treatment.
Breast-feeding
It is not known whether rilpivirine is excreted in human milk. Rilpivirine is excreted in the milk of rats. Because of both the potential for HIV transmission and the potential for adverse reactions in breastfed infants, mothers should be instructed not to breast-feed if they are receiving rilpivirine.
About
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About GSK
GSK is a science-led global healthcare company. For further information please visit www.gsk.com/about-us.
Cautionary statement regarding forward-looking statements
GSK cautions investors that any forward-looking statements or projections made by GSK, including those made in this announcement, are subject to risks and uncertainties that may cause actual results to differ materially from those projected. Such factors include, but are not limited to, those described in the Company's Annual Report on Form 20-F for 2021, GSK's Q1 Results for 2022 and any impacts of the COVID-19 pandemic.
References
[*] Edurant and Vocabria tablets to be taken as an oral lead in before initiating injections
[1] VOCABRIA package insert. Japan Approval
[2] de los Rios P, Okoli C, Castellanos C, et al. Treatment aspirations and attitudes towards innovative medications among people living with HIV in 25 countries. Population Medicine, 2020;2(July):23.
[3] de los Rios P, Okoli C, Castellanos E, et al. Physical, Emotional and Psychosocial Challenges Associated with Daily Dosing of HIV Medications and Their Impact on Indicators of Quality of Life: Findings from the Positive Perspectives Study. AIDS and Behavior 2020.
[4] UNAIDS Country Factsheets:
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