ViiV Healthcare, the global specialist HIV company majority owned by GlaxoSmithKline plc (?GSK?), with Pfizer Inc. and Shionogi Limited as shareholders, today presented positive long-term data from its global phase IIIb ATLAS-2M study of the first complete, long-acting regimen of cabotegravir and rilpivirine for the treatment of HIV. Week 96 findings reinforce the primary (proportion of participants with plasma HIV-1 RNA =50 c/mL at Week 48 (Snapshot, ITT-E)), and secondary endpoints (proportion of participants with plasma HIV-1 RNA =50 or <50 c/mL at Week 96 (Snapshot, ITT-E)), initially assessed at Week 48, and now showing efficacy of both monthly dosing and every 2-month dosing over the long-term in virologically supressed adults with HIV-1.? These data were presented at the virtual Conference on Retroviruses and Opportunistic Infections (CROI 2021). The every 2-month dosing regimen of cabotegravir and rilpivirine is under investigation and not approved in the US or Canada. Hans J?eger, MD, former Medical Director of MVZ Karlsplatz, HIV Research and Clinical Care Centre, Munich, and investigator for the ATLAS-2M study, said,??The ATLAS-2M 96-week data reinforces the therapeutic potential of this long-acting regimen for the treatment of HIV. It provides an option that could change the treatment experience for some people living with HIV by removing the need for daily pills for the treatment of HIV. Taking a pill every day can come as an unwelcome daily reminder of their HIV status or it may add to their fears that their HIV status might be disclosed by someone seeing their HIV medication. This regimen can enable people living with HIV to reduce the days they receive treatment from 365 to 12 or 6 per year, representing a paradigm shift in their experience of HIV treatment.? Kimberly Smith, M.D., Head of Research & Development at ViiV Healthcare,?said,??At ViiV Healthcare, our research and development is underpinned by a commitment to innovation and a desire to make a difference to the lives of people living with HIV. Long-acting cabotegravir and rilpivirine is a first-of-its-kind regimen that removes the need for daily therapies after the initiation phase. These long-term data confirm that every 2-month dosing is non-inferior to monthly dosing, which means people living with HIV who are virologically supressed can reduce the number of days they take treatment to 6 times per year, allowing more time between doses with this regimen.? ATLAS-2M met its primary endpoint at Week 48, demonstrating that the efficacy of long-acting cabotegravir and rilpivirine dosed every 2-months (every eight weeks) was non-inferior to monthly dosing (every four weeks). Week 48 primary endpoint (proportion of participants with plasma HIV-1 RNA =50 c/mL) results ?showed every 2-month dosing (9/522 [1.7%]) and monthly dosing (5/523 [1.0%]) were similarly effective (adjusted difference: 0.8%, 95% confidence interval [CI]: -0.6, 2.2)[2].??Week 96 findings reinforced the primary endpoint: the efficacy of every 2-month dosing was non-inferior to monthly dosing of long-acting cabotegravir and rilpivirine, with 2.1% (11/522) and 1.1% (6/523) of participants, respectively, having HIV-1 RNA =50 c/mL (adjusted difference: 1.0%, 95% CI: -0.6-2.5)[1].?The 96-week ATLAS-2M study secondary endpoint, showed that rates of virologic suppression were similar between the two arms, with 91.0% (475/522) of participants in the every 2-month dosing arm and 90.2% (472/523) in the monthly dosing arm achieving HIV-1 RNA <50 c/mL (adjusted difference: 0.8%, 95% CI: -2.8-4.3)[1]. Week 96 findings reported confirmed virologic failures (CVFs), defined as two consecutive viral loads =200 c/mL, in 1.7% (9/522) of participants in the every 2-month dosing arm and 0.4% (2/523) in the monthly dosing arm[1].?The rate of CVF was low overall [1% ( 11/1,045], with only one participant in the every 2-month dosing arm meeting the criterion in the second year of therapy. This patient developed a rilpivirine resistance-associated mutation (RAM) Y181C, and no integrase inhibitor (INSTI) RAMS[1]. Safety profiles were comparable between the two treatment arms, with no new safety signals identified since the 48-week analysis[1],[2]. Injection site reactions (ISRs) were the most common adverse events (AE) (16% [74/473] in the every 2-month dosing arm and 12% [54/468] in the monthly dosing arm), with one leading to withdrawal between weeks 48 and 96[1].?Most ISRs (99%) were mild or moderate and self-resolving, with a median duration of three days. Over the entire 96 weeks, in the every 2-month dosing arm, 1% (7/522) of participants discontinued due to ISRs, vs 2% (11/523) in the monthly dosing arm[1]. The most common non-injection site reactions drug-related AEs were pyrexia and fatigue. Grade = 3 adverse events were seen in 11% (57/522) of participants in the every 2-month arm and 12% (65/523) in the once monthly arm. Adverse events leading to withdrawal were seen in 3% (18/522) of participants in the every 2-month arm and 4% (19/523) in the monthly arm[1]. ViiV Healthcare?s cabotegravir in combination with Janssen?s rilpivirine was co-developed as part of a collaboration with Janssen and builds on ViiV Healthcare?s industry-leading portfolio that is centered on delivering innovative medicines for the HIV community.? The long-acting regimen of cabotegravir and rilpivirine is licensed as a once-monthly treatment in Canada and USA under the brand name Cabenuva.[3]?A supplemental New Drug Application has been submitted to the US Food and Drug Administration for expanding the use of Cabenuva as an HIV treatment to include use of every 2-month dosing in the US. Cabenuva is listed in Australia for both monthly and every 2-month dosing. The long-acting regimen has also received Marketing Authorisation under the brand names Vocabria (cabotegravir) and Rekambys (rilpivirine) in Europe for both monthly dosing and every 2-month dosing. Further regulatory applications have been submitted and are being reviewed by other regulatory bodies worldwide. -END- Notes to editor About cabotegravir Cabotegravir is an integrase strand transfer inhibitor (INSTI) developed by ViiV Healthcare for the treatment of HIV-1 in virologically suppressed adults. It is being evaluated in combination with injectable rilpivirine as a long-acting formulation. 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 infection. About rilpivirine The oral formulation of rilpivirine is also authorised for the treatment of HIV-1 infection in combination with other antiretroviral agents in antiretroviral treatment-na?ve patients 12 years of age and older and weighing at least 35 kg with a viral load = 100,000 HIV RNA copies/mL. Rilpivirine long-acting is a prolonged-release suspension for IM injection being developed by Janssen Sciences Ireland UC, one of the Janssen Pharmaceutical Companies of Johnson & Johnson. Rilpivirine is a non-nucleoside reverse transciptase inhibitor (NNRTI) that works by interfering with an enzyme called reverse transcriptase, which in turn stops the virus from multiplying. Administration and dosing of cabotegravir and rilpivirine Cabotegravir injection used in combination with rilpivirine injection will be the first complete long-acting regimen dosed monthly or every 2-months, for virologically suppressed people living with HIV-1. Cabotegravir and rilpivirine injections are administered as two gluteal intramuscular (IM) injections 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. Important Safety Information for Cabenuva (cabotegravir 200mg/mL; rilpivirine 300 mg/mL) extended-release injectable suspensions Cabenuva is indicated as a complete regimen for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in adults to replace the current antiretroviral regimen in those who are virologically suppressed (HIV-1 RNA less than 50 copies per mL) on a stable antiretroviral regimen with no history of treatment failure and with no known or suspected resistance to either cabotegravir or rilpivirine. CONTRAINDICATIONS

• Do not use Cabenuva in patients with previous hypersensitivity reaction to cabotegravir or rilpivirine.
• Do not use Cabenuva in patients receiving carbamazepine, oxcarbazepine, phenobarbital, phenytoin, rifabutin, rifampin, rifapentine, systemic dexamethasone (>1 dose), and St John?s wort.

WARNINGS AND PRECAUTIONS Hypersensitivity Reactions:

• Hypersensitivity reactions, including cases of Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), have been reported during postmarketing experience with rilpivirine-containing regimens. While some skin reactions were accompanied by constitutional symptoms such as fever, other skin reactions were associated with organ dysfunctions, including elevations in hepatic serum biochemistries.
• Serious or severe hypersensitivity reactions have been reported in association with other integrase inhibitors and could occur with
• Discontinue Cabenuva immediately if signs or symptoms of hypersensitivity reactions develop. Clinical status, including liver transaminases, should be monitored and appropriate therapy initiated. Prescribe the oral lead-in prior to administration of Cabenuva 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, agitation, abdominal cramping, flushing, sweating, oral numbness, and changes in blood pressure. These events may have been associated with inadvertent (partial) intravenous administration and began to resolve within a few minutes after the injection.
• Carefully follow the Instructions for Use when preparing and administering Cabenuva to avoid accidental intravenous administration. Observe patients briefly (approximately 10 minutes) after the injection. If a post-injection reaction occurs, monitor and treat as clinically indicated.

Hepatotoxicity:

• Hepatotoxicity has been reported in patients receiving cabotegravir or rilpivirine with or without known pre-existing hepatic disease or identifiable risk factors.
• Patients with underlying liver disease or marked elevations in transaminases prior to treatment may be at increased risk for worsening or development of transaminase elevations.
• Monitoring of liver chemistries is recommended and treatment with Cabenuva should be discontinued if hepatotoxicity is suspected.

Depressive Disorders:

• Depressive disorders (including depressed mood, depression, major depression, mood altered, mood swings, dysphoria, negative thoughts, suicidal ideation or attempt) have been reported with Cabenuva or the individual products.
• Promptly evaluate patients with depressive symptoms.

Risk of Adverse Reactions or Loss of Virologic Response Due to Drug Interactions:

• The concomitant use of Cabenuva and other drugs may result in known or potentially significant drug interactions (see Contraindications and Drug Interactions).
• Rilpivirine doses 3 and 12 times higher than the recommended oral dosage can prolong the QTc interval. Cabenuva should be used with caution in combination with drugs with a known risk of Torsade de Pointes.

Long-Acting Properties and Potential Associated Risks with Cabenuva:

• Residual concentrations of cabotegravir and rilpivirine may remain in the systemic circulation of patients for prolonged periods (up to 12 months or longer). Select appropriate patients who agree to the required monthly injection dosing schedule because non-adherence to monthly injections or missed doses 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. If virologic failure is suspected, switch the patient to an alternative regimen as soon as possible.

ADVERSE REACTIONS The most common adverse reactions (incidence =2%, all grades) with Cabenuva were injection site reactions, pyrexia, fatigue, headache, musculoskeletal pain, nausea, sleep disorders, dizziness, and rash. DRUG INTERACTIONS

• Refer to the applicable full Prescribing Information for important drug interactions with Cabenuva, Vocabria, or 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 1A9 are expected to decrease the plasma concentrations of cabotegravir. Drugs that induce or inhibit CYP3A may affect the plasma concentrations of rilpivirine.
• Cabenuva should be used with caution in combination with drugs with a known risk of Torsade de Pointes.

USE IN SPECIFIC POPULATIONS

• Pregnancy:?There are insufficient human data on the use of Cabenuva during pregnancy to adequately assess a drug-associated risk for birth defects and miscarriage. Discuss the benefit-risk of using Cabenuva during pregnancy and conception and consider that cabotegravir and rilpivirine are detected in systemic circulation for up to 12 months or longer after discontinuing injections of An Antiretroviral Pregnancy Registry has been established.
• Lactation:?The CDC recommends that HIV-1-infected mothers in the United States not breastfeed their infants to avoid risking postnatal transmission of HIV-1 infection. Breastfeeding is also not recommended due to the potential for developing viral resistance in HIV-positive infants, adverse reactions in a breastfed infant, and detectable cabotegravir and rilpivirine concentrations in systemic circulation for up to 12 months or longer after discontinuing injections of

Please see full?Prescribing Information. European Important Safety Information (ISI) Vocabria ISI 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 <50?copies/mL) on a stable antiretroviral regimen without present or past evidence of viral resistance to, and no prior virological failure with agents of the NNRTI and INI class Vocabria injection is indicated for the treatment of HIV-1 in combination with rilpivirine injection, therefore, the prescribing information for rilpivirine injection should be consulted for recommended dosing. Vocabria tablets are indicated in combination with rilpivirine tablets for the short-term treatment of Human Immunodeficiency Virus type 1 (HIV-1) infection in adults who are virologically suppressed (HIV-1 RNA <50 copies/mL) on a stable antiretroviral regimen without present or past evidence of viral resistance to, and no prior virological failure with agents of the NNRTI and INI class for:

• oral lead in to assess tolerability of Vocabria and rilpivirine prior to administration of long acting Vocabria injection plus long acting rilpivirine injection.
• oral therapy for adults who will miss planned dosing with Vocabria injection plus rilpivirine injection.

Vocabria tablets are only indicated for treatment of HIV-1 in combination with rilpivirine tablets, therefore, the prescribing information for Edurant tablets should also be consulted for recommended dosing. Prior to starting Vocabria injection, healthcare professionals should have carefully selected patients who agree to the required injection schedule and counsel patients about the importance of adherence to scheduled dosing visits to help maintain viral suppression and reduce the risk of viral rebound and potential development of resistance with missed doses. Following discontinuation of Vocabria and rilpivirine injection, it is essential to adopt an alternative, fully suppressive antiretroviral regimen no later than one month after the final injection of Vocabria when dosed monthly and no later than two months after the final injection of Vocabria when dosed every 2 months. Elderly (=65 years of age): No dose adjustment is required in elderly patients. There are limited data available on the use of cabotegravir in patients aged 65 years and over. Paediatrics (<18 years of age): The safety and efficacy of Vocabria in children and adolescents aged under 18 years have not been established. No data are available. Contraindications Hypersensitivity to cabotegravir or rilpivirine or to any of the excipients. Concomitant use with: rifampicin, rifapentine, carbamazepine, oxcarbazepine, phenytoin or phenobarbital. Special Warnings and Precautions for Use Vocabria injection Residual concentrations of cabotegravir may remain in the systemic circulation of patients for prolonged periods (up to 12 months or longer), therefore, physicians should take the prolonged release characteristics of Vocabria injection into consideration when the medicinal product is discontinued. If virologic failure is suspected, an alternative regimen should be adopted as soon as possible. Baseline factors associated with virological failure Before starting the regimen, it should be taken into account that multivariable analyses indicate that a combination of at least 2 of the following baseline factors may be associated with an increased risk of virological failure: archived rilpivirine resistance mutations, HIV-1 subtype A6/A1, or BMI =30 kg/m². In patients with an incomplete or uncertain treatment history without pre-treatment resistance analyses, caution is warranted in the presence of either BMI =30 kg/m²?or HIV-1 A6/A1 subtype. Hypersensitivity reactions Hypersensitivity reactions have been reported in association with other integrase inhibitors. These reactions were characterised by rash, constitutional findings and sometimes organ dysfunction, including liver injury. While no such reactions have been observed to date in association with Vocabria, physicians should remain vigilant and should discontinue Vocabria and other suspected medicinal products immediately, should signs or symptoms of hypersensitivity develop (including, but not limited to, severe rash, or rash accompanied by fever, general malaise, fatigue, muscle or joint aches, blisters, oral lesions, conjunctivitis, facial oedema, hepatitis, eosinophilia or angioedema). Clinical status, including liver aminotransferases should be monitored and appropriate therapy initiated. Administration of oral lead-in is recommended to help identify patients who may be at risk of a hypersensitivity reaction. ? Hepatoxicity Hepatotoxicity has been reported in a limited number of patients receiving Vocabria with or without known pre-existing hepatic disease. Monitoring of liver chemistries is recommended and treatment with Vocabria should be discontinued if hepatotoxicity is suspected. HBV/HCV co-infection Patients with hepatitis B co-infection were excluded from studies with Vocabria. It is not recommended to initiate Vocabria in patients with hepatitis B co-infection. Physicians should refer to current treatment guidelines for the management of HIV infection in patients co-infected with hepatitis B virus. Limited data is available in patients with hepatitis C co-infection.? Monitoring of liver function is recommended in patients with hepatitis C co-infection. Interactions with medicinal products Caution should be given to prescribing Vocabria injection and tablets with medicinal products that may reduce its exposure. Concomitant use of Vocabria injection with rifabutin is not recommended. Polyvalent cation containing antacids are recommended to be taken at least 2 hours before and 4 hours after taking Vocabria tablets. Effect of other medicinal products on the pharmacokinetics of cabotegravir Cabotegravir is primarily metabolised by uridine diphosphate glucuronosyl transferase (UGT) 1A1 and to a lesser extent by UGT1A9. Medicinal products which are strong inducers of UGT1A1 or UGT1A9 are expected to decrease cabotegravir plasma concentrations leading to lack of efficacy. Undesirable effects Summary of the safety profile The most frequently reported adverse reactions (ARs) from monthly dosing studies were injection site reactions (up to 84%), headache (up to 12%) and pyrexia^*?(10%). The most frequently reported ARs from ATLAS-2M every 2-month dosing were injection site reactions (76%), headache (7%) and pyrexia^*?(7%). ^*Pyrexia includes the following: feeling hot, body temperature increased. Description of selected adverse reactions Local injection site reactions (ISRs) Up to 1% of subjects discontinued treatment with Vocabria plus rilpivirine because of ISRs. When dosing monthly, up to 84% of subjects reported injection site reactions; out of 30393 injections, 6815 ISRs were reported. When dosing every 2 months, 76% of patients reported injection site reactions; out of 8470 injections, 2507 ISRs were reported. The severity of reactions was generally mild (Grade 1, 70%-75% of subjects) or moderate (Grade 2, 27%-36% of subjects). 3-4% of subjects experienced severe (Grade 3) ISRs. The?median duration of overall ISR events was 3 days. The percentage of subjects reporting ISRs decreased over time. Weight increased At the Week 48 time point, subjects in studies FLAIR and ATLAS, who received Vocabria plus rilpivirine gained a median of 1.5 kg in weight subjects continuing on their current antiretroviral therapy (CAR) gained a median of 1.0 kg (pooled analysis). In the individual studies FLAIR and ATLAS, the median weight gains in the Vocabria plus rilpivirine arms were 1.3 kg and 1.8 kg respectively, compared to 1.5 kg and 0.3 kg in the CAR arms. At the 48 week timepoint, in ATLAS-2M the median weight gain in both the monthly and 2-monthly CAB+RPV dosing arms was 1.0 kg. Pregnancy There are a limited amount of data from the use of cabotegravir in pregnant women. The effect of Vocabria on human pregnancy is unknown. Cabotegravir was not teratogenic when studied in pregnant rats and rabbits but, exposures higher than the therapeutic dose showed reproductive toxicity in animals. The relevance to human pregnancy is unknown. Vocabria injection is not recommended during pregnancy unless the expected benefit justifies the potential risk to the foetus. Cabotegravir has been detected in systemic circulation for up to 12 months or longer after an injection Breast-feeding It is expected that cabotegravir will be secreted into human milk based on animal data, although this has not been confirmed in humans. Cabotegravir may be present in human milk for up to 12 months or longer after the last cabotegravir injection. It is recommended that HIV infected women do not breast-feed their infants under any circumstances in order to avoid transmission of HIV. Rekambys (rilpivirine injection) ISI The following Important Safety Information is based on the Summary of Product Characteristics for Rekambys (rilpivirine injection).?Please consult the full Summary of Product Characteristics for all the safety information. Rekambys is indicated, in combination with cabotegravir injection, for the treatment of human immunodeficiency virus type?1 (HIV-1) infection in adults who are virologically suppressed (HIV-1 RNA <?50?copies/mL) on a stable antiretroviral regimen without present or past evidence of viral resistance to, and no prior virological failure with, agents of the NNRTI and INI class Rekambys should always be co-administered with a cabotegravir injection. The prescribing information for cabotegravir injection should be consulted for recommended dosing. Prior to the initiation of Rekambys, rilpivirine oral tablets, together with cabotegravir oral tablets, should be taken for approximately 1?month (at least 28?days) to assess tolerability to rilpivirine and cabotegravir. One rilpivirine 25-mg tablet should be taken with a meal with one cabotegravir 30-mg tablet once daily. Prior to starting Rekambys, the healthcare professional should carefully select patients who agree to the required injection schedule and counsel patients about the importance of adherence to scheduled dosing visits to help maintain viral suppression and reduce the risk of viral rebound and potential development of resistance associated with missed doses. Following discontinuation of Rekambys in combination with cabotegravir injection, it is essential to adopt an alternative, fully suppressive antiretroviral regimen no later than one month after the last every 1?month injection of Rekambys or two months after the last every 2?months injection of Rekambys. Elderly:?There is limited information regarding the use of Rekambys in patients >?65?years of age. No dose adjustment of Rekambys is required in older patients. Paediatric Patients:?The safety and efficacy of Rekambys in children and adolescents aged <?18?years have not been established. No data are available. Contraindications Hypersensitivity to the active substance or to any of the excipients. Rekambys must not be co-administered with the following medicinal products, which may result in loss of therapeutic effect of Rekambys:

• the anticonvulsants carbamazepine, oxcarbazepine, phenobarbital, phenytoin
• the antimycobacterials rifabutin, rifampicin, rifapentine
• the systemic glucocorticoid dexamethasone, except as a single dose treatment
• St?John?s?wort (Hypericum perforatum).

Special Warnings and Precautions for Use Risk of resistance following treatment discontinuation Long-acting properties of rilpivirine injection Residual concentrations of rilpivirine may remain in the systemic circulation of patients for prolonged periods (up to 4?years in some patients) and should be considered upon discontinuation of Rekambys. Baseline factors associated with virological failure Before starting the regimen, it should be taken into account that multivariable analyses indicate that a combination of at least 2 of the following baseline factors may be associated with an increased risk of virological failure: archived rilpivirine resistance mutations, HIV-1 subtype A6/A1, or BMI =30?kg/m². In patients with an incomplete or uncertain treatment history without pre-treatment resistance analyses, caution is warranted in the presence of BMI =30 kg/m²?and/or HIV-1 subtype A6/A1. Post-injection reactions Partial intravenous administration may result in AEs due to temporarily high plasma concentrations. In clinical studies, serious post-injection reactions were reported within minutes after the injection of rilpivirine, including dyspnoea, agitation, abdominal cramping, flushing, sweating, oral numbness, and changes in blood pressure. These events were very rare and began to resolve within a few minutes after the injection. Carefully follow the Instructions for Use when preparing and administering Rekambys to avoid accidental intravenous administration. Observe patients briefly (approximately 10?minutes) after the injection. If a patient experiences a post-injection r