ViiV Healthcare Announces First Global Regulatory Approval of CABENUVA; the First Complete, Long-acting, Regimen for the Treatment of HIV

• Simultaneous approval of VOCABRIA (cabotegravir oral tablets), for short-term treatment in conjunction with CABENUVA (cabotegravir and rilpivirine extended-release injectable suspensions), also granted by Health Canada
• CABENUVA reduces treatment dosing days from 365 to 12 per year

LONDON–(BUSINESS WIRE)–ViiV Healthcare, the global specialist HIV company majority owned by GSK, with Pfizer Inc. and Shionogi Limited as shareholders, today announced that Health Canada has approved CABENUVA, the first and only once-monthly, complete long-acting regimen for the treatment of HIV-1 infection in adults to replace the current antiretroviral (ARV) regimen in patients who are virologically stable and suppressed (HIV-1 RNA less than 50 copies per milliliter [mL]). VOCABRIA oral tablets, to be used for short time periods in conjunction with CABENUVA, have also been approved by Health Canada. These approvals are the first for CABENUVA and VOCABRIA anywhere in the world.

CABENUVA allows virologically suppressed adults living with HIV to maintain viral suppression while reducing their dosing schedule from 365 days to 12 days per year. VOCABRIA and CABENUVA should not be used in patients with known or suspected resistance to cabotegravir or rilpivirine. A kit with two injectable medicines—ViiV Healthcare’s cabotegravir and Janssen’s rilpivirine— CABENUVA was co-developed as part of a collaboration with Janssen and builds on ViiV Healthcare’s industry-leading portfolio centered on delivering innovative medicines for the HIV community.

Deborah Waterhouse, CEO, ViiV Healthcare, said: “Today’s approval marks a monumental step in the treatment of HIV and is a true testament to ViiV Healthcare’s R&D innovation. With CABENUVA, people living with HIV who are virologically suppressed now have an option to maintain that suppression with 12 treatments a year thereby positively impacting their lives.”

The approval of CABENUVA is based on the pivotal phase III ATLAS (Antiretroviral Therapy as Long-Acting Suppression) and FLAIR (First Long-Acting Injectable Regimen) studies that included more than 1,100 participants from 16 countries.^1,2 Prior to initiating treatment with CABENUVA, oral dosing of cabotegravir and rilpivirine lead-in was administered for approximately one month to assess the tolerability of cabotegravir and rilpivirine. The studies demonstrated that CABENUVA, when injected intramuscularly in the buttocks, once a month, was as effective as continuing their daily, oral, antiretroviral regimens in maintaining viral suppression throughout the 48-week study period.

In both studies, the most common adverse reactions (Grades 1 to 4) observed in ≥ 2% of participants receiving CABENUVA were injection site reactions, pyrexia, fatigue, headache, musculoskeletal pain, nausea, sleep disorders, dizziness, rash, and diarrhoea. Over the 48-week study period, a total of 4% of participants discontinued CABENUVA due to adverse events.³ The New England Journal of Medicine published the 48-week results of these studies in its March 4, 2020 issue.

CABENUVA was preferred over their previous daily oral therapy by approximately 9 out of 10 patients who switched to cabotegravir and rilpivirine long-acting in ATLAS and FLAIR studies. Treatment preference data was collected from ATLAS and FLAIR clinical trial participants who received CABENUVA. In a pooled exploratory analysis of this Intent-to-Treat Exposed (ITT-E) population, 532 participants completed a single-item question at Week 48 (59 participants did not) and 88% (523/591) preferred CABENUVA compared with 2% (9/591) who preferred their previous ARV treatment. The results were descriptive in nature and are not intended to infer clinical significance.⁴

Chloe Orkin, M.D., Consultant Physician and Clinical Professor at Queen Mary University of London and FLAIR principal investigator, said: “CABENUVA, an injectable treatment, has the potential to transform HIV care by offering monthly instead of daily treatment to suitable patients. It reduces the frequency of dosing and is as effective as daily, oral, three-drug regimens in maintaining viral suppression among adults living with HIV. Most participants in the clinical trials preferred it over their prior oral daily regimens.”

Cabotegravir and rilpivirine complete long-acting regimen for the treatment of HIV-1 infection therapy is under review by the European Medicines Agency (EMA) and regulatory authorities in Switzerland and Australia. Further regulatory authority submissions are planned in the coming months. ViiV Healthcare is working closely with the FDA to determine the appropriate next steps for a New Drug Application in the US.

About CABENUVA (cabotegravir and rilpivirine extended release injectable suspensions) and VOCABRIA (cabotegravir tablets)

CABENUVA is indicated as a complete regimen for the treatment of HIV-1 infection in adults to replace the current antiretroviral regimen in patients who are virologically stable and suppressed (HIV-1 RNA less than 50 copies/mL). CABENUVA is administered intramuscularly as two individual injections in the buttocks once a month by a healthcare provider.

VOCABRIA is indicated, in combination with EDURANT (rilpivirine tablets), as a complete regimen for short-term treatment of human immunodeficiency virus type 1 (HIV-1) infection in adults who are virologically stable and suppressed (HIV-1 RNA less than 50 copies/mL) as an oral lead-in to assess tolerability of cabotegravir prior to initiating CABENUVA and as an oral bridging therapy for missed CABENUVA injections.

VOCABRIA and CABENUVA should not be used in patients with known or suspected resistance to 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 UC. Each of these medicines are also approved as once-daily oral tablets. Once-daily oral cabotegravir and rilpivirine tablets may be used as a lead-in, to establish the tolerability of cabotegravir and rilpivirine prior to CABENUVA injection as well as for up to two months to replace monthly injectable CABENUVA therapy when injectable doses are missed.

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. Rilpivirine is an NNRTI that works by interfering with an enzyme called reverse transcriptase, which in turn stops the virus from multiplying.

Trademarks are owned by or licensed to the ViiV Healthcare group of companies. EDURANT is owned by or licensed to Janssen Sciences Ireland UC.

Important Safety Information for CABENUVA

Indications and clinical use:

CABENUVA (cabotegravir and rilpivirine extended release injectable suspensions) 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 patients who are virologically stable and suppressed (HIV-1 RNA <50 copies/mL).

VOCABRIA (cabotegravir tablets) is indicated, in combination with EDURANT (rilpivirine tablets), as a complete regimen for short-term treatment of human immunodeficiency virus type 1 (HIV-1) infection in adults who are virologically stable and suppressed (HIV-1 RNA <50 copies/mL) as: An oral lead-in to assess tolerability of cabotegravir prior to initiating CABENUVA

• Oral bridging therapy for missed CABENUVA injections

Geriatrics (>65 years of age): Not sufficiently studied to determine if they respond differently than patients <65 years of age.

Pediatrics (<18 years of age): Safety and efficacy not established

Contraindications:

In combination with:

• Anticonvulsants: Carbamazepine, oxcarbazepine, phenobarbital, and phenytoin
• Antimycobacterials: Rifabutin, rifampin, rifapentine
• Glucocorticoid: Systemic dexamethasone (more than a single dose)
• St John’s wort (Hypericum perforatum)

Relevant warnings and precautions:

• Should not be used in patients with known or suspected resistance to cabotegravir or rilpivirine
• Patients may still develop opportunistic infections and other complications of HIV infection
• Risk of transmission: precautions should be taken
• Depressive disorders
• Hepatotoxicity (serum transaminase elevations)
• Hepatic adverse events; increased risk for worsening or development of transaminase elevations in patients with hepatitis B or C co-infection or marked elevations in transaminases prior to treatment; monitoring of liver chemistries is recommended
• Loss of virologic response due to drug interactions; review concomitant medications during therapy
• Caution when used in combination with drugs that have a risk of Torsade de Pointes
• Skin and hypersensitivity reactions; discontinue immediately if signs or symptoms develop
• Administer the oral lead-in dosing prior to administration of CABENUVA to help identify patients who may be at risk of a hypersensitivity reaction
• Residual concentrations of cabotegravir and rilpivirine injections may remain in the systemic circulation of patients for up to 12 months or longer
• Risk of resistance due to treatment discontinuation
• Post-injection reactions within minutes after the injection of rilpivirine, including dyspnea, agitation, abdominal cramping, flushing, sweating, oral numbness, and changes in blood pressure. Reported in <0.5% of subjects and began to resolve minutes after the injection, and may have been associated with inadvertent (partial) IV administration
• Insufficient data in pregnant women; should not be used unless the potential benefits outweigh the potential risks
• HIV-1-infected mothers should not breastfeed their infants if receiving CABENUVA

For more information:

Please consult the Product Monograph at cabenuvapm.viivhealthcare.ca for additional important information relating to adverse reactions, drug interactions, and dosing. The Product Monograph is also available by calling 1-877-393-8448. To report an adverse event, please call 1-877-393-8448.

About ViiV Healthcare

ViiV Healthcare is a global specialist HIV company established in November 2009 by GlaxoSmithKline (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 becoming infected with HIV. Shionogi joined in October 2012. The company’s aim is to take a deeper and broader interest in HIV/AIDS than any company has done before and take a new approach to deliver effective and innovative medicines for HIV treatment and prevention, as well as support communities affected by HIV.

For more information on the company, its management, portfolio, pipeline and commitment, please visit www.viivhealthcare.com.

About GSK

GSK is a science-led global healthcare company with a special purpose: to help people do more, feel better, live longer. For further information please visit www.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 ‘Principal risks and uncertainties’ in the company’s Annual Report on Form 20-F for 2019.

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¹ Swindells S, Andrade-Villanueva J-F, Richmond G, et al. Long-acting cabotegravir and rilpivirine for maintenance of HIV-1 suppression. N Engl J Med. DOI: 10.1056/ NEJMoa1904398.

² Orkin C, Arasteh K, Hernandez-Mora MG, et al. Long-acting cabotegravir and rilpivirine after oral induction for HIV-1 infection. N Engl J Med. DOI: 10.1056/ NEJMoa1909512.

³ VOCABRIA (cabotegravir tablets) and CABENUVA (cabotegravir and rilpirivine extended release injectable suspensions) Canadian Product Monograph. March 2020.

⁴ Overton ET, Orkin C, Swindell S, et al. Monthly long-acting cabotegravir and rilpivirine is non-inferior to oral ART as maintenance therapy for HIV-1 infection: Week 48 pooled analysis from the phase 3 ATLAS and FLAIR studies. Presented at IAS 2019.

Contacts

ViiV Healthcare Media enquiries:

Audrey Abernathy, +1 919 605 4521

Patricia O’Connor, +44 20 8047 5982

GSK Global Media enquiries:

Simon Steel, +44 (0) 20 8047 5502

Kathleen Quinn, +1 202 603 5003

Analyst/Investor enquiries:

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Jeff McLaughlin, +1 215 751 7002