ViiV Healthcare presents positive new findings from two studies of its investigational, long-acting regimen of cabotegravir and rilpivirine, including five-year data showing long-term durability, efficacy, safety, and tolerability

London, 22 October 2020 – ViiV Healthcare, the global specialist HIV company majority owned by GSK, with Pfizer Inc. and Shionogi Limited as shareholders, today announced positive new findings from two studies of the investigational, long-acting regimen of cabotegravir and rilpivirine for the treatment of HIV. Five-year findings from the LATTE-2 study, which is the longest study of long-acting cabotegravir and rilpivirine to date, demonstrated continued high rates of virologic response, long-term durability, and good overall tolerability whether the regimen was administered every two months or once-monthly.

Twelve-month findings from the POLAR study, which included participants who rolled over from the phase II LATTE study, demonstrated continued durable viral suppression with no incidence of virologic failure among participants who switched to long-acting injectable cabotegravir and rilpivirine administered every two months after prior long-term treatment with once-daily, oral cabotegravir and rilpivirine. These data were presented today at the 2020 Infectious Diseases Society of America (IDSA) IDWeek^TM.

Kimberly Smith, M.D., MPH, Head of Research & Development at ViiV Healthcare, said: “It’s unusual and remarkable to have five-year data for a new HIV treatment and we are so appreciative of the LATTE-2 participants who chose to stay on this regimen for such a long period of time. The data from LATTE-2 continues to establish the efficacy, tolerability and durability of this long acting regimen. The POLAR data reinforces previous findings that individuals can successfully transition from daily oral therapy directly to dosing every two months. As seen with previous studies with the long-acting regimen, participants in POLAR expressed a high rate of satisfaction and preference for the injectable regimen over a daily pill.”

LATTE-2 five-year efficacy and safety results
The phase IIb LATTE-2 study demonstrated after five years (256 weeks) that the long-acting regimen of cabotegravir and rilpivirine, administered every two months or once monthly, demonstrated high rates of virologic response, long-term durability of virologic response and good overall tolerability.

LATTE-2 included 274 participants who were first placed on an oral, three-drug regimen for 20 weeks and then randomised to receive either the long-acting injectable regimen of cabotegravir and rilpivirine once monthly, every two months, or to continue the oral, three-drug regimen. After 96 weeks, participants on the oral regimen were given the option of transitioning to the long-acting once-monthly or every-two-month regimen. After five years, 88% (101/115) of participants receiving the every-two-month regimen and 74% (85/115) of the participants receiving the once-monthly regimen remained virally suppressed. Of the participants on the oral comparator arm who elected to switch to either injectable regimen at Week 96, 93% (41/44) remained virally suppressed at five years.

A total of 44 of the 230 participants in the every-two-month and once-monthly arms weren’t virally suppressed after five years and 91% of these (40/44) had no virologic data available for review at that time point because they had left the study, which is common for a clinical trial of this duration. While two participants developed protocol-defined virologic failure (PDVF) through Week 48 on the every-two-month dosing arm, one with treatment-emergent, non-nucleoside reverse transcriptase inhibitor (NNRTI) and integrase inhibitor (INI) resistance, there have been no additional PDVF cases observed on any arm through five years.

Consistent with the established safety profile of the regimen, a majority of participants reported an injection site reaction (ISR) through five years of treatment, of which 99% were mild or moderate and resolved by three days on average. ISRs occurred less frequently over time through 96 weeks and remained consistent from that point through five years. Excluding ISRs, the most common adverse events (AEs) were nasopharyngitis (45%), diarrhoea (28%), and headache (24%). Less than three percent (3/115) of participants taking the every-two-months regimen and 17% (20/115) of participants taking the once-monthly regimen had AEs leading to withdrawal or discontinuation. Five participants withdrew for injection related events over the course of five years of treatment.

POLAR 12-month efficacy and safety results
The phase IIb POLAR study demonstrated at Month 12 that no participant lost viral suppression (HIV-1 RNA  50 c/mL) after switching to the long-acting, every-two-month regimen of cabotegravir and rilpivirine from their prior, once-daily, oral regimen of cabotegravir and rilpivirine. Through Month 12, no participants met the criteria for chronic virologic failure (confirmed plasma HIV-1 RNA >200 c/mL).

The POLAR study included 97 virologically suppressed people living with HIV that included participants who rolled over from the phase II LATTE study after completing at least six years (312 weeks) of study. At the time of rollover, participants who were on daily oral cabotegravir and rilpivirine were offered the option to switch to long-acting cabotegravir and rilpivirine administered every two months or to a daily oral regimen of dolutegravir and rilpivirine for continued maintenance of HIV suppression. In total, 90 participants (93%) chose to receive long-acting cabotegravir and rilpivirine with the other seven participants (7%) choosing to receive daily oral dolutegravir and rilpivirine. Due to the limited population size and unbalanced number of participants between arms, direct comparisons between long-acting cabotegravir and rilpivirine and daily oral dolutegravir and rilpivirine could not be drawn.

Treatment with long-acting cabotegravir and rilpivirine was generally well-tolerated, with a low rate of serious adverse events (SAEs) (5/90 [6%]), one of which was considered drug-related. Of the participants who received long-acting cabotegravir and rilpivirine, 78% (70/90) reported an ISR at some point through the 12-month study. A majority of injections did not result in ISRs being reported, as 463 ISRs (30%) were reported out of a total of 1,534 injections administered during the 12-month study. All ISR events were mild or moderate (mild: [84%] 389/463, moderate: [16%] 74/463) and lasted an average of three days. Excluding ISRs, the most common adverse events (AEs) were nasopharyngitis (11%), upper respiratory tract infections (11%), diarrhoea (10%), and pyrexia (10%). Two participants (2%) experienced AEs that led to withdrawal.

At Month 12, 88% of the participants who received long-acting cabotegravir and rilpivirine selected long-acting cabotegravir and rilpivirine as their preferred regimen compared to oral therapy. The most commonly cited reasons for the preference of long-acting cabotegravir and rilpivirine included increased convenience (69%) and the reduced frequency of administration (57%).

Anthony Mills, M.D., POLAR Principal Investigator and CEO of the Men’s Health Foundation, said: “The high levels of virologic suppression and favourable safety profile seen in the POLAR study reinforce long-acting cabotegravir and rilpivirine as a potential treatment option for people living with HIV. It was particularly exciting to see so many participants in this group make the initial choice to switch to the long-acting regimen from their prior oral therapy, and to then observe high rates of satisfaction and preference for the injectable regimen after previously having received daily oral therapy for at least five years. Taken together, these promising results indicate that long-acting cabotegravir and rilpivirine is an efficacious, well-tolerated therapy for people living with HIV that may be preferable to daily oral therapy.”

The long-acting regimen of cabotegravir and rilpivirine was approved by Health Canada in March 2020 and is currently under review by the US Food and Drug Administration and other global regulatory authorities. The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency’s (EMA) recently issued a positive opinion recommending marketing authorisation for long-acting cabotegravir and rilpivirine in both injectable and tablet formulations. The CHMP positive opinion is one of the final steps before marketing authorisation is granted by the European Commission, which has the authority to approve medicines for use throughout the European Union.

About POLAR (NCT03639311)
POLAR is a phase IIb, multicenter, rollover study in 97 antiretroviral experienced, virologically suppressed adults living with HIV designed to assess the antiviral activity and safety of long-acting cabotegravir and rilpivirine administered every two months. Participants in POLAR rolled over from the LATTE study (NCT01641809) after completing at least 312 weeks on study with plasma HIV-1 RNA <50 c/mL, while receiving a two-drug regimen consisting of once-daily oral cabotegravir 30 mg plus rilpivirine 25 mg. Participants were then offered the option to switch to the long-acting, every-two-month intramuscular injections of long-acting cabotegravir and rilpivirine or the oral fixed dose combination of dolutegravir plus rilpivirine, for the continued maintenance of HIV-1 RNA suppression, known as the Maintenance Phase (From Day 1 to Commercial Approval).

The duration of the POLAR study will vary from country to country, until the regimen of long-acting cabotegravir and rilpivirine receives regulatory approval and becomes commercially available.

For further information please see https://clinicaltrials.gov/ct2/show/NCT03639311.

About LATTE-2 (NCT02120352)
LATTE-2 is a phase IIb, multicentre, parallel-group, open-label study in ART-naïve HIV-infected adults designed to test the antiviral activity, tolerability, and safety of two intramuscular dosing regimens of a long-acting, two-drug regimen of cabotegravir and rilpivirine. After a 20-week induction period on oral cabotegravir and abacavir/lamivudine, suppressed participants were randomised 2:2:1 to receive the long-acting injectable cabotegravir and rilpivirine every eight weeks, every four weeks or to continue the oral cabotegravir and abacavir/lamivudine. After 96 weeks participants on the oral cabotegravir and abacavir/lamivudine regimen chose an injectable regimen of every eight or four weeks in the extension phase.

For further information please see https://clinicaltrials.gov/ct2/show/NCT02120352.

About the long-acting regimen of cabotegravir and rilpivirine
The long-acting regimen of cabotegravir and rilpivirine is an investigational regimen for the treatment of HIV-1 infection in adults to replace the current antiretroviral regimen in people living with HIV who are virologically stable and suppressed (HIV-1 RNA less than 50 copies/mL). 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, part of the Janssen Pharmaceutical Companies of Johnson & Johnson.

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.

CABENUVA (cabotegravir and rilpivirine extended release injectable suspensions) is currently only approved in Canada.

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/about-us.