TIDMGSK
RNS Number : 5355M
GlaxoSmithKline PLC
21 January 2021
Issued: 21 January 2021, London, UK
ViiV Healthcare announces FDA approval of Cabenuva
(cabotegravir, rilpivirine), the first and only complete
long-acting regimen for HIV treatment
Cabenuva allows virologically suppressed adults living with HIV
without prior treatment failure or resistance to cabotegravir or
rilpivirine to maintain viral suppression with 12 dosing days per
year
London, 21 January 2021 - ViiV Healthcare, the global specialist
HIV company majority owned by GlaxoSmithKline plc ("GSK"), with
Pfizer Inc. and Shionogi Limited as shareholders, today announced
that the US Food and Drug Administration (FDA) approved Cabenuva,
the first and only complete
long-acting regimen for the treatment of HIV-1 infection in
adults. Cabenuva is provided as a co-pack with two injectable
medicines - ViiV Healthcare's cabotegravir and Janssen's
rilpivirine - dosed once monthly, as an option to replace the
current antiretroviral (ARV) regimen in those who are virologically
suppressed (HIV-1 RNA less than 50 copies per milliliter [mL]) on a
stable regimen, with no history of treatment failure, and with no
known or suspected resistance to either cabotegravir or
rilpivirine. Prior to initiating treatment of Cabenuva, oral dosing
of cabotegravir and rilpivirine should be administered for
approximately one month to assess the tolerability of each
therapy.(1)
Lynn Baxter, Head of North America, ViiV Healthcare, said:
"Today's FDA approval of Cabenuva represents a shift in the way HIV
is treated, offering people living with HIV a completely new
approach to care. Cabenuva reduces the treatment dosing days from
365 days to 12 days per year. At ViiV Healthcare, we are dedicated
to ensuring no one living with HIV is left behind, and adding this
first-of-its-kind regimen to our industry-leading portfolio of
innovative medicines reinforces our mission."
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 patients from 16 countries. 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 each therapy. In these studies,
Cabenuva was as effective in maintaining viral suppression as
continuing a daily oral three-drug regimen when injected
intramuscularly in the buttocks once a month throughout the 48-week
study period. In both studies, the most common adverse reactions
(Grades 1 to 4) observed in >= 2% of clinical trial participants
receiving Cabenuva were injection site reactions, pyrexia, fatigue,
headache, musculoskeletal pain, nausea, sleep disorders, dizziness
and rash. Serious adverse events occurred in 4% (24/591) of
patients taking Cabenuva, and 3% (17/591) of adverse events led to
withdrawal.(1)
Cabenuva was preferred by nine out of 10 patients over their
previous daily oral therapy in these pivotal studies. Patient
preference data was collected from clinical trial participants who
received Cabenuva. In a pooled exploratory analysis of this
Intent-to-Treat Exposed (ITT-E) population, 532 patients completed
a single-item question at Week 48 (59 patients did not) and 88%
(523/591) preferred Cabenuva compared with two percent (9/591) who
preferred their previous ARV treatment. The results were
descriptive in nature and are not intended to imply clinical
significance.(2,3)
Dr. David Wohl, professor of medicine at the University of North
Carolina Institute of Global Health and Infectious Diseases in
Chapel Hill, said: "Among the scientific community, we recognize
the innovation behind Cabenuva is truly meaningful. Not only is it
the first, complete long-acting regimen, which allows for a
dramatic reduction in the frequency of dosing, but it also was
preferred by most clinical trial participants when compared to
their prior daily oral regimens. The FDA approval of Cabenuva
underscores the value of community-centric research and I am
pleased this new option will be available for those living with
HIV."
To support the successful delivery of the once-monthly regimen
to people living with HIV (PLHIV), ViiV Healthcare sponsored the
CUSTOMIZE trial, the first-ever, pre-approval implementation
science study to identify and evaluate approaches to integrate
Cabenuva into clinical practices in the US. Interim findings
presented at AIDS2020 demonstrated that at four months, the
majority of clinical staff participants continued to perceive the
implementation of Cabenuva as highly acceptable, feasible and
appropriate for PLHIV, and clinical staff had a substantial
decrease in what they thought would be barriers to implementation
of the injectable regimen.(4)
Brett Andrews, CEO of PRC, said: "PRC provides legal, workforce
and behavioral health services for those affected by HIV/AIDS in
San Francisco. For years, many of our clients have struggled to
manage their health while working to stabilize key aspects of their
lives. Cabenuva will provide some people living with HIV greater
freedom to pursue vocational, educational and other opportunities,
like travel, without the need for daily oral medication management.
A long-acting regimen is an innovation we have been waiting
for."
ViiV Healthcare will begin shipping Cabenuva to wholesalers and
specialty distributors in the US in February 2021.
The New Drug Application for Vocabria (cabotegravir) 30
milligram (mg) oral tablets was also approved by the FDA. Vocabria
is indicated, in combination with rilpivirine tablets, as a
complete regimen for short-term treatment of HIV-1 infection in
adults who are virologically stable and suppressed (HIV-1 RNA less
than 50 copies/mL) on a stable ARV regimen with no history of
treatment failure and with no known or suspected resistance to
either cabotegravir or rilpivirine, for use as an oral lead-in to
assess tolerability of cabotegravir prior to initiating Cabenuva
and as an oral therapy for patients who will miss planned injection
dosing of Cabenuva.
About Cabenuva (cabotegravir, rilpivirine)
Cabenuva is indicated as a complete regimen for the treatment of
HIV-1 infection in adults who are virologically suppressed (HIV-1
RNA less than 50 copies per milliliter [mL]) on a stable regimen,
with no history of treatment failure, and with no known or
suspected resistance to either cabotegravir or rilpivirine.
Cabenuva is administered as two intramuscular injections
(cabotegravir and rilpivirine) in the buttocks during the same
visit at a specialist clinic by a healthcare professional.
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, one of the Janssen
Pharmaceutical Companies of Johnson & Johnson. Rilpivirine is
approved in the US as a 25mg tablet taken once-a-day for the
treatment of HIV-1 in combination with other antiretroviral agents
in antiretroviral treatment-naïve patients 12 years of age and
older and weighing at least 35-kg with a viral load <= 100,000
HIV RNA copies/mL.
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.
About ATLAS and FLAIR
ATLAS ( NCT02951052 ) is a phase III, open-label,
active-controlled, multicenter, parallel-group, non-inferiority
study designed to assess the antiviral activity and safety of a
two-drug regimen of long-acting, injectable cabotegravir and
rilpivirine dosed every four weeks compared to continuation of
current oral ARV of two nucleoside reverse transcriptase inhibitors
(NRTIs) plus an integrase inhibitor (INI), NNRTI, or protease
inhibitor (PI) among virally suppressed individuals. The primary
endpoint for ATLAS is the proportion of participants with plasma
HIV-1 RNA >=50 c/mL per the FDA Snapshot algorithm at Week 48
(Missing, Switch, or Discontinuation = Failure, ITT-E population).
Subjects were required to be virally suppressed for six months or
greater, on first or second regimen, with no prior failure.
ATLAS includes 616 men and women living with HIV and is being
conducted at research centers in Argentina, Australia, Canada,
France, Germany, Italy, Mexico, Russia, South Africa, South Korea,
Spain, Sweden, and the United States.
FLAIR ( NCT02938520 ) is a phase III, randomized, open-label,
multicenter, parallel-group, non-inferiority study designed to
assess the antiviral activity and safety of a two-drug regimen of
intramuscular, long-acting, injectable cabotegravir and rilpivirine
in virologically suppressed adults living with HIV, following 20
weeks of induction therapy with Triumeq
(abacavir/dolutegravir/lamivudine). The primary endpoint for FLAIR
is the proportion of participants with plasma HIV-1 RNA >=50
c/mL per the FDA Snapshot algorithm at Week 48 (Missing, Switch, or
Discontinuation = Failure, ITT-E population).
FLAIR includes 566 men and women living with HIV and is being
conducted at research centers in Canada, France, Germany, Italy,
Japan, the Netherlands, Russia, South Africa, Spain, the United
Kingdom, and the United States.
Important Safety Information for Cabenuva
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 Cabenuva.
-- 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
Cabenuva. 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 Cabenuva.
Please see full Prescribing Information .
Important Safety Information for Vocabria
Vocabria is a human immunodeficiency virus type-1 (HIV-1)
integrase strand transfer inhibitor (INSTI) indicated in
combination with rilpivirine for short-term treatment of HIV-1
infection in adults who are virologically suppressed (HIV-1 RNA
less than 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, for use as:
-- oral lead-in to assess the tolerability of cabotegravir prior
to administration of Cabenuva (cabotegravir; rilpivirine)
extended-release injectable suspensions.
-- oral therapy for patients who will miss planned injection dosing with Cabenuva.
CONTRAINDICATIONS
-- Previous hypersensitivity reaction to cabotegravir.
-- Coadministration with carbamazepine, oxcarbazepine,
phenobarbital, phenytoin, rifampin, and rifapentine.
WARNINGS AND PRECAUTIONS
-- Hypersensitivity reactions have been reported in association
with other integrase inhibitors. Discontinue Vocabria immediately
if signs or symptoms of hypersensitivity reactions develop.
-- Hepatotoxicity has been reported in patients receiving
cabotegravir. Monitoring of liver chemistries is recommended.
Discontinue Vocabria if hepatotoxicity is suspected.
-- Depressive disorders have been reported with Vocabria. Prompt
evaluation is recommended for depressive symptoms.
-- Risks Associated with Combination Treatment: Review the
prescribing information for rilpivirine prior to initiation of
Vocabria in combination with rilpivirine.
ADVERSE REACTIONS
The most common adverse reactions (Grades 1 to 4) observed in at
least 3 subjects receiving Vocabria were headache, nausea, abnormal
dreams, anxiety, and insomnia.
DRUG INTERACTIONS
-- Refer to the full prescribing information for important drug interactions with Vocabria.
-- Because Vocabria in combination with rilpivirine is a
complete regimen, coadministration with other antiretroviral
medications for the treatment of HIV-1 infection is not
recommended.
-- Drugs that induce uridine diphosphate glucuronosyltransferase
(UGT)1A1 may decrease the plasma concentrations of
cabotegravir.
USE IN SPECIFIC POPULATIONS
Lactation: Breastfeeding is not recommended due to the potential
for HIV-1 transmission.
Please see full Prescribing Information.
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 ViiV Healthcare's Patient Assistance Program
ViiV Healthcare is committed to providing assistance to eligible
people living with HIV in the US who need our medicines. ViiV
Healthcare's centralized service, ViiV Connect, provides
comprehensive information on access and coverage to help patients
living in the US get their prescribed ViiV Healthcare medicines
whether they are insured, underinsured or uninsured. ViiV Connect
provides one-on-one support from dedicated access coordinators, as
well as having an integrated website, one site with many resources,
including a portal. For more information on ViiV Connect, visit
www.viivconnect.com .
About GSK
GSK is a science-led global healthcare company with a special
purpose: to help people do more, feel better, live longer.
ViiV Healthcare Media
inquiries: Audrey Abernathy +1 919 605 4521
Sofia Kalish +44 (0) 7341 079531
GSK inquiries:
Media inquiries: Simon Steel +44 (0) 20 8047 (London)
5502
Tim Foley +44 (0) 20 8047 (London)
5502
Kristen Neese +1 804 217 8147 (Philadelphia)
Kathleen Quinn +1 202 603 5003 (Washington DC)
Analyst/Investor inquiries: Sarah Elton-Farr +44 (0) 20 8047 (London)
5194
Sonya Ghobrial +44 (0) 7392 784784 (London)
James Dodwell +44 (0) 20 8047 (London)
2406
Jeff McLaughlin +1 215 751 7002 (Philadelphia)
Frannie DeFranco +1 215 751 4855 (Philadelphia)
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 2019
and as set out in GSK's "Principal risks and uncertainties" section
of the Q3 Results and any impacts of the COVID-19 pandemic .
__________________________
[1] Cabenuva (cabotegravir, rilpivirine) Prescribing
Information. US Approval January 2021.
(2) Swindells S, Andrade-Villnueva J-F, Richmond GJ, et al.
Long-Acting Cabotegravir and Rilpivirine for Maintenance of HIV-1
Suppression. New England Journal of Medicine, 382(12), 1112-1123.
https://doi.org/10.1056/nejmoa1904398
3 Orkin C, Arastéh K, Hernández-Mora MG, et al. Long-Acting
Cabotegravir and Rilpivirine after Oral Induction for HIV-1
Infection. New England Journal of Medicine, 382(12), 1124-1135.
https://doi.org/10.1056/nejmoa1909512
(4) Czarnogorksi M, Garris C, Wannamaker P, et al. Perceived
Implementation Barriers Decrease During Initial Stages of an
Implementation Science Hybrid III Study (CUSTOMIZE) of Cabotegravir
and Rilpivirine Long-Acting (CAB + RPV LA) in US Healthcare
Settings: Healthcare Team Perspective. Presented at 23(rd)
International AIDS Conference 2020.
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