UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
Form 6-K
REPORT OF FOREIGN PRIVATE ISSUER PURSUANT TO RULE 13a-16 OR
15d-16
UNDER THE SECURITIES EXCHANGE ACT OF 1934
For the
month of January 2021
Commission
File Number 001-15170
GlaxoSmithKline plc
(Translation
of registrant's name into English)
980 Great West Road, Brentford, Middlesex, TW8 9GS
(Address
of principal executive office)
Indicate
by check mark whether the registrant files or will file annual
reports under cover of Form 20-F or Form 40-F.
Form
20-F . . . .X. . . . Form 40-F . . . . . . . .
Indicate
by check mark if the registrant is submitting the Form 6-K in paper
as permitted by Regulation S-T Rule 101(b)(1): ____
Indicate
by check mark if the registrant is submitting the Form 6-K in paper
as permitted by Regulation S-T Rule 101(b)(7): ____
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
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Sofia
Kalish
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+44
(0) 7341 079531
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GSK inquiries:
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Media inquiries:
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Simon
Steel
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+44 (0) 20 8047 5502
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(London)
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Tim
Foley
|
+44 (0)
20 8047 5502
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(London)
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|
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Kristen
Neese
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+1 804
217 8147
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(Philadelphia)
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Kathleen
Quinn
|
+1 202
603 5003
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(Washington
DC)
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Analyst/Investor inquiries:
|
Sarah
Elton-Farr
|
+44 (0)
20 8047 5194
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(London)
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|
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Sonya
Ghobrial
|
+44 (0)
7392 784784
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(London)
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James
Dodwell
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+44 (0)
20 8047 2406
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(London)
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Jeff
McLaughlin
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+1 215
751 7002
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(Philadelphia)
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|
|
Frannie
DeFranco
|
+1 215
751 4855
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(Philadelphia)
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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 23rd International
AIDS Conference 2020.
SIGNATURES
Pursuant
to the requirements of the Securities Exchange Act of 1934, the
registrant has duly caused this report to be signed on its behalf
by the undersigned, thereunto duly authorised.
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GlaxoSmithKline plc
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(Registrant)
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Date: January
22, 2021
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By:/s/ VICTORIA
WHYTE
--------------------------
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Victoria Whyte
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Authorised
Signatory for and on
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behalf
of GlaxoSmithKline plc
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