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 December 2020
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): ____
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Issued: 21 December 2020, London, UK
ViiV Healthcare announces the Marketing Authorisation of the first
complete long-acting injectable HIV treatment in
Europe
●
Marketing Authorisation granted by European Commission for ViiV
Healthcare's Vocabria (cabotegravir injection and tablets) to be
used with Janssen's Rekambys (rilpivirine injection) and Edurant
(rilpivirine tablets)
●
New treatment can enable people living with HIV to reduce the days
they receive treatment from 365 to 12 or 6 per
year
●
The long-acting injectable regimen was preferred by majority of
clinical trial patients who tried the treatment over their previous
daily oral therapy
London, 21 December 2020 - ViiV Healthcare, the global specialist HIV
company majority owned by GlaxoSmithKline plc ("GSK"), with Pfizer
Inc. and Shionogi Limited as shareholders, announced the
authorisation of Vocabria (cabotegravir injection and tablets) in
combination with Janssen Pharmaceutical Companies of Johnson &
Johnson's Rekambys (rilpivirine injection) and Edurant (rilpivirine
tablets), in the European Union, for the treatment of HIV-1
infection in adults who are virologically
suppressed.[1] 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.
This authorisation represents the first time people living
with HIV in Europe may be able to receive a long-acting injectable
treatment that removes the need to take daily oral tablets,
following the oral initiation phase.
Dr Antonio Antela, University Hospital, Santiago de Compostela,
Spain, said: "Daily
antiretrovirals have transformed the lives of people living
with HIV. However, taking daily medication can pose challenges for
some people; it may act as a constant reminder of HIV or be a cause
of fear that their HIV status will be disclosed. Following the oral
initiation phase to assess the tolerability of the medicines,
cabotegravir and rilpivirine injections could reduce the number of
days of treatment per year from 365 down to 12 for the once-monthly
or 6 for the once every 2-months dosing regimen, representing a
paradigm shift in how we are able to treat and manage the
condition. The long-acting regimen of cabotegravir and rilpivirine
was as effective as treatment with current daily antiviral
therapy in the clinical trials in maintaining viral suppression, is
generally well tolerated, and could change the treatment experience
for some people living with HIV that may have challenges with daily
HIV therapies."
Outlining the need for a less frequent dosing regimen, the largest
global HIV patient-reported outcomes study to date conducted by
ViiV Healthcare, Positive Perspectives Wave 2, found that when
participants were asked about their treatment aspirations and
attitudes towards innovative medications, 55% (n=1306/2389) would
prefer not having to take medication every day, as long as their
HIV stays suppressed.[2] In
addition, 58% (n=1394/2389) noted that taking daily HIV medication
acts as a constant reminder of HIV in their lives, while up to 38%
(n=906/2389) of participants reported anxiety around the fact that
taking daily treatment could increase the chances of revealing
their HIV status to others.[3]
Deborah Waterhouse, CEO, ViiV Healthcare, said: "At ViiV Healthcare, we push the boundaries to
provide new treatment options that will help make a difference to
people's lives. We saw from the patient reported outcomes in our
pivotal clinical trials that approximately 9 out of 10 people who
switched to the long-acting regimen preferred this over their
previous daily oral tablets.4,5,6 It
will potentially change the treatment experience for some people
living with HIV by removing the need for daily HIV tablets. We are
committed to pursuing innovative research to meet the diverse needs
of the HIV community, and we won't stop until we have more ways to
treat, and hopefully one day cure, HIV."
Marketing Authorisation is based on the pivotal phase III ATLAS
(Antiretroviral Therapy as Long-Acting Suppression), FLAIR (First
Long-Acting Injectable Regimen) and ATLAS-2M studies, which
included more than 1,200 participants from 16
countries.[4],[5],[6] Cabotegravir
and rilpivirine are co-administered as two intramuscular (IM)
injections in the buttocks by a Healthcare Professional at the same
appointment.
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.
This announcement marks the second marketing authorisation of the
long-acting regimen of cabotegravir and rilpivirine with
once-monthly dosing licensed by Health Canada under the brand name
Cabenuva for the treatment of HIV-1 infection in adults who
are virologically stable and suppressed. In July, ViiV
Healthcare resubmitted the New Drug Application (NDA) for
once-monthly dosing of cabotegravir and rilpivirine to the US Food
and Drug Administration (FDA), and further regulatory applications
have been submitted and are being reviewed by other regulatory
bodies worldwide.
-END-
Notes to editor
About cabotegravir
Cabotegravir is an INI 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, 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.
About rilpivirine and rilpivirine long-acting
The oral formulation of rilpivirine is also authorised for the
treatment of HIV-1 infection 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.
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 an 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
once-monthly or once every 2-months, for virologically suppressed
people living with HIV-1. Cabotegravir and rilpivirine
injections are administered as two intramuscular (IM)
injections in the buttocks 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 (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
|
To
minimise the risk of developing viral resistance 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.
|
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 reaction, monitor and treat as clinically
indicated.
Cardiovascular
REKAMBYS should be used with caution when co-administered with a
medicinal product with a known risk of Torsade de Pointes. At
supra-therapeutic doses (75 and 300 mg once daily), oral
rilpivirine has been associated with prolongation of the QTc
interval of the electrocardiogram (ECG). Oral rilpivirine at the
recommended dose of 25 mg once daily is not associated with a
clinically relevant effect on QTc. Plasma rilpivirine
concentrations after REKAMBYS injections are comparable to those
during such oral rilpivirine therapy.
HBV/HCV co-infection
Patients with hepatitis B co-infection were excluded from studies
with REKAMBYS. It is not recommended to initiate REKAMBYS in
patients with hepatitis B co-infection. In patients co-infected
with hepatitis B receiving oral rilpivirine, the incidence of
hepatic enzyme elevation was higher than in patients receiving oral
rilpivirine who were not hepatitis B co-infected. 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. In patients co-infected with hepatitis C receiving
oral rilpivirine, the incidence of hepatic enzyme elevation was
higher than in patients receiving oral rilpivirine who were not
hepatitis C co-infected. The pharmacokinetic exposure of oral and
injectable rilpivirine in co-infected patients was comparable to
that in patients without hepatitis C co-infection. Monitoring of
liver function is recommended in patients with hepatitis C
co-infection.
Interactions with other medicinal products
REKAMBYS should not be administered with other antiretroviral
medicinal products, except for cabotegravir injection for the
treatment of HIV-1 infection.
Pregnancy
There are limited data of REKAMBYS in pregnant women. REKAMBYS is
not recommended during pregnancy unless the expected benefit
justifies the potential risk. Lower exposures of oral rilpivirine
were observed when rilpivirine 25 mg once daily was taken during
pregnancy. In the Phase 3 studies with oral rilpivirine, lower
rilpivirine exposure, similar to that seen during pregnancy, has
been associated with an increased risk of virological failure,
therefore viral load should be monitored closely. Alternatively,
switching to another ART regimen could be considered.
Undesirable effects
The most frequently reported ARs from every 1 month dosing
studies were injection site reactions (up to 84%), headache (up to
12%) and pyrexia (10%).
The most frequently reported ARs from every 2 months dosing
were injection site reactions (76%), headache (7%) and pyrexia
(7%).
Tabulated list of adverse reactions is available in the full
information leaflet.
Description of selected adverse reactions
Local Injection Site Reactions (ISRs)
Up to 1% of subjects discontinued treatment with rilpivirine and
cabotegravir injections because of ISRs. When dosing every
1 month in ATLAS, FLAIR, and ATLAS-2M (Q4W arm), up to 84% of
subjects reported injections site reactions; out of
30393 injections, 6815 ISRs were reported. When dosing
every 2 months in ATLAS-2M (Q8W arm), 76% of subjects reported
injection site reactions; out of 8470 injections,
2507 ISRs were reported.
Injection site reactions were 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 ISR events was 3 days. The percentage of subjects
reporting ISRs decreased over time.
Weight increased
At the Week 48 time point, subjects in Phase 3 Studies
FLAIR and ATLAS, who received rilpivirine plus cabotegravir gained
a median of 1.5 kg in weight; subjects continuing on their
current antiretroviral regimen (CAR) group gained a median of
1.0 kg (pooled analysis). In the individual studies FLAIR and
ATLAS, the median weight gains in the rilpivirine plus cabotegravir
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 every 2 months rilpivirine +
cabotegravir dosing arms was 1.0 kg.
Pregnancy
The effect of REKAMBYS on human pregnancy is unknown. A moderate
amount of data with oral rilpivirine in pregnant women (between
300-1000 pregnancy outcomes) indicate no malformative or
foetal/neonatal toxicity of rilpivirine. A study of 19 pregnant
women treated with oral rilpivirine in combination with a
background regimen during the second and third trimesters, and
postpartum, showed lower exposures of oral rilpivirine during
pregnancy, therefore viral load should be monitored closely if
REKAMBYS is used during pregnancy.
Animal studies do not indicate reproductive toxicity. REKAMBYS is
not recommended during pregnancy unless the expected benefit
justifies the potential risk.
An alternative oral regimen should be considered in line with
current treatment guidelines. After discontinuation of REKAMBYS,
rilpivirine may remain in systemic circulation for up to 4 years in
some patients.
Breast-feeding
It is expected that rilpivirine will be secreted into human milk
based on animal data, although this has not been confirmed in
humans. Rilpivirine may be present in human milk for up to 4 years
in some patients after discontinuation of REKAMBYS.
It is recommended that HIV infected women do not breast-feed their
infants under any circumstances in order to avoid transmission of
HIV.
Edurant (rilpivirine tablet) ISI
Please refer to the full Summary of Product Characteristics for
full prescribing information for EDURANT®
(rilpivirine): https://www.medicines.org.uk/emc/product/4968/smpc
Important Safety Information (ISI)
The following Important Safety Information is based on the Summary
of Product Characteristics for EDURANT® Please consult
the full Summary of Product Characteristics for all the safety
information.
EDURANT, in combination with other antiretroviral medicinal
products, is indicated for the treatment of human immunodeficiency
virus type 1 (HIV-1) infection in antiretroviral
treatment-naïve patients 12 years of age and older with a
viral load ≤ 100,000 HIV-1 RNA copies/ml.
Genotypic resistance testing should guide the use of
EDURANT.
The recommended dose of EDURANT is one 25 mg tablet taken once
daily. EDURANT must be taken with a meal.
Elderly: There is limited
information regarding the use of EDURANT in patients
> 65 years of age. No dose adjustment of EDURANT
is required in older patients. EDURANT should be used with caution
in this population.
Paediatric population: The
safety and efficacy of EDURANT in children aged
< 12 years have not yet been established. No data are
available.
Contraindications
Hypersensitivity to the active substance or to any of the
excipients.
EDURANT should not be co-administered with the following medicinal
products, as significant decreases in rilpivirine plasma
concentrations may occur (due to CYP3A enzyme induction or gastric
pH increase), which may result in loss of therapeutic effect of
EDURANT:
●
the
anticonvulsants carbamazepine, oxcarbazepine, phenobarbital,
phenytoin
●
the
antimycobacterials rifampicin, rifapentine
●
proton
pump inhibitors, such as omeprazole, esomeprazole, lansoprazole,
pantoprazole, rabeprazole
●
the
systemic glucocorticoid dexamethasone, except as a single dose
treatment
●
St John's wort (Hypericum
perforatum).
Special Warnings and Precautions for Use
While effective viral suppression with antiretroviral therapy has
been proven to substantially reduce the risk of sexual
transmission, a residual risk cannot be excluded. Precautions to
prevent transmission should be taken in accordance with national
guidelines.
Virologic failure and development of resistance
EDURANT has not been evaluated in patients with previous virologic
failure to any other antiretroviral therapy.
In the pooled efficacy analysis from the Phase III trials in
adults through 96 weeks, patients treated with rilpivirine
with a baseline viral load
> 100,000 HIV-1 RNA copies/ml had a greater
risk of virologic failure (18.2% with rilpivirine versus 7.9% with
efavirenz) compared to patients with a baseline viral load
≤ 100,000 HIV-1 RNA copies/ml (5.7% with
rilpivirine versus 3.6% with efavirenz). The greater risk of
virologic failure for patients in the rilpivirine arm was observed
in the first 48 weeks of these trials. Patients with a
baseline viral load
> 100,000 HIV-1 RNA copies/ml who
experienced virologic failure exhibited a higher rate of
treatment-emergent resistance to the non-nucleoside reverse
transcriptase inhibitor (NNRTI) class. More patients who failed
virologically on rilpivirine than who failed virologically on
efavirenz developed lamivudine/emtricitabine associated
resistance.
As with other antiretroviral medicinal products, resistance testing
should guide the use of rilpivirine.
Cardiovascular
At supra-therapeutic doses (75 and 300 mg once daily),
rilpivirine has been associated with prolongation of the QTc
interval of the electrocardiogram (ECG). EDURANT at the recommended
dose of 25 mg once daily is not associated with a clinically
relevant effect on QTc. EDURANT should be used with caution when
co-administered with medicinal products with a known risk of
Torsade de Pointes.
Immune reactivation syndrome
In HIV infected patients with severe immune deficiency at the time
of initiation of CART, an inflammatory reaction to asymptomatic or
residual opportunistic pathogens may arise and cause serious
clinical conditions or aggravation of symptoms. Typically, such
reactions have been observed within the first weeks or months of
initiation of CART. Relevant examples are cytomegalovirus
retinitis, generalised and/or focal mycobacterial infections
and Pneumocystis jiroveci pneumonia.
Any inflammatory symptoms should be evaluated and treatment
instituted when necessary.
Autoimmune disorders (such as Graves' disease and autoimmune
hepatitis) have also been reported to occur in the setting of
immune reactivation; however, the reported time to onset is more
variable and these events can occur many months after initiation of
treatment.
Pregnancy
Edurant should be used during pregnancy only if the potential
benefit justifies the potential risk. Lower exposures of
rilpivirine were observed when rilpivirine 25 mg once daily was
taken during pregnancy. In the Phase III studies, lower rilpivirine
exposure, similar to that seen during pregnancy, has been
associated with an increased risk of virological failure, therefore
viral load should be monitored closely. Alternatively, switching to
another ART regimen could be considered.
Important information about some of the ingredients of
EDURANT
EDURANT contains lactose. Patients with rare hereditary problems of
galactose intolerance, the Lapp lactase deficiency or
glucose-galactose malabsorption should not take this medicinal
product.
Undesirable effects
During the clinical development program (1,368 patients in the
Phase III controlled trials TMC278-C209 (ECHO) and TMC278-C215
(THRIVE)), 55.7% of subjects experienced at least one adverse drug
reaction. The most frequently reported adverse drug reactions
(ADRs) (≥ 2%) that were at least of moderate intensity
were depression (4.1%), headache (3.5%), insomnia (3.5%), rash
(2.3%), and abdominal pain (2.0%). The most frequent serious
treatment-related ADRs were reported in 7 (1.0%) patients receiving
rilpivirine. The median duration of exposure for patients in the
rilpivirine arm and efavirenz arm was 104.3 and 104.1 weeks,
respectively. Most ADRs occurred in the first 48 weeks of
treatment.
Selected treatment emergent clinical laboratory abnormalities
(grade 3 or grade 4), considered as ADRs, reported in
EDURANT treated patients were increased pancreatic amylase (3.8%),
increased AST (2.3%), increased ALT (1.6%), increased LDL
cholesterol (fasted, 1.5%), decreased white blood cell count
(1.2%), increased lipase (0.9%), increased bilirubin (0.7%),
increased triglycerides (fasted, 0.6%), decreased haemoglobin
(0.1%), decreased platelet count (0.1%), and increased total
cholesterol (fasted, 0.1%).
Tabulated list of adverse reactions is available in the full
information leaflet.
Description of selected adverse reactions
Immune reactivation syndrome
In HIV infected patients with severe immune deficiency at the time
of initiation of combination antiretroviral therapy (CART), an
inflammatory reaction to asymptomatic or residual opportunistic
infections may arise. Autoimmune disorders (such as Graves' disease
and autoimmune hepatitis) have also been reported; however, the
reported time to onset is more variable and these events can occur
many months after initiation of treatment.
Breast-feeding
It is not known whether rilpivirine is excreted in human milk.
Rilpivirine is excreted in the milk of rats. Because of both the
potential for HIV transmission and the potential for adverse
reactions in breastfed infants, mothers should be instructed not to
breast-feed if they are receiving rilpivirine.
About ViiV Healthcare
ViiV Healthcare is a global specialist HIV company established in
November 2009 by GlaxoSmithKline plc (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
GlaxoSmithKline plc (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.
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ViiV Healthcare media enquires:
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Sofia
Kalish (Global)
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+44 (0)
7341079531
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(London)
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GSK enquiries:
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Media enquiries:
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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
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+44 (0)
20 8047 5502
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(London)
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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
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+1 202
603 5003
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(Washington
DC)
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Analyst/Investor enquiries:
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Sarah
Elton-Farr
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+44 (0)
20 8047 5194
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(London)
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Sonya
Ghobrial
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+44 (0)
7392 784784
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(Consumer)
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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
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+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.
Registered in England & Wales:
No.
3888792
Registered Office:
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References
[1] Vocabria EU Summary of
Product Characteristics.
[2] De Los Rios P, Okoli
C, Castellanos C et al. Treatment aspirations and
attitudes towards innovative
medications
among people living with HIV in 25 countries. Popul. Med.
2020;2(July):23
[3] De Los Rios P, Okoli
C, Castellanos C et al. Physical, Emotional and Psychosocial
Challenges Associated with Daily Dosing of HIV Medications and
Their Impact on Indicators of Quality of Life: Findings from the
Positive Perspectives Study. AIDS and Behavior.
2020
[4] 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
[5] 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
[6] Overton ET et.
al. Cabotegravir and rilpivirine every 2 months is non
inferior to monthly: ATLAS-2M study. Presented at CROI
2020: Available at: https://www.croiconference.org/abstract/cabotegravir-rilpivirine-every-2-months-is-noninferior-to-monthly-atlas-2m-study/.
Accessed September 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: December
21, 2020
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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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