a3642c
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 October 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: 16 October 2020, London UK - LSE announcement
ViiV Healthcare receives positive CHMP opinion for long-acting
regimen for the treatment of HIV
●
ViiV Healthcare's Vocabria (cabotegravir injection) used in
combination with Janssen Pharmaceutical Companies of Johnson &
Johnson's Rekambys (rilpivirine injection) reduces treatment dosing
days from 365 to 12 or 6 per year
●
Long-acting regimen is based on co-administration of cabotegravir
and rilpivirine injections once-monthly or once every 2-months to
treat HIV-1
●
Vocabria (cabotegravir) tablets for use as an oral lead-in therapy
with Edurant (rilpivirine tablets) prior to starting the
long-acting regimen also receives positive CHMP
opinion
London, 16 October 2020 - ViiV Healthcare, the global specialist HIV
company majority owned by GSK, with Pfizer Inc. and Shionogi
Limited as shareholders, today announced that the Committee for
Medicinal Products for Human Use (CHMP) of the European Medicines
Agency's (EMA) has issued a positive opinion recommending marketing
authorisation for Vocabria (cabotegravir injection and tablets) in
combination with Rekambys (rilpivirine injection) and Edurant
(rilpivirine tablets), for the treatment of Human
Immunodeficiency Virus type 1 (HIV-1) infection in adults who are
virologically suppressed (HIV-1 RNA less than 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 non-nucleoside reverse transcriptase inhibitor (NNRTI) and
integrase inhibitor (INI) class.[1]
Deborah Waterhouse, CEO, ViiV Healthcare,
said "Today's positive
CHMP opinion marks an important step in providing a new option that
changes the treatment experience for people living with HIV across
Europe. Vocabria injection used in combination with Rekambys has
the potential to ease the day-to-day burden of HIV by offering
significantly less frequent dosing from 365 days with oral regimens
to 12 or 6 treatments per year. Through our innovative
R&D, we are now one step closer to offering an HIV medicine in
Europe with a novel route of administration and dosing schedule
compared to other therapies. We're proud to be providing different
treatment options that meet the diverse needs of the HIV
community."
If approved, 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 across Europe.
This treatment will offer people living with HIV an option with
significantly less frequent dosing and comparable efficacy to daily
oral regimens. Cabotegravir and rilpivirine
injections are administered as two intramuscular (IM)
injections in the buttocks during the same visit at a specialist
clinic by a healthcare professional. 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.
The Marketing Authorisation Application (MAA) for cabotegravir
injection and tablets is based on the pivotal phase III ATLAS
(Antiretroviral Therapy as Long-Acting Suppression), FLAIR (First
Long-Acting Injectable Regimen) and ATLAS-2M studies.
The ATLAS and FLAIR studies included more than 1,100 participants
from 16 countries.[2],[3] The
studies demonstrated that cabotegravir and rilpivirine when
injected intramuscularly in the buttocks, once-monthly, was as
effective as continuing their daily, oral, antiretroviral regimens
in maintaining viral suppression throughout the 48-week study
period. The long-acting regimen was preferred by approximately
9 out of 10 patients who switched to cabotegravir and rilpivirine
long-acting in the ATLAS and FLAIR studies over their previous
daily oral therapy.*
In both studies, the most common adverse reactions (Grades 1 to 4)
observed in ≥ 2% of participants receiving cabotegravir and
rilpivirine were injection site reactions, pyrexia, fatigue,
headache, musculoskeletal pain, nausea, sleep disorders, dizziness,
rash, and diarrhoea. Over the 48-week study period, a total
of 4% of participants discontinued cabotegravir and rilpivirine due
to adverse events.[4]
------
*
●
The results are descriptive in nature and should not be used to
infer clinical significance. Results are descriptive and
reflect preferences shown by those entering into clinical trials of
long-acting therapy. They do not imply that PLHIV in general would
prefer long-acting therapy
●
In the pooled exploratory analysis in the ITT-E population:
patients responded to the preference question at Week 48 (59
patients did not). 88% (523/591) preferred cabotegravir and
rilpivirine long-acting vs. 2% (9/591) who preferred their previous
daily oral therapy.
●
Patient preference data is collected from clinical trial
participants randomised to long-acting arm, completing a
single-item question assessing their preference for cabotegravir
and rilpivirine long acting compared to daily oral ART medication
they were receiving prior to entry in the ATLAS and FLAIR
studies
48-week data from the pivotal ATLAS-2M
study were also included in the MAA to support the use of
cabotegravir and rilpivirine once every 2-months. Results from the
study showed the antiviral activity and safety of long-acting
cabotegravir and rilpivirine injections administered once every
2-months was non-inferior to long-acting cabotegravir and
rilpivirine injections administered once-monthly in virologically
suppressed adults living with HIV-1 infection over a 48-week
period. In the ATLAS-2M study rates of serious adverse
events (SAEs) (27/522 [5.2%]) and withdrawals due to adverse events
(AEs) (12/522 [2.3%]) at 48 weeks were low and were similar to
those experienced in the one month arm (SAEs: 19/523 [3.6%],
withdrawals due to AEs 13/523 [2.5%]).[5]
The Patient Reported Outcomes data from the ATLAS-2M study showed
high levels of treatment satisfaction and
acceptance,* with
98% (n=300/306) of participants who were randomised to receive an
oral lead-in followed by once every 2-months dosing preferring
treatment once every 2-months compared to daily oral treatment
(oral lead-in). Results indicate that administration frequency and
convenience were the most common reasons for preferring treatment
every 2-months.
ViiV Healthcare's mission is to ensure that no one living with HIV
is left behind. As the only pharmaceutical company solely focused
on HIV and AIDS, ViiV Healthcare is working to deliver a broad
range of treatments that meet the needs of a wide variety of PLHIV.
The company invest in R&D programmes that continuously push the
boundaries to provide a portfolio of innovative treatment options
that will help make a difference to the lives of PLHIV.
Cabotegravir and rilpivirine has been co-developed as part of
a collaboration with Janssen Pharmaceutical Companies of Johnson
& Johnson and builds on ViiV Healthcare's industry leading
portfolio, centred on delivering innovative medicines for the HIV
community.
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. If approved, cabotegravir injection and tablets
will be marketed as Vocabria to be used with Janssen's Rekambys
(rilpivirine injection) and Edurant (rilpivirine
tablets).
Once-monthly dosing of cabotegravir and rilpivirine has been
approved by Health Canada as a co-pack with two injectable
medicines under the brand name Cabenuva, for the treatment of HIV-1
infection in adults who are virologically stable and suppressed.
Vocabria (cabotegravir) oral tablets have also been approved by
Health Canada. 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 approved 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 (brand name Rekambys) 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.
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 rilpirivine
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 (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.
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ViiV Healthcare media enquires:
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Patricia
O'Connor (Global)
Audrey
Abernathy
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+44
(0) 7469 375019
+1
916054521
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(London)
(US)
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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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Simon
Moore
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+44 (0)
20 8047 5502
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(London)
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Mary
Hinks-Edwards
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+44 (0)
20 8047 5502
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(London)
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Eleanor
Bunch
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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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Danielle
Smith
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+44 (0)
20 8047 0932
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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
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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 Q2 Results and
any impacts of the COVID-19 pandemic.
Registered in England &
Wales:
No.
3888792
Registered
Office:
980
Great West Road
Brentford,
Middlesex
TW8
9GS
[1] European Medicines
Agency. Vocabria Summary of Opinion. Available at [INSERT LINK].
Accessed September 2020.
[2] 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.
[3] 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.
[4] Overton ET, Orkin C, Swindell S, et al. Monthly
long-acting cabotegravir and rilpivirine is non-inferior to oral
ART as maintenance therapy for HIV-1 infection: Week 48 pooled
analysis from the phase 3 ATLAS and FLAIR studies. Presented at IAS
2019.
[5] 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/ (Last
Accessed August 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: October
16, 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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