REG - GlaxoSmithKline PLC - FDA update: Cabenuva oral lead-in now optional

GSKAnnouncement

24/03/2022 14:00

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RNS Number : 9397F  GlaxoSmithKline PLC  24 March 2022

 

Issued: 24 March 2022, London UK

 

ViiV Healthcare announces label update for its long-acting HIV treatment,
Cabenuva (cabotegravir, rilpivirine), to be initiated with or without an oral
lead-in period

US FDA approval of updated label streamlines the initiation process for the
first and only complete long-acting HIV treatment by allowing people to start
directly with injections

 

London, 24 March 2022 - 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 a label update for Cabenuva (cabotegravir,
rilpivirine) making the oral lead-in with cabotegravir and rilpivirine tablets
optional. Oral cabotegravir and rilpivirine can be taken for a month to assess
tolerability to the medicines prior to initiating cabotegravir and rilpivirine
injections, a regimen co-developed as part of a collaboration with the Janssen
Pharmaceutical Companies of Johnson & Johnson, but this oral lead-in is
now optional after clinical trial data demonstrated similar safety and
efficacy profiles for both initiation methods (with or without the oral
lead-in).(1, 2)

 

Cabenuva is the first and only complete long-acting HIV treatment regimen and
is approved in the US as a once-monthly or every-two-month treatment for HIV-1
in virologically suppressed adults.(1) It contains ViiV Healthcare's
cabotegravir extended-release injectable suspension in a single-dose vial and
rilpivirine extended-release injectable suspension in a single-dose vial, a
product of Janssen Sciences Ireland Unlimited Company, one of the Janssen
Pharmaceutical Companies of Johnson & Johnson.

 

Lynn Baxter, Head of North America at ViiV Healthcare, said: "Since launching
Cabenuva, we have been keenly focused on optimising the user experience for
both people living with HIV and healthcare providers. Today's label update for
the optional oral lead-in provides a streamlined initiation process for the
regimen by allowing people to start directly on long-acting injections and
underscores ViiV Healthcare's ongoing commitment to providing innovative
treatment options that address the evolving needs of the HIV community."

 

This US FDA approval is based on the FLAIR phase III trial Week-124 results,
which showed there were similar outcomes regarding maintenance of virologic
suppression, safety, tolerability and pharmacokinetics in people starting
cabotegravir and rilpivirine injections with or without the oral lead-in. (2)

 

About Cabenuva (cabotegravir, rilpivirine)

Cabenuva is indicated as a complete regimen for the treatment of HIV-1
infection in adults to replace the current antiretroviral regimen in those who
are virologically suppressed (HIV-1 RNA <50 c/ml) on a stable
antiretroviral regimen with no history of treatment failure and with no known
or suspected resistance to either cabotegravir or rilpivirine.

 

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
Unlimited Company. Rilpivirine is approved in the US as a 25mg tablet taken
once a day to treat HIV-1 in combination with other antiretroviral agents in
antiretroviral treatment-naïve patients 12 years of age and older and
weighing at least 35kg with a viral load ≤100,000 HIV RNA c/ml.

 

INSTIs 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 disease. Rilpivirine is an NNRTI that works by
interfering with an enzyme called reverse transcriptase, which stops the virus
from multiplying.

 

Trademarks are owned by or licensed to the ViiV Healthcare group of companies.

 

Important Safety Information for Cabenuva (cabotegravir 200mg/mL; rilpivirine
300mg/mL) extended-release injectable suspensions

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, bronchospasm, agitation, abdominal cramping,
rash/urticaria, dizziness, flushing, sweating, oral numbness, changes in blood
pressure, and pain (e.g., back and chest). 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. The suspensions should be injected slowly via
intramuscular injection and 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 or
every-2-month injection dosing schedule because non-adherence 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 when dosed
monthly and no later than 2 months after the final injections of Cabenuva when
dosed every 2 months. 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 EDURANT

·      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
(https://gsksource.com/pharma/content/dam/GlaxoSmithKline/US/en/Prescribing_Information/Cabenuva/pdf/CABENUVA-PI-PIL-IFU2-IFU3.PDF)
.

 

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 aims are to take a deeper and broader interest in
HIV and 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
(http://www.viivhealthcare.com/) .

 

About GSK

GSK is a science-led global healthcare company. For further information please
visit https://www.gsk.com/en-gb/about-us (http://www.gsk.com/en-gb/about-us)
.

 ViiV Healthcare enquiries:
 Media enquiries:               Catherine Hartley  +44 7909 002 403  (London)
                                Audrey Abernathy   +1 919 605 4521   (North Carolina)

 

 GSK enquiries:
 Media enquiries:             Tim Foley         +44 (0) 20 8047 5502    (London)
                              Dan Smith         +44 (0) 20 8047 5502    (London)
                              Kathleen Quinn    +1 202 603 5003         (Washington DC)

 Analyst/Investor enquiries:  Nick Stone        +44 (0) 7717 618834     (London)
                              Sonya Ghobrial    +44 (0) 7392 784784     (Consumer)
                              James Dodwell     +44 (0) 20 8047 2406    (London)

                              Mick Readey       +44 (0) 7990 339653     (London)
                              Josh Williams     +44 (0) 7385 415719     (London)
                              Jeff McLaughlin   +1 215 751 7002         (Philadelphia)

Cautionary statement regarding forward-looking statements

GlaxoSmithKline plc cautions investors that any forward-looking statements or
projections made by GlaxoSmithKline plc, 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 in the Company's Annual Report on Form
20-F for 2021 and any impacts of the COVID-19 pandemic.

 

Registered in England & Wales:

GlaxoSmithKline plc                 ViiV Healthcare Limited

No. 3888792
No. 06876960

 

Registered Office:

980 Great West Road

Brentford, Middlesex

TW8 9GS

 

 

References

 

1.     Cabenuva (cabotegravir, rilpivirine) Prescribing Information. US
Approval March 2022.

2.     D'Amico R, Orkin C, Morell EB, et al. Safety and efficacy of
cabotegravir + rilpivirine long-acting with and without oral lead-in: FLAIR
Week 124 results. Presented at HIV Glasgow 2020.

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