REG - GlaxoSmithKline PLC - FDA approves ViiV Healthcare’s sNDA for Cabenuva

GSKAnnouncement

01/02/2022 13:45

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RNS Number : 3518A  GlaxoSmithKline PLC  01 February 2022

ViiV Healthcare announces US FDA approval of Cabenuva (cabotegravir,
rilpivirine) for use every two months, expanding the label of the first and
only complete long-acting HIV treatment

Cabenuva is now approved for administration as few as six times a year for
virologically suppressed adults living with HIV without prior treatment
failure or resistance to cabotegravir or rilpivirine

London, 1 February 2022 - ViiV Healthcare, the global specialist HIV company
majority-owned by GlaxoSmithKline plc (GSK), with Pfizer Inc. (Pfizer) and
Shionogi Limited (Shionogi) as shareholders, today announced that the US Food
and Drug Administration (FDA) approved Cabenuva (cabotegravir, rilpivirine)
for every-two-month dosing for the treatment of HIV-1 in virologically
suppressed adults (HIV-1 RNA less than 50 copies per millilitre  c/ml ) on a
stable regimen, with no history of treatment failure, and with no known or
suspected resistance to either cabotegravir or rilpivirine.

 

Cabenuva is the first and only complete long-acting HIV treatment regimen and
was first approved by the US FDA in January 2021 as a once-monthly 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. The US FDA approval allows
Cabenuva to be dosed monthly or every two months.

 

Lynn Baxter, Head of North America at ViiV Healthcare, said: "ViiV Healthcare
is pleased to continue our leadership in researching and developing
long-acting innovative HIV treatment options that address the evolving needs
of the HIV community. Today's approval is a remarkable achievement given where
HIV treatment was just a decade ago. We know some people living with HIV
struggle with taking daily oral pills, and Cabenuva may allow them to maintain
viral suppression while significantly reducing dosing to as few as six times a
year."

 

The US FDA approval of long-acting cabotegravir and rilpivirine for use every
two months is based on the global ATLAS-2M phase IIIb trial results, which
demonstrated that every-two-month dosing was non-inferior to once-monthly
dosing.(2) Non-inferiority was determined by comparing the proportion of
participants with plasma HIV-1 RNA ≥ 50 c/ml using the US FDA Snapshot
algorithm at Week 48 (Intent-to-Treat Exposed population), which showed that
the every-two-month arm (9/522  1.7% ) and once-monthly arm (5/523  1.0% )
were similarly effective (adjusted difference: 0.8%, 95% confidence interval
 CI : -0.6%, 2.2%). The study also found that rates of virologic suppression,
a key secondary endpoint, were similar for every-two-month dosing (492/522
 94.3% ) and once-monthly dosing (489/523  93.5% ) (adjusted difference: 0.8%,
95% CI: -2.1%, 3.7%). The most common adverse reactions (Grades 1 to 4)
observed in ≥2% of participants receiving long-acting cabotegravir and
rilpivirine were injection site reactions, pyrexia, fatigue, headache,
musculoskeletal pain, nausea, sleep disorders, dizziness, and rash. In
ATLAS-2M, the type and frequency of adverse reactions reported in participants
receiving long-acting cabotegravir and rilpivirine once monthly or every two
months for 48 weeks were similar. In the every-two-month arm, rates of serious
adverse events (SAEs: 27/522 5.2% ) and withdrawals due to adverse events
(AEs: 12/522  2.3% ) were low and similar to those experienced in the
once-monthly arm (SAEs: 19/523  3.6% , withdrawals due to AEs 13/523
 2.5% ).(2)

 

Turner Overton, MD, Professor, Department of Medicine at the University of
Alabama at Birmingham and ATLAS-2M Primary Investigator, said: "Many people
living with HIV face challenges with daily therapies and are interested in
alternative dosing options. In clinical trials, approximately nine out of
every ten trial participants preferred long-acting cabotegravir and
rilpivirine dosed every two months compared to daily oral cabotegravir and
rilpivirine taken as the oral lead-in per trial protocol. This preference data
highlights the meaningful impact long-acting regimens can have on the
treatment experience for the HIV community."

 

Patient preference data were collected from clinical trial participants who
received long-acting cabotegravir and rilpivirine. In a pooled analysis of
this intent-to-treat exposed population with no prior experience with
long-acting cabotegravir and rilpivirine, 327 patients completed a single-item
question at Week 48, and 92% (300/327) preferred every-two-month injections
compared with one per cent (4/327) who preferred oral cabotegravir and
rilpivirine that was taken as the required oral lead-in. These results are
descriptive in nature and should not be used to infer clinical
significance.(3)

 

About ATLAS-2M (NCT03299049)

The ATLAS-2M phase IIIb trial is an ongoing, randomised, open-label,
active-controlled, multicentre, parallel-group trial designed to assess the
non-inferior antiviral activity and safety of long-acting cabotegravir and
rilpivirine administered every eight weeks (every two months, 3ml dose of each
medicine) compared to every four weeks (once monthly, 2ml dose of each
medicine) over a 48-week treatment period in 1,045 adults living with
HIV-1.(2) Subjects were required to be virologically suppressed for six
months or greater, on a first or second antiretroviral regimen, with no prior
virologic failure. The primary outcome measure for the trial was the
proportion of participants with HIV-1 RNA ≥ 50 c/ml at Week 48 using the US
FDA Snapshot algorithm (intent-to-treat exposed population). ATLAS-2M is part
of ViiV Healthcare's extensive and innovative clinical trial programme. It is
being conducted at research centres in Australia, Argentina, Canada, France,
Germany, Italy, Mexico, Russia, South Africa, South Korea, Spain, Sweden and
the United States.

 

For further information, please
see https://clinicaltrials.gov/ct2/show/NCT03299049
(https://clinicaltrials.gov/ct2/show/NCT03299049) .

 

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. 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.

 

Long-acting cabotegravir and rilpivirine are approved for use every two months
in Canada under the name Cabenuva and in the EU as Vocabria and Rekambys.

 

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

 

Important Safety Information for Cabenuva (cabotegravir; rilpivirine)
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.

·      The most common injection site reactions (grades 1-3, ≥1%) were
pain/discomfort, nodules, induration, swelling, erythema, pruritus,
bruising/discoloration, warmth, and hematoma

 

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/NYSE: 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 ViiV Healthcare's Patient Assistance Program

ViiV Healthcare is committed to providing assistance to eligible people living
with HIV in the US who need our medicines. ViiV Healthcare's centralised
service, ViiV Connect, provides comprehensive information on access and
coverage to help patients living in the US get their prescribed ViiV
Healthcare medicines whether they are insured, underinsured or uninsured. ViiV
Connect provides one-on-one support from dedicated access coordinators, as
well as having an integrated website, one site with many resources, including
a portal. For more information on ViiV Connect, visit www.viivconnect.com
(http://www.viivconnect.com/) .

 

About GSK

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

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

 

 GSK enquiries:
 Media enquiries:               Tim Foley          +44 (0) 20 8047 5502    (London)
                                Madeleine Breckon  +44 (0) 20 8047 5502    (London)
                                Kristen Neese      +1 804 217 8147         (Philadelphia)
                                Kathleen Quinn     +1 202 603 5003         (Washington DC)

 Analyst/Investor enquiries:    Nick Stone         +44 7717 618834         (London)
                                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)
                                Frannie DeFranco   +1 215 751 4855         (Philadelphia)

Cautionary statement regarding forward-looking statements

GSK cautions investors that any forward-looking statements or projections made
by GSK, including those made in this announcement, are subject to risks and
uncertainties that may cause actual results to differ materially from those
projected. Such factors include, but are not limited to, those described in
the Company's Annual Report on Form 20-F for 2020, GSK's Q3 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

 

 

References

 

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

2.     Overton E, Richmond G, Rizzardini G, et al. Long-acting
cabotegravir and rilpivirine dosed every 2 months in adults with HIV-1
infection (ATLAS-2M), 48-week results: a randomized, multicentre, open-label,
phase 3b non-inferiority study. Lancet, 396(10267): 1994-2005. 9 December
2020. doi: 10.1016/S0140-6736(20)32666-0.

3.     Chounta, Vasiliki et al. "Patient-Reported Outcomes Through 1 Year
of an HIV-1 Clinical Trial Evaluating Long-Acting Cabotegravir and Rilpivirine
Administered Every 4 or 8 Weeks (ATLAS-2M)." The patient,
10.1007/s40271-021-00524-0. 31 May. 2021, doi:10.1007/s40271-021-00524-0

 

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