Tentative approval will help enhance access to
WHO-recommended paediatric regimen with the goal of improved
adherence of HIV treatment for children in low- and middle-income
countries
PITTSBURGH and BANGALORE, India, Sept. 5,
2023 /PRNewswire/ -- Viatris Inc. (NASDAQ:
VTRS), a global healthcare company, today announced U.S. Food
and Drug Administration (FDA) tentative approval for a New Drug
Application for abacavir 60 mg/dolutegravir 5 mg/lamivudine 30 mg
tablets for oral suspension for the treatment of HIV-1 infection in
paediatric patients.
The World Health Organization (WHO) recommends
abacavir/dolutegravir/lamivudine as a preferred first-line regimen
for paediatric patients. According to the Joint United Nations
Programme on HIV/AIDS (UNAIDS), treatment coverage for children and
adolescents lags behind adults. Some 660,000 children living with
HIV – about 43 percent of the estimated total 1.5 million [1.2
million–2.1 million] children living with HIV – did not receive
antiretroviral (ARV) therapy in 2022. Accordingly, children
accounted for 13 per cent of AIDS-related deaths in 2022, even
though they comprise only about 4 percent of people living with
HIV.
The fixed-dose combination of abacavir 60 mg/dolutegravir 5
mg/lamivudine 30 mg tablets for oral suspension is indicated for
the treatment of HIV-1 infection in paediatric patients weighing at
least 6 kg. The fixed-dose combination tablets for oral suspension
are strawberry-flavoured. Historically, it has been challenging to
treat paediatric HIV patients because children require special
medicine formulations.
The FDA's tentative approval through the President's Emergency
Plan for AIDS Relief (PEPFAR) program means the formulation meets
all the agency's quality, safety, and efficacy standards. Viatris
has signed a licensing agreement for paediatric dolutegravir from
the Medicines Patent Pool (MPP) and development agreement with ViiV
Healthcare (ViiV) and the Clinton Health Access Initiative (CHAI)
for producing and distributing the fixed-dose combination of
abacavir/ dolutegravir/lamivudine.
Rakesh Bamzai, President of
India, Emerging Asia & Access
Markets at Viatris, said, "At Viatris, we have expanded access
at scale to high-quality HIV/AIDS treatment for more than a decade.
Over the years, we have continued to seek improvements to existing
molecules to better meet patient needs – we have introduced novel
heat-stable generic formulations, more convenient packaging
options, and paediatric therapies. We have also built strong
partnerships with multiple stakeholders to improve access to ARVs,
with particular attention to vulnerable populations like children.
The approval of this single tablet regimen – the fixed-dose
combination of abacavir 60 mg/dolutegravir 5 mg/lamivudine 30
mg - will reduce the pill burden for children living with
HIV."
This milestone supports the company's sustainability goal to
provide ARV therapy equivalent to a total of 30 million patients,
including more than 2 million children living with HIV/AIDS,
between 2022 and the end of 2025.
The fixed-dose combination of abacavir/dolutegravir/lamivudine
is approved for once-daily treatment of paediatric patients
weighing at least 6 kg to <25 kg with HIV-1 infection and the
recommended dose of the fixed-dose combination of
abacavir/dolutegravir/lamivudine tablets for oral suspension is
determined according to weight. The fixed-dose combination of
abacavir/dolutegravir/lamivudine are contraindicated in
patients with a prior hypersensitivity reaction to abacavir and in
HLAB*5701-positive patients. The tentative approval facilitates
regulatory authority submissions, production and distribution of
the new child friendly formulation across 123 low- and
middle-income countries as per the license agreement.
About the fixed-dose combination of
abacavir/dolutegravir/lamivudine tablets for oral
suspension
Abacavir/dolutegravir/lamivudine is a fixed-dose
combination containing two nucleoside reverse transcriptase
inhibitors (NRTIs) and integrase strand transfer inhibitor (INSTI).
NRTIs interfere with the action of the reverse transcriptase enzyme
and INSTI interferes with the action of integrase enzyme to prevent
the virus from replicating. All patients with HIV-1 should be
tested for the presence of hepatitis B virus (HBV) prior to or when
initiating the fixed-dose combination of abacavir 60
mg/dolutegravir 5 mg/lamivudine 30 mg as severe acute
exacerbations of HBV have been reported in patients who are
co-infected with HBV and HIV-1 and have discontinued the
medication.
Abacavir/dolutegravir/lamivudine was approved in the US on
30 March 2022 under the brand name
Triumeq PD.
Triumeq PD is registered trademark of the ViiV Healthcare group
of companies.
About Viatris
Viatris Inc. (NASDAQ: VTRS) is a global healthcare company
empowering people worldwide to live healthier at every stage of
life. We provide access to medicines, advance sustainable
operations, develop innovative solutions and leverage our
collective expertise to connect more people to more products and
services through our one-of-a-kind Global Healthcare Gateway®.
Formed in November 2020, Viatris
brings together scientific, manufacturing and distribution
expertise with proven regulatory, medical, and commercial
capabilities to deliver high-quality medicines to patients in more
than 165 countries and territories. Viatris' portfolio comprises
more than 1,400 approved molecules across a wide range of
therapeutic areas, spanning both non-communicable and infectious
diseases, including globally recognized brands, complex generic and
branded medicines, and a variety of over-the-counter consumer
products. With more than 38,000 colleagues globally, Viatris is
headquartered in the U.S., with global centers in Pittsburgh, Shanghai and Hyderabad, India. Learn more at viatris.com
and investor.viatris.com, and connect with us on Twitter, LinkedIn,
Instagram and YouTube.
Important Safety Information (ISI) for the fixed-dose
combination of abacavir 600 mg/dolutegravir 50 mg/lamivudine 300 mg
tablets and the fixed-dose combination of abacavir 60
mg/dolutegravir 5 mg/lamivudine 30 mg tablets for oral
suspension.
INDICATION
The fixed-dose combination of abacavir 60 mg/dolutegravir 5
mg/lamivudine 30 mg tablets for oral suspension is indicated
for the treatment of HIV-1 infection in paediatric patients aged at
least 3 months weighing at least 6 kg. to less than 25 kgs.
Limitations of Use:
The fixed-dose combination of abacavir 60 mg/dolutegravir 5
mg/lamivudine 30 mg tablets for oral suspension is not
recommended in patients with resistance-associated integrase
substitutions or clinically suspected INSTI resistance because the
dose of dolutegravir in the fixed-dose combination of abacavir 60
mg/dolutegravir 5 mg/lamivudine 30 mg is insufficient in these
subpopulations. See full prescribing information for
dolutegravir.
IMPORTANT SAFETY INFORMATION
BOXED WARNING: HYPERSENSITIVITY REACTIONS AND EXACERBATIONS OF
HEPATITIS B VIRUS (HBV)
Hypersensitivity Reactions:
Serious and sometimes fatal hypersensitivity reactions, with
multiple organ involvement, have occurred with abacavir, a
component of the fixed-dose combination of abacavir 60
mg/dolutegravir 5 mg/lamivudine 30 mg.
Patients who carry the HLA-B*5701 allele are at a higher risk of
experiencing a hypersensitivity reaction to abacavir, although
hypersensitivity reactions have occurred in patients who do not
carry the HLA-B*5701 allele.
The fixed-dose combination of abacavir 60 mg/dolutegravir 5
mg/lamivudine 30 mg are contraindicated in patients with a
prior hypersensitivity reaction to abacavir and in
HLAB*5701-positive patients. All patients should be screened for
the HLA-B*5701 allele prior to initiating therapy or re-initiation
of therapy with the fixed-dose combination of abacavir 60
mg/dolutegravir 5 mg/lamivudine 30 mg unless patients have a
previously documented HLA-B*5701 allele assessment.
Discontinue the fixed-dose combination of abacavir 60
mg/dolutegravir 5 mg/lamivudine 30 mg immediately if a
hypersensitivity reaction is suspected, regardless of HLA-B*5701
status and even when other diagnoses are possible.
Following a hypersensitivity reaction to the fixed-dose
combination of abacavir 60 mg/dolutegravir 5 mg/lamivudine 30 mg,
NEVER restart the fixed-dose combination of abacavir 60
mg/dolutegravir 5 mg/lamivudine 30 mg tablets for oral suspension
or any other abacavir-containing product.
Exacerbations of Hepatitis B:
All patients with HIV-1 should be tested for the presence of
hepatitis B virus (HBV) prior to or when initiating the fixed-dose
combination of abacavir 60 mg/dolutegravir 5 mg/lamivudine 30 mg.
Emergence of lamivudine-resistant HBV variants associated with
lamivudine-containing antiretroviral regimens has been reported. If
the fixed-dose combination of abacavir 60 mg/dolutegravir 5
mg/lamivudine 30 mg is used in patients co-infected with HIV-1
and HBV, additional treatment should be considered for appropriate
treatment of chronic HBV; otherwise, consider an alternative
regimen.
Severe acute exacerbations of HBV have been reported in patients
who are co-infected with HBV and HIV-1 and have discontinued
lamivudine, a component of the fixed-dose combination of abacavir
60 mg/dolutegravir 5 mg/lamivudine 30 mg. Monitor hepatic function
closely in these patients and, if appropriate, initiate
anti-hepatitis B treatment.
Contraindications
Do not use the fixed-dose combination of abacavir 60
mg/dolutegravir 5 mg/lamivudine 30 mg in patients who have the
HLA-B*5701 allele.
Do not use the fixed-dose combination of abacavir 60
mg/dolutegravir 5 mg/lamivudine 30 mg in patients with previous
hypersensitivity reaction to abacavir, dolutegravir, or
lamivudine.
Do not use the fixed-dose combination of abacavir 60
mg/dolutegravir 5 mg/lamivudine 30 mg in patients receiving
dofetilide.
Do not use the fixed-dose combination of abacavir 60
mg/dolutegravir 5 mg/lamivudine 30 mg in patients with moderate or
severe hepatic impairment.
Warnings and precautions
Hypersensitivity Reactions:
Hypersensitivity reactions have been reported with dolutegravir and
were characterized by rash, constitutional findings, and sometimes
organ dysfunction, including liver injury.
Clinically, it is not possible to determine whether a
hypersensitivity reaction with the fixed-dose combination of
abacavir 60 mg/dolutegravir 5 mg/lamivudine 30 mg would be caused
by abacavir or dolutegravir.
Discontinue the fixed-dose combination of abacavir 60
mg/dolutegravir 5 mg/lamivudine 30 mg immediately if signs or
symptoms of hypersensitivity reactions develop, as a delay in
stopping treatment may result in a life-threatening reaction.
Clinical status, including liver aminotransferases, should be
monitored and appropriate therapy initiated.
Hepatotoxicity:
Hepatic adverse events have been reported, including cases of
hepatic toxicity (elevated serum liver biochemistries, hepatitis,
and acute liver failure), in patients receiving a
dolutegravir-containing regimen without pre-existing hepatic
disease or other identifiable risk factors.
Patients with underlying hepatitis B or C may be at increased
risk for worsening or development of transaminase elevations with
use of the fixed-dose combination of abacavir 60 mg/dolutegravir 5
mg/lamivudine 30 mg. In some cases, the elevations in transaminases
were consistent with immune reconstitution syndrome or hepatitis B
reactivation, particularly in the setting where anti-hepatitis
therapy was withdrawn.
Drug-induced liver injury leading to liver transplant has been
reported with the fixed-dose combination of
abacavir/dolutegravir/lamivudine.
Monitoring for hepatotoxicity is recommended.
Lactic Acidosis and Severe Hepatomegaly with
Steatosis:
Fatal cases have been reported with the use of nucleoside
analogues, including abacavir and lamivudine.
Discontinue the fixed-dose combination of abacavir 60
mg/dolutegravir 5 mg/lamivudine 30 mg if clinical or laboratory
findings suggestive of lactic acidosis or pronounced hepatotoxicity
develop, including hepatomegaly and steatosis in the absence of
marked transaminase elevations.
Embryo-Fetal Toxicity:
Assess the risks and benefits of the fixed-dose combination of
abacavir/dolutegravir/lamivudine and discuss with the patient
to determine if alternative treatments should be considered at the
time of conception through the first trimester of pregnancy due to
the risk of neural tube defects.
Pregnancy testing is recommended before use of the fixed-dose
combination of abacavir/dolutegravir/lamivudine. Adolescents and
adults of childbearing potential should be counseled on the
consistent use of effective contraception.
The fixed-dose combination of
abacavir/dolutegravir/lamivudine may be considered during the
second and third trimesters of pregnancy if the expected benefit
justifies the potential risk to the pregnant woman and the
fetus.
Adverse Reactions or Loss of Virologic Response Due to Drug
Interactions with concomitant use of the fixed-dose combination of
abacavir 60 mg/dolutegravir 5 mg/lamivudine 30 mg and other
drugs may occur (see Contraindications and Drug Interactions).
Immune Reconstitution Syndrome, including the occurrence of
autoimmune disorders with variable time to onset, has been reported
with the use of fixed-dose combination of abacavir 60
mg/dolutegravir 5 mg/lamivudine 30 mg.
Different Formulations Are Not Interchangeable:
The fixed-dose combination of abacavir 600 mg/dolutegravir 50
mg/lamivudine 300 mg tablets and the fixed-dose combination of
abacavir 60 mg/dolutegravir 5 mg/lamivudine 30 mg tablets for
oral suspension are not bioequivalent and are not interchangeable
on a milligram-per-milligram basis. If a patient switches from one
formulation to the other, the dose must be adjusted.
Myocardial Infarction (MI):
Several observational studies have reported an association with the
use of abacavir and the risk of MI; meta-analyses of randomized
controlled clinical trials did not show increased risk. To date,
there is no established biological mechanism to explain a potential
increase in risk. In totality, the available data show
inconsistency; therefore, evidence for a causal relationship
between abacavir and the risk of MI is inconclusive.
The underlying risk of coronary heart disease should be
considered when prescribing antiretroviral therapies, including
abacavir, and action taken to minimize all modifiable risk factors
(e.g., hypertension, hyperlipidemia, diabetes mellitus,
smoking).
Adverse reactions:
The most common adverse reactions (incidence ≥2%, Grades 2-4) in
treatment-naïve adults receiving the fixed-dose combination of
abacavir 600 mg/dolutegravir 50 mg/lamivudine 300 mg tablets
were insomnia (3%), headache (2%), and fatigue (2%).
Drug interactions:
Consult the full Prescribing Information for more information on
potentially significant drug interactions.
Use in specific populations:
Pregnancy: Assess the risks and benefits of the fixed-dose
combination of abacavir 600 mg/dolutegravir 50 mg/lamivudine 300
mg tablets and discuss with the patient to determine if an
alternative treatment should be considered at the time of
conception through the first trimester or if pregnancy is confirmed
in the first trimester due to the risk of neural tube defects.
Lactation: Breastfeeding is not recommended due to the potential
for HIV-1 transmission, developing viral resistance in HIV-positive
infants, and adverse reactions in a breastfed infant.
Impaired Renal Function: the fixed-dose combination of abacavir
60 mg/dolutegravir 5 mg/lamivudine 30 mg are not recommended
for patients with creatinine clearance <30 mL/min. Patients with
a sustained creatinine clearance between 30 and 49 mL/min should be
monitored for hematologic toxicities, which may require a dosage
adjustment of lamivudine as an individual component.
Impaired Hepatic Function: If a dose reduction of abacavir is
required for patients with mild hepatic impairment, then the
individual components of the fixed-dose combination of abacavir 60
mg/dolutegravir 5 mg/lamivudine 30 mg tablets should be
used.
References:
- Consolidated guidelines on HIV prevention, testing, treatment,
service delivery and monitoring: Recommendations for a public
health approach
- The path that ends AIDS: UNAIDS Global AIDS Update
2023
Forward-Looking Statements
This press release includes
statements that constitute "forward-looking statements." These
statements are made pursuant to the safe harbor provisions of the
Private Securities Litigation Reform Act of 1995. Such forward
looking statements may include statements that tentative approval
will help enhance access to WHO-recommended paediatric regimen with
the goal of improved adherence of HIV treatment for children in
low- and middle-income countries; the approval of this single
tablet regimen – the fixed-dose combination of abacavir 60
mg/dolutegravir 5 mg/lamivudine 30 mg - will reduce the pill burden
for children living with HIV; and the milestone supports the
company's sustainability goal to provide ARV therapy equivalent to
a total of 30 million patients, including more than 2 million
children living with HIV/AIDS, between 2022 and the end of 2025.
Factors that could cause or contribute to such differences include,
but are not limited to: actions and decisions of healthcare and
pharmaceutical regulators; changes in healthcare and pharmaceutical
laws and regulations in the U.S. and abroad; any regulatory, legal
or other impediments to Viatris' ability to bring new products to
market, including but not limited to "at-risk" launches; Viatris'
or its partners' ability to develop, manufacture, and commercialize
products; the possibility that the Company may be unable to realize
the intended benefits of, or achieve the intended goals or outlooks
with respect to, its strategic initiatives; the possibility that
the Company may be unable to achieve expected benefits, synergies
and operating efficiencies in connection with acquisitions,
divestitures, or its global restructuring program, within the
expected timeframe or at all; impairment charges or other losses
related to the divestiture or sale of businesses or assets; the
Company's failure to achieve expected or targeted future financial
and operating performance and results; the potential impact of
public health outbreaks, epidemics and pandemics, including the
ongoing challenges and uncertainties posed by COVID-19; the scope,
timing and outcome of any ongoing legal proceedings, and the impact
of any such proceedings; any significant breach of data security or
data privacy or disruptions to our information technology systems;
risks associated with international operations; the ability to
protect intellectual property and preserve intellectual property
rights; changes in third-party relationships; the effect of any
changes in Viatris' or its partners' customer and supplier
relationships and customer purchasing patterns; the impacts of
competition; changes in the economic and financial conditions of
Viatris or its partners; uncertainties and matters beyond the
control of management, including general economic conditions,
inflation and exchange rates; failure to execute stock repurchases
consistent with current expectations; stock price volatility; and
the other risks described in Viatris' filings with the Securities
and Exchange Commission (SEC). Viatris routinely uses its website
as a means of disclosing material information to the public in a
broad, non-exclusionary manner for purposes of the SEC's Regulation
Fair Disclosure (Reg FD). Viatris undertakes no obligation to
update these statements for revisions or changes after the date of
this release other than as required by law.
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