Samsung Bioepis & Organon Announce FDA Acceptance of Supplemental Biologics License Application (sBLA) for Interchangeability Designation for HADLIMA™ (adalimumab-bwwd), a Biosimilar to Humira®

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November 7, 2023 4:15 pm EDT

  • sBLA based on Phase 4 study which assessed pharmacokinetic similarity
    between two treatment groups: multi-switching group alternating between
    Humira and high-concentration HADLIMA vs. Humira-continued group
  • Filing acceptance reinforces Samsung Bioepis and Organon’s
    commitment to provide better access to biologic medicines for patients in
    the United States

INCHEON, Korea & JERSEY CITY, N.J. –November 07, 2023 – Samsung Bioepis Co., Ltd. and Organon & Co. (NYSE: OGN) today announced
that the U.S. Food and Drug Administration (FDA) has accepted for review the
Supplemental Biologics License Application (sBLA) for the interchangeability
designation for HADLIMA™ (adalimumab-bwwd) injection 40 mg/0.4 mL, a
biosimilar to Humira® (adalimumab). The sBLA was submitted to
the FDA by Samsung Bioepis in August 2023.

The sBLA submission was based on clinical data from the Phase 4, randomized,
double-blind, 1:1 ratio, parallel-group, multiple-dose, active comparator,
multicenter clinical study (NCT05510063) to assess the pharmacokinetic similarity between two treatment groups:
patients with moderate to severe plaque psoriasis who switched multiple times
between high-concentration formulations of Humira and HADLIMA versus patients
receiving Humira continuously.1

“Following our announcement on the interchangeability study’s
topline results in August, we are excited to share the progress on this sBLA
filing on interchangeability. This filing acceptance is a reinforcement of our
commitment to provide better access to biologic medicines for patients in the
United States,” said Byoung In Jung, Vice President and Regulatory
Affairs Team Leader at Samsung Bioepis. “We will continue to drive our
goal of realizing the value of biosimilars for patients and contributing to
the sustainability of healthcare systems.”

“An interchangeability designation may play a role beyond enabling
pharmacy substitution. We believe that interchangeability could help increase
physician confidence with prescribing biosimilars, especially in the
high-concentration formulation which is used by the majority of Humira
patients. We remain committed to helping more patients access biosimilar
alternatives,” said Jon Martin, Head, US Biosimilars at Organon.

HADLIMA (adalimumab-bwwd) was first approved by the FDA in July 2019 as a
low-concentration (40 mg/0.8 mL) formulation of prefilled syringe and
prefilled autoinjector. The high-concentration (40 mg/0.4 mL) formulation of
prefilled syringe and prefilled autoinjector of HADLIMA was approved in August
2022. HADLIMA was introduced into the US commercial market on July 1, 2023 and
is marketed by Organon.

About Interchangeability

Both biosimilars and interchangeable biosimilars have no clinically meaningful
differences in safety, purity, and potency as the original biologic for
approved indications.2 To be designated as “interchangeable,”
information must be submitted to show that:

  • the biological product is biosimilar to the reference product,
  • the biological product can be expected to produce the same clinical result
    as the reference product in any given patient, and
  • for a biological product that is administered more than once to an
    individual, the risk in terms of safety or diminished efficacy of
    alternating or switching between use of the biological product and the
    reference product is not greater than the risk of using the reference
    product without such alternation or switch.3

Once a biosimilar product is designated as an interchangeable biosimilar by
the FDA, it can be used to replace the reference product by someone other than
the prescriber (such as a pharmacist), without the need to consult the
prescriber, depending on the state pharmacy laws.2 This is similar
to how generic drugs are commonly substituted for brand name drugs.

About HADLIMA™ (adalimumab-bwwd) Injection 40 mg/0.4 mL and 40 mg/0.8

HADLIMA is a tumor necrosis factor (TNF) blocker indicated for:

  • Rheumatoid Arthritis: HADLIMA is indicated, alone or in
    combination with methotrexate or other non-biologic disease-modifying
    antirheumatic drugs (DMARDs), for reducing signs and symptoms, inducing
    major clinical response, inhibiting the progression of structural damage,
    and improving physical function in adult patients with moderately to
    severely active rheumatoid arthritis.
  • Juvenile Idiopathic Arthritis: HADLIMA is indicated, alone
    or in combination with methotrexate, for reducing signs and symptoms of
    moderately to severely active polyarticular juvenile idiopathic arthritis in
    patients 2 years of age and older.
  • Psoriatic Arthritis: HADLIMA is indicated, alone or in
    combination with non-biologic DMARDs, for reducing signs and symptoms,
    inhibiting the progression of structural damage, and improving physical
    function in adult patients with active psoriatic arthritis.
  • Ankylosing Spondylitis: HADLIMA is indicated for reducing
    signs and symptoms in adult patients with active ankylosing spondylitis.
  • Crohn’s Disease: HADLIMA is indicated for the
    treatment of moderately to severely active Crohn’s disease in adults
    and pediatric patients 6 years of age and older.
  • Ulcerative Colitis: HADLIMA is indicated for the treatment
    of moderately to severely active ulcerative colitis in adult patients.

    Limitations of Use:
    The effectiveness of adalimumab products
    has not been established in patients who have lost response to or were intolerant
    to tumor necrosis factor (TNF) blockers.

  • Plaque Psoriasis: HADLIMA is indicated for the treatment of
    adult patients with moderate to severe chronic plaque psoriasis who are
    candidates for systemic therapy or phototherapy, and when other systemic
    therapies are medically less appropriate. HADLIMA should only be
    administered to patients who will be closely monitored and have regular
    follow-up visits with a physician.
  • Hidradenitis Suppurativa: HADLIMA is indicated for the
    treatment of moderate to severe hidradenitis suppurativa in adult patients.
  • Uveitis: HADLIMA is indicated for the treatment of
    non-infectious intermediate, posterior, and panuveitis in adult patients.



Patients treated with adalimumab products, including HADLIMA, are at
increased risk for developing serious infections that may lead to
hospitalization or death. Most patients who developed these infections were
taking concomitant immunosuppressants such as methotrexate or

Discontinue HADLIMA if a patient develops a serious infection or

Reported infections include:

  • Active tuberculosis (TB), including reactivation of latent TB. Patients
    with TB have frequently presented with disseminated or extrapulmonary
    disease. Test patients for latent TB before HADLIMA use and during
    therapy. Initiate treatment for latent TB prior to HADLIMA use.
  • Invasive fungal infections, including histoplasmosis, coccidioidomycosis,
    candidiasis, aspergillosis, blastomycosis, and pneumocystosis. Patients
    with histoplasmosis or other invasive fungal infections may present with
    disseminated, rather than localized, disease. Antigen and antibody testing
    for histoplasmosis may be negative in some patients with active infection.
    Consider empiric anti-fungal therapy in patients at risk for invasive
    fungal infections who develop severe systemic illness.
  • Bacterial, viral, and other infections due to opportunistic pathogens,
    including Legionella and Listeria.

Carefully consider the risks and benefits of treatment with HADLIMA prior
to initiating therapy in patients:

  • with chronic or recurrent infection
  • who have been exposed to TB
  • with a history of opportunistic infection
  • who resided in or traveled in regions where mycoses are endemic
  • with underlying conditions that may predispose them to infection

Monitor patients closely for the development of signs and symptoms of
infection during and after treatment with HADLIMA, including the possible
development of TB in patients who tested negative for latent TB infection
prior to initiating therapy.

  • Do not start HADLIMA during an active infection, including localized
  • Patients older than 65 years, patients with co-morbid conditions, and/or
    patients taking concomitant immunosuppressants may be at greater risk of
  • If an infection develops, monitor carefully and initiate appropriate
  • Drug interactions with biologic products: A higher rate of serious
    infections has been observed in rheumatoid arthritis (RA) patients treated
    with rituximab who received subsequent treatment with a TNF blocker. An
    increased risk of serious infections has been seen with the combination of
    TNF blockers with anakinra or abatacept, with no demonstrated added benefit
    in patients with RA. Concomitant administration of HADLIMA with other
    biologic DMARDs (eg, anakinra or abatacept) or other TNF blockers is not
    recommended based on the possible increased risk for infections and other
    potential pharmacological interactions.


Lymphoma and other malignancies, some fatal, have been reported in children
and adolescent patients treated with TNF blockers, including adalimumab
products. Postmarketing cases of hepatosplenic T-cell lymphoma (HSTCL), a
rare type of T-cell lymphoma, have been reported in patients treated with
TNF blockers, including adalimumab products. These cases have had a very
aggressive disease course and have been fatal. The majority of reported TNF
blocker cases have occurred in patients with Crohn’s disease or
ulcerative colitis and the majority were in adolescent and young adult
males. Almost all of these patients had received treatment with azathioprine
or 6-mercaptopurine concomitantly with a TNF blocker at or prior to
diagnosis. It is uncertain whether the occurrence of HSTCL is related to use
of a TNF blocker or a TNF blocker in combination with these other

  • Consider the risks and benefits of HADLIMA treatment prior to initiating or
    continuing therapy in a patient with known malignancy.
  • In clinical trials, more cases of malignancies were observed among
    adalimumab-treated patients compared to control patients.
  • Non-melanoma skin cancer (NMSC) was reported during clinical trials for
    adalimumab-treated patients. Examine all patients, particularly those with a
    history of prolonged immunosuppressant or psoralen and ultraviolet A (PUVA)
    therapy, for the presence of NMSC prior to and during treatment with
  • In adalimumab clinical trials, there was an approximate 3-fold higher rate
    of lymphoma than expected in the general U.S. population. Patients with
    chronic inflammatory diseases, particularly those with highly active disease
    and/or chronic exposure to immunosuppressant therapies, may be at higher
    risk of lymphoma than the general population, even in the absence of TNF
  • Postmarketing cases of acute and chronic leukemia were reported with TNF
    blocker use. Approximately half of the postmarketing cases of malignancies
    in children, adolescents, and young adults receiving TNF blockers were
    lymphomas; other cases included rare malignancies associated with
    immunosuppression and malignancies not usually observed in children and


Anaphylaxis and angioneurotic edema have been reported following adalimumab
administration. If a serious allergic reaction occurs, stop HADLIMA and
institute appropriate therapy.


Use of TNF blockers, including HADLIMA, may increase the risk of reactivation
of hepatitis B virus (HBV) in patients who are chronic carriers. Some cases
have been fatal.

Evaluate patients at risk for HBV infection for prior evidence of HBV
infection before initiating TNF blocker therapy.

Exercise caution in patients who are carriers of HBV and monitor them during
and after HADLIMA treatment.

Discontinue HADLIMA and begin antiviral therapy in patients who develop HBV

Exercise caution when resuming HADLIMA after HBV treatment.


TNF blockers, including adalimumab products, have been associated with rare
cases of new onset or exacerbation of central nervous system and peripheral
demyelinating diseases, including multiple sclerosis, optic neuritis, and
Guillain-Barré syndrome.

Exercise caution when considering HADLIMA for patients with these disorders;
discontinuation of HADLIMA should be considered if any of these disorders


Rare reports of pancytopenia, including aplastic anemia, have been reported
with TNF blockers. Medically significant cytopenia has been infrequently
reported with adalimumab products.

Consider stopping HADLIMA if significant hematologic abnormalities occur.


Worsening and new onset congestive heart failure (CHF) has been reported with
TNF blockers. Cases of worsening CHF have been observed with adalimumab
products; exercise caution and monitor carefully.


Treatment with adalimumab products may result in the formation of
autoantibodies and, rarely, in development of a lupus-like syndrome.
Discontinue treatment if symptoms of a lupus-like syndrome develop.


Patients on HADLIMA should not receive live vaccines.

Pediatric patients, if possible, should be brought up to date with all
immunizations before initiating HADLIMA therapy.

Adalimumab is actively transferred across the placenta during the third
trimester of pregnancy and may affect immune response in the in utero-exposed infant. The safety of administering live or live-attenuated vaccines
in infants exposed to adalimumab products in utero is
unknown. Risks and benefits should be considered prior to vaccinating (live or
live-attenuated) exposed infants.


The most common adverse reactions in adalimumab clinical trials (>10%)
were: infections (eg, upper respiratory, sinusitis), injection site reactions,
headache, and rash.

Before prescribing HADLIMA, please read the Prescribing Information, including the Boxed Warning about serious infections and malignancies.
Medication Guide and Instructions for Use also are available.

About Samsung Bioepis Co., Ltd.

Established in 2012, Samsung Bioepis is a biopharmaceutical company committed
to realizing health care that is accessible to everyone. Through innovations
in product development and a firm commitment to quality, Samsung Bioepis aims
to become the world’s leading biopharmaceutical company. Samsung Bioepis
continues to advance a broad pipeline of biosimilar candidates that cover a
spectrum of therapeutic areas, including immunology, oncology, ophthalmology,
hematology, and endocrinology. For more information, please visit: and follow us on social media – Twitter, LinkedIn.

About Organon

Organon is a global health care company formed to focus on improving the
health of women throughout their lives. Organon offers more than 60 medicines
and products in women’s health in addition to a growing biosimilars
business and a large franchise of established medicines across a range of
therapeutic areas. Organon’s existing products produce strong cash flows
that support investments in innovation and future growth opportunities in
women’s health and biosimilars. In addition, Organon is pursuing
opportunities to collaborate with biopharmaceutical innovators looking to
commercialize their products by leveraging its scale and presence in fast
growing international markets. Organon has a global footprint with significant
scale and geographic reach, world-class commercial capabilities, and
approximately 10,000 employees with headquarters located in Jersey City, New

For more information, visit and connect with
us on LinkedIn and

About the Samsung Bioepis-Organon Collaboration
is developed, manufactured and supplied by Samsung Bioepis, and commercialized
by Organon. Samsung Bioepis and Organon have development and commercialization
collaborations for two immunology products and one oncology product in the
United States.

ORGANON, the Organon Logo, and HADLIMA are trademarks of N.V. Organon. All
other trademarks appearing herein are trademarks of their respective owners.

Cautionary Note Regarding Forward-Looking Statements

Some statements and disclosures in this press release are
“forward-looking statements” within the meaning of the safe harbor
provisions of the U.S. Private Securities Litigation Reform Act of 1995.
Forward-looking statements include all statements that do not relate solely to
historical or current facts and can be identified by the use of words such as
“may,” “expects,” “intends,”
“anticipates,” “plans,” “believes,”
“seeks,” “estimates,” “will,” or words of
similar meaning. These forward-looking statements are based on Organon’s
current plans and expectations and are subject to a number of risks and
uncertainties that could cause Organon’s plans and expectations,
including actual results, to differ materially from the forward-looking

Risks and uncertainties that may affect Organon’s future results
include, but are not limited to, an inability to fully execute on the product
development and commercialization plans for HADLIMA in the United States due
to Organon’s inability to realize the benefits of its SB5 HADLIMA
biosimilar; efficacy, safety, or other quality concerns with respect to
marketed products, including market actions such as recalls, withdrawals, or
declining sales; political and social pressures, or regulatory developments,
that adversely impact demand for, availability of, or patient access to
Organon’s products; general economic factors, including recessionary
pressures, interest rate and currency exchange rate fluctuations; general
industry conditions and competition; the impact of the ongoing COVID-19
pandemic and emergence of variant strains; the impact of pharmaceutical
industry regulation and health care legislation in the United States and
internationally; global trends toward health care cost containment;
technological advances; new products and patents attained by competitors;
challenges inherent in new product development, including obtaining regulatory
approval; global tensions, which may result in disruptions in the broader
global economy; uncertainty regarding the U.S. federal budget and debt
ceiling, and the impact of a potential U.S. federal government shutdown;
governmental initiatives that adversely impact our marketing activities,
particularly in China; Organon’s ability to accurately predict its
future financial results and performance; manufacturing difficulties or
delays; financial instability of international economies and sovereign risk;
difficulties developing and sustaining relationships with commercial
counterparties; dependence on the effectiveness of Organon’s patents and
other protections for innovative products; and the exposure to litigation,
including patent litigation, and/or regulatory actions.

Organon undertakes no obligation to publicly update any forward-looking
statement, whether as a result of new information, future events or otherwise.
Additional factors that could cause results to differ materially from those
described in the forward-looking statements can be found in Organon’s
filings with the Securities and Exchange Commission (“SEC”), including
Organon’s Annual Report on Form 10-K for the year ended
December 31, 2022, and subsequent SEC filings, available at the
SEC’s Internet site (

Media Contacts – Samsung Bioepis

Anna Nayun Kim,

Jane Chung,

Media Contacts – Organon

Kim Burke Hamilton,

Karissa Peer,

1. Samsung Bioepis & Organon press release. Samsung Bioepis & Organon
Announce Topline Results from Interchangeability Study of SB5 Humira
Biosimilar. Issued on August 1, 2023.

2. The U.S. Food and Drug Administration. Biosimilar and Interchangeable
Biologics: More Treatment Choices.
Accessed September 2023

3. The U.S. Food and Drug Administration. Considerations in Demonstrating
Interchangeability With a Reference Product Guidance for Industry. Accessed September 2023