Samsung Bioepis and Organon Announce FDA Approval of Citrate-Free High-Concentration HUMIRA® Biosimilar HADLIMA™ (adalimumab-bwwd)

INCHEON, Korea & JERSEY CITY, N.J.--(BUSINESS WIRE)--Samsung Bioepis Co., Ltd. and Organon & Co. (NYSE: OGN) today announced the U.S. Food and Drug Administration (FDA) has approved the citrate-free, high-concentration (100 mg/mL) formulation of HADLIMA™ (adalimumab-bwwd), a biosimilar referencing HUMIRA^® (adalimumab). HADLIMA will be available in pre-filled syringe and autoinjector options, and the autoinjector was specifically designed with the patient in mind. HADLIMA was previously approved by the FDA as a low-concentration (50 mg/mL) formulation in July 2019 and outside the US that formulation has been available in various markets globally under different brand names, with over 5 million doses sold since 2018.^1,2

“With this approval, we now have both a low and high concentration adalimumab biosimilar approved by the FDA, marking an important step towards expanding treatment options for patients suffering from certain chronic, autoimmune diseases,” said Byoungin Jung, Vice President and Regulatory Affairs Team Leader, Samsung Bioepis. “By leveraging our development expertise, manufacturing excellence and supply chain reliability, we will continue our work to ensure healthcare systems have more affordable treatment options available,” she added.

“Based on our success commercializing our adalimumab biosimilar in other markets around the world, combined with our established presence in the biosimilar space, we are excited about the opportunity to launch HADLIMA in the US in 2023,” said Joe Azzinaro, Vice President, Global Commercial Lead Biosimilars, Organon. “Today, adalimumab is the largest drug expense in the US. We look forward to making our biosimilar available for those that rely on it to help manage their disease.”

The approval of citrate-free, high-concentration HADLIMA was based on clinical data from a randomized, single-blind, two-arm, parallel group, single-dose study that compared the pharmacokinetics, safety, tolerability, and immunogenicity of two formulations of HADLIMA (100 mg/mL vs 50 mg/mL) in healthy volunteers.³

HADLIMA is expected to be launched on or after July 1, 2023 by Organon.

About Biosimilars

A biosimilar is a biologic product that is highly similar to and has no clinically meaningful differences from an existing FDA-approved reference product.⁴ Biologics are the fastest-growing class of therapeutic products in the U.S., and biosimilars can increase competition in the marketplace, potentially lowering health care costs.⁴ Wider use of biosimilars could result in savings of $100 billion in the U.S. between 2020 to 2024 by stimulating market competition.⁵

About HADLIMA™ (adalimumab-bwwd)

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 anti-rheumatic 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 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.

Selected Safety Information

SERIOUS INFECTIONS

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 corticosteroids.

Discontinue HADLIMA if a patient develops a serious infection or sepsis.

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.

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.

Treatment with HADLIMA should not be initiated in patients with an active infection, including localized infections. Patients 65 years of age and older, patients with co-morbid conditions and/or patients taking concomitant immunosuppressants (such as corticosteroids or methotrexate), may be at greater risk of infection. Consider the risks and benefits of treatment prior to initiating therapy in patients:

• with chronic or recurrent infection;
• who have been exposed to tuberculosis;
• with a history of an opportunistic infection;
• who have resided or traveled in areas of endemic tuberculosis or endemic mycoses, such as histoplasmosis, coccidioidomycosis, or blastomycosis; or
• with underlying conditions that may predispose them to infection.

Discontinue HADLIMA if a patient develops a serious infection or sepsis. For a patient who develops a new infection during treatment with HADLIMA, closely monitor them, perform a prompt and complete diagnostic workup appropriate for an immunocompromised patient, and initiate appropriate antimicrobial therapy.

Drug interactions with biologic products: In clinical studies in patients with RA, an increased risk of serious infections has been observed with the combination of TNF blockers with anakinra or abatacept, with no added benefit; therefore, use of HADLIMA with abatacept or anakinra is not recommended in patients with RA. A higher rate of serious infections has also been observed in patients with RA treated with rituximab who received subsequent treatment with a TNF blocker. There is insufficient information regarding the concomitant use of HADLIMA and other biologic products for the treatment of RA, PsA, AS, CD, UC and Ps. Concomitant administration of HADLIMA with other biologic DMARDs (e.g., anakinra and abatacept) or other TNF blockers is not recommended based upon the possible increased risk for infections and other potential pharmacological interactions.

MALIGNANCY

Lymphoma and other malignancies, some fatal, have been reported in children and adolescent patients treated with TNF blockers including adalimumab products. Post-marketing 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 immunosuppressants.

• Consider the risks and benefits of TNF-blocker treatment including HADLIMA prior to initiating therapy in patients with a known malignancy other than a successfully treated non-melanoma skin cancer (NMSC) or when considering continuing a TNF blocker in patients who develop a malignancy.
• In the controlled portions of clinical trials of some TNF-blockers, including adalimumab products, more cases of malignancies have been observed among TNF-blocker-treated adult patients compared to control-treated adult patients.
• Non-melanoma skin cancer (NMSC) was reported during clinical trials for adalimumab-treated patients. Examine all patients, and in particular patients with a medical history of prior prolonged immunosuppressant therapy or psoriasis patients with a history of PUVA treatment for the presence of NMSC prior to and during treatment with HADLIMA.
• In the controlled portions of clinical trials of all the TNF-blockers in adults, more cases of lymphoma have been observed among TNF-blocker-treated patients compared to control-treated patients. There was approximately a 3-fold higher than expected rate in the general U.S. population. Patients with RA and other chronic inflammatory diseases, particularly those with highly active disease and/or chronic exposure to immunosuppressant therapies, may be at a higher risk than the general population for the development of lymphoma, even in the absence of TNF blockers.
• Post-marketing cases of acute and chronic leukemia were reported with TNF blocker use in RA and other indications.
• Malignancies, some fatal, have been reported among children, adolescents, and young adults who received treatment with TNF-blockers (initiation of therapy ≤ 18 years of age), of which HADLIMA is a member. Approximately half the cases were lymphomas, including Hodgkin's and non-Hodgkin's lymphoma. The other cases represented a variety of different malignancies and included rare malignancies usually associated with immunosuppression and malignancies that are not usually observed in children and adolescents.

HYPERSENSITIVITY REACTIONS

• Anaphylaxis and angioneurotic edema have been reported following administration of adalimumab products. If an anaphylactic or other serious allergic reaction occurs, immediately discontinue administration of HADLIMA and institute appropriate therapy. In clinical trials of adalimumab, hypersensitivity reactions (e.g., rash, anaphylactoid reaction, fixed drug reaction, non-specified drug reaction, urticaria) have been observed.

HEPATITIS B VIRUS REACTIVATION

• Use of TNF blockers, including HADLIMA, may increase the risk of reactivation of hepatitis B virus (HBV) in patients who are chronic carriers. In some instances, HBV reactivation occurring in conjunction with TNF blocker therapy has been fatal.
• Evaluate patients at risk for HBV infection for prior evidence of HBV infection before initiating TNF blocker therapy.
• Exercise caution in prescribing TNF blockers for patients identified as carriers of HBV and monitor them during and after HADLIMA treatment. Adequate data are not available on the safety or efficacy of treating patients who are carriers of HBV with anti-viral therapy in conjunction with TNF blocker therapy to prevent HBV reactivation.
• In patients who develop HBV reactivation, stop HADLIMA and initiate effective anti-viral therapy with appropriate supportive treatment. The safety of resuming TNF blocker therapy after HBV reactivation is controlled is not known. Therefore, exercise caution when considering resumption of HADLIMA therapy in this situation and monitor patients closely.

NEUROLOGIC REACTIONS

• Use of TNF blocking agents, including adalimumab products, has been associated with rare cases of new onset or exacerbation of clinical symptoms and/or radiographic evidence of central nervous system demyelinating disease, including multiple sclerosis and optic neuritis, and peripheral demyelinating disease, including Guillain-Barré syndrome.
• Exercise caution in considering the use of HADLIMA in patients with preexisting or recent-onset central or peripheral nervous system demyelinating disorders; discontinuation of HADLIMA should be considered if any of these disorders develop.

HEMATOLOGICAL REACTIONS

• Rare reports of pancytopenia including aplastic anemia have been reported with TNF blocking agents. Medically significant cytopenia has been infrequently reported with HADLIMA.
• Adverse reactions of the hematologic system, including medically significant cytopenia (e.g., thrombocytopenia, leukopenia) have been infrequently reported with adalimumab products. The causal relationship of these reports to adalimumab products remains unclear. Advise all patients to seek immediate medical attention if they develop signs and symptoms suggestive of blood dyscrasias or infection (e.g., persistent fever, bruising, bleeding, pallor) while on HADLIMA.
• Consider discontinuation of HADLIMA therapy in patients with confirmed significant hematologic abnormalities.

INCREASED RISK OF INFECTION WHEN USED WITH ANAKINRA

• Concurrent use of anakinra (an interleukin-1 antagonist) and another TNF-blocker, was associated with a greater proportion of serious infections and neutropenia and no added benefit compared with the TNF blocker alone in patients with RA. Therefore, the combination of HADLIMA and anakinra is not recommended.

HEART FAILURE

• Cases of worsening congestive heart failure (CHF) and new onset CHF have been reported with TNF blockers. Cases of worsening CHF have also been observed with adalimumab products. Adalimumab products have not been formally studied in patients with CHF; however, in clinical trials of another TNF blocker, a higher rate of serious CHF-related adverse reactions was observed. Exercise caution and monitor carefully.

AUTOIMMUNITY

• Treatment with adalimumab products may result in the formation of autoantibodies and, rarely, in the development of a lupus-like syndrome. If a patient develops symptoms suggestive of a lupus-like syndrome following treatment with HADLIMA, discontinue treatment.

IMMUNIZATIONS

• Patients on HADLIMA may receive concurrent vaccinations, except for live vaccines. No data are available on the secondary transmission of infection by live vaccines in patients receiving adalimumab products.
• It is recommended that pediatric patients, if possible, be brought up to date with all immunizations in agreement with current immunization guidelines prior to initiating HADLIMA therapy. Patients on HADLIMA may receive concurrent vaccinations, except for live vaccines.
• 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.

ADVERSE REACTIONS

The most common adverse reactions in HADLIMA clinical trials (>10%) were: infections (e.g., upper respiratory, sinusitis), injection site reactions, headaches, and rash.

Before prescribing HADLIMA, please read the accompanying Prescribing Information, including the Boxed Warning about serious infections and malignancies. The Medication Guide is also available.

About Samsung Bioepis Co., Ltd.

Established in 2012, Samsung Bioepis is a biopharmaceutical company committed to realizing healthcare 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, endocrinology, and gastroenterology. For more information, please visit: www.samsungbioepis.com and follow us on social media – Twitter, LinkedIn.

About Organon

Organon is a global healthcare company formed to focus on improving the health of women throughout their lives. Organon has a portfolio of more than 60 medicines and products across a range of therapeutic areas. Led by the women’s health portfolio coupled with an expanding biosimilars business and stable franchise of established medicines, Organon’s products produce strong cash flows that will support investments in innovation and future growth opportunities. 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 9,300 employees with headquarters located in Jersey City, New Jersey.

For more information, visit http://www.organon.com and connect with us on LinkedIn and Instagram.

Forward-Looking Statements

Except for historical information herein, this news release includes “forward-looking statements” within the meaning of the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995, including, but not limited to, statements about Organon management’s expectations about Organon’s launch and commercialization of HADLIMA and its collaboration with Samsung Bioepis. Forward-looking statements may be identified by words such as “expects,” “intends,” “anticipates,” “plans,” “believes,” “seeks,” “estimates,” “will” or words of similar meaning. These statements are based upon the current beliefs and expectations of Organon‘s management and are subject to significant risks and uncertainties. If underlying assumptions prove inaccurate or risks or uncertainties materialize, actual results may differ materially from those set forth in the forward-looking statements.

Risks and uncertainties include, but are not limited to, an inability to execute on our business development strategy or realize the benefits of our planned acquisitions; general economic factors, including 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; Organon’s ability to accurately predict its future financial results and performance; Organon‘s ability to accurately predict future market conditions; 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, 2021 and subsequent SEC filings, available at the SEC’s Internet site (www.sec.gov).

References and links to websites have been provided for convenience, and the information contained on any such website is not a part of, or incorporated by reference into, this press release. Organon is not responsible for the contents of third-party websites.

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¹ HADLIMA Label. August 16, 2022. Available at https://www.organon.com/wp-content/uploads/sites/2/2022/08/FDA_b761059_S005_Hadlima_8.15.22_letterlabeling_002_clean.pdf
² IQVIA MIDAS data. Worldwide sales of SB5, Samsung Bioepis's adalimumab biosimilar. As of March 2022
³ Ahn SS, Lee M, Baek Y, Lee S. A randomized phase I pharmacokinetic study comparing high-concentration, low-volume, and citrate-free SB5 (40 mg/0.4 mL) with prior SB5 formulation, and adalimumab biosimilar, in healthy male subjects. Presented at: EULAR 2022; June 1-4, 2022; Copenhagen, Denmark. Abstract POS0641.
⁴ U.S. Food and Drug Administration. Biosimilar and Interchangeable Products. Available at: https://www.fda.gov/drugs/biosimilars/biosimilar-and-interchangeable-products. Accessed August 2022.
⁵ IQVIA Institute for Human Data Science. (October 2020). “Biosimilars in the United States 2020–2024.” https://www.iqvia.com/insights/the-iqvia-institute/reports/biosimilars-in-the-united-states-2020-2024. Accessed August 2022