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

INCHEON, Korea and Jersey City, N.J., United States – August 17, 2022 – 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.

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

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 adults and pediatric patients 5 years of age and older.

Limitations of Use: The effectiveness of Hadlima 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.

• Do not start Hadlima during an active infection, including localized infections.

• Patients older than 65 years, patients with co-morbid conditions, and/or patients taking concomitant immunosuppressants may be at greater risk of infection.

• If an infection develops, monitor carefully and initiate appropriate therapy.

• Drug interactions with biologic products: A higher rate of serious infections has been observed in 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 (e.g., anakinra or abatacept) or other TNF blockers is not recommended based on the possible increased risk for infections and other potential pharmacological interactions.

• 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 Hadlima-treated patients compared to control patients.

• Non-melanoma skin cancer (NMSC) was reported during clinical trials for Hadlima-treated patients. Examine all patients, particularly those with a history of prolonged immunosuppressant or PUVA therapy, for the presence of NMSC prior to and during treatment with Hadlima.

• In Hadlima 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 blockers.

• 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 adolescents.

• Anaphylaxis and angioneurotic edema have been reported following Hadlima 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 reactivation. Exercise caution when resuming Hadlima after HBV treatment.

• TNF blockers, including Hadlima, 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 develop.

• There is a known association between intermediate uveitis and central demyelinating disorders.

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

• 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 Hadlima; exercise caution and monitor carefully.

• Treatment with Hadlima 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 Hadlima 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 Hadlima clinical trials (>10%) were: infections (e.g., upper respiratory, sinusitis), injection site reactions, headache, and rash.

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.

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.

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.

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 health 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