Samsung Bioepis Announces First Real-World Data on RENFLEXIS® (infliximab-abda) with IBD patients from Veterans Affairs Healthcare System at the American College of Gastroenterology (ACG) 2020

• Switching fromreference infliximab or infliximab-dyyb to RENFLEXIS^® (infliximab-abda)demonstrated comparable efficacy and safetyin IBD patients registered to VA Healthcare System
• Continuation rates were similar for patients who underwent a single switch from reference infliximab to RENFLEXIS^®or double switch from reference infliximab to infliximab-dyybto RENFLEXIS^®
• RENFLEXIS^® listed on VA National Formulary sinceSeptember 2018

INCHEON, Korea, Oct. 26, 2020 (GLOBE NEWSWIRE) -- Samsung Bioepis Co., Ltd. today announced results from two real-world studies of RENFLEXIS^® (infliximab-abda) in patients with Inflammatory Bowel Disease (IBD) registered in the U.S. Veteran Affairs Healthcare System database. The data were presented for the first time at the American College of Gastroenterology (ACG) 2020 Annual Scientific Meeting, which is held virtually from October 23-28, 2020.

One nationwide study evaluated the safety of switching from reference infliximab or infliximab-dyyb to RENFLEXIS^® (infliximab-abda) in patients with IBD identified from the VAHS database. Among 298 patients who were switched to RENFLEXIS^®, continuation rate was 83% over one year. The study also found that continuation rates were similar between patients who underwent a single switch from reference infliximab to RENFLEXIS^® or double switch from reference infliximab to infliximab-dyyb to RENFLEXIS^®, reflecting the safety of switching from either reference product or biosimilar.

Nabeel Khan, MD, Associate Professor of Clinical Medicine, University of Pennsylvania, who led the study said, “since IBD symptoms can be severe, maintaining a stable condition is important for IBD management. This study demonstrated that patients who were on infliximab, reference product or biosimilar, can remain stable after switching to another biosimilar, without major safety concerns.”

Another study looked at real-world utilization pattern of infliximab products for IBD, within the context of Veterans Affairs National Formulary (VANF) Policy. It found that adoption of RENFLEXIS^®, which became the preferred infliximab product on VANF in September 2018, was faster than adoption of the previous biosimilar (infliximab-dyyb) that was listed on VANF in May 2017.

“We are confident that this real-world switch data will provide additional reassurance to gastroenterologists who are treating patients with IBD,” said Seongwon Han, Vice President, Medical & Lifecycle Safety Team Leader, at Samsung Bioepis. He continued “together with our partners, we remain committed to demonstrating the value of biosimilars for patients and physicians, as well as payers.”

Both studies are presented as ePosters, which are available on the ACG 2020 Virtual Meeting Platform.

RENFLEXIS^® (infliximab-abda) was approved by the U.S. Food and Drug Administration in April 2017 as a biosimilar to REMICADE^®1 (infliximab). In the United States, RENFLEXIS^® is commercialized by Merck, also known as MSD outside of the U.S. and Canada. In September 2018, it was awarded a national contract from U.S. Department of Veterans Affairs (VA), and is currently the only infliximab option listed on the VA National Formulary (VANF). RENFLEXIS^® is currently listed at USD 121.43 (National Contract Price)² on VANF and is expected to bring cost savings of approximately USD 81 million every year for the Veteran Affairs Healthcare System from 2018 to 2023, if widely adopted.³

About two real-world studies of RENFLEXIS^® (infliximab-abda) in IBD patients

Abstract P1597: The safety of switching from originator infliximab or CT-P13 to SB2 among a nationwide cohort of Inflammatory Bowel Disease patients. Nabeel Khan et al.

For the nationwide retrospective cohort study, a total of 298 patients registered to the VA Informatics and Computing Infrastructure (VINCI) from Jan 1, 2017 to May 1, 2020 were followed-up for one year after starting treatment with infliximab-abda. Patients who were treated with reference infliximab and/or infliximab-dyyb and maintained stable IBD conditions¹ for three months before switching were eligible for the study. The primary outcome observed was the discontinuation rate at one-year, which was 17%. Continuation rates were similar between patients who switched one time (reference infliximab → infliximab-abda) and two times (reference infliximab → infliximab-dyyb → infliximab-abda), at 87% and 82% respectively. 13% of the total patients stopped due to either loss of response, development of antibodies, or a hypersensitivity reaction.

Abstract P1570:Infliximab Biosimilar use for Inflammatory Bowel Disease: A National Veterans Affairs Experience. Jessica Johnson et al.

The purpose of the second study was to describe infliximab product selection for Crohn’s Disease (CD) and Ulcerative Colitis (UC) during the time frame when biosimilars entered the VA and obtained VANF status. Infliximab products were used in 3,204 Veterans with IBD (60.2% CD, 39.8% UC). Non-formulary use of infliximab occurred in higher percentage of infliximab experienced patients than infliximab-naïve patients. Product selection changed throughout the years, reflecting VANF status: Infliximab was used with the highest frequency in 2016-2017, infliximab-dyyb during 2018, and infliximab-abda during 2019. The time delay between the initial designation as the preferred infliximab product and becoming the most frequently used infliximab product in infliximab-naïve Veterans was five months for infliximab-dyyb and two months for infliximab-abda.

Indications for RENFLEXIS (infliximab-abda) for Injection, for intravenous use 100 mg

RENFLEXIS is a tumor necrosis factor (TNF) blocker approved in the U.S. for the following indications.

Crohn’s Disease – RENFLEXIS is indicated for reducing signs and symptoms and inducing and maintaining clinical remission in adult patients with moderately to severely active Crohn’s disease (CD) who have had an inadequate response to conventional therapy. RENFLEXIS is indicated for reducing the number of draining enterocutaneous and rectovaginal fistulas and maintaining fistula closure in adult patients with fistulizing Crohn’s disease.

Pediatric Crohn’s Disease – RENFLEXIS is indicated for reducing signs and symptoms and inducing and maintaining clinical remission in pediatric patients 6 years of age or older with moderately to severely active Crohn’s disease (CD) who have had an inadequate response to conventional therapy

Ulcerative Colitis – RENFLEXIS is indicated for reducing signs and symptoms, inducing and maintaining clinical remission and mucosal healing, and eliminating corticosteroid use in adult patients with moderately to severely active ulcerative colitis (UC) who have had an inadequate response to conventional therapy.

Pediatric Ulcerative Colitis -- RENFLEXIS is indicated for reducing signs and symptoms and inducing and maintaining clinical remission in pediatric patients 6 years of age and older with moderately to severely active ulcerative colitis (UC) who have had an inadequate response to conventional therapy

Rheumatoid Arthritis – RENFLEXIS is indicated for reducing signs and symptoms, inhibiting the progression of structural damage, and improving physical function in patients with moderately to severely active rheumatoid arthritis (RA) in combination with methotrexate (MTX).

Psoriatic Arthritis – RENFLEXIS is indicated for reducing signs and symptoms of active arthritis, inhibiting the progression of structural damage, and improving physical function in patients with psoriatic arthritis (PsA).

Ankylosing Spondylitis – RENFLEXIS is indicated for reducing signs and symptoms in patients with active ankylosing spondylitis (AS).

Plaque Psoriasis – RENFLEXIS is indicated for the treatment of adult patients with chronic severe (i.e., extensive and/or disabling) plaque psoriasis who are candidates for systemic therapy and when other systemic therapies are medically less appropriate. RENFLEXIS should only be administered to patients who will be closely monitored and have regular follow-up visits with a physician.

Selected Safety Information about RENFLEXIS (infliximab-abda)

SERIOUS INFECTIONS

Patients treated with infliximab products 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 RENFLEXIS if a patient develops a serious infection or sepsis.

Reported infections include:

• Active tuberculosis (TB), including reactivation of latent TB. Patients frequently presented with disseminated or extrapulmonary disease. Patients should be tested for latent TB before RENFLEXIS (infliximab-abda) use and during therapy.^1,2 Treatment for latent infection should be initiated prior to RENFLEXIS use.
• Invasive fungal infections, including histoplasmosis, coccidioidomycosis, candidiasis, aspergillosis, blastomycosis,pneumocystosis, andcryptococcosis. Patients may present with disseminated, rather than localized, disease. Antigen and antibody testing for histoplasmosis may be negative in some patients with active infection. Empiric anti-fungal therapy should be considered 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.

The risks and benefits of treatment with RENFLEXIS should be carefully considered prior to initiating therapy in patients with chronic or recurrent infection. Closely monitor patients for the development of signs and symptoms of infection during and after treatment with RENFLEXIS, including the possible development of TB in patients who tested negative for latent TB infection prior to initiating therapy, who are on treatment for latent TB, or who were previously treated for TB infection.

Risk of infection may be higher in patients greater than 65 years of age, pediatric patients, patients with comorbid conditions and/or patients taking concomitant immunosuppressant therapy. In clinical trials, other serious infections observed in patients treated with infliximab products included pneumonia, cellulitis, abscess, and skin ulceration.

MALIGNANCIES

Lymphoma and other malignancies, some fatal, have been reported in children and adolescent patients treated with tumor necrosis factor (TNF) blockers, including infliximab products. Approximately half of these cases were lymphomas, including Hodgkin’s and non-Hodgkin’s lymphoma. The other cases represented a variety of malignancies, including rare malignancies that are usually associated with immunosuppression and malignancies that are not usually observed in children and adolescents. The malignancies occurred after a median of 30 months after the first dose of therapy. Most of the patients were receiving concomitant immunosuppressants.

Postmarketing cases of hepatosplenic T-cell lymphoma, a rare type of T-cell lymphoma, have been reported in patients treated with TNF blockers, including infliximab products. These cases have had a very aggressive disease course and have been fatal. The majority of reported cases have occurred in patients with Crohn’s disease or ulcerative colitis and most 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. Carefully assess the risks and benefits of treatment with RENFLEXIS (infliximab-abda), especially in these patient types.

In clinical trials of all TNF inhibitors, more cases of lymphoma were observed compared with controls and the expected rate in the general population. However, patients with Crohn’s disease, rheumatoid arthritis, or plaque psoriasis may be at higher risk for developing lymphoma. In clinical trials of some TNF inhibitors, including infliximab products, more cases of other malignancies were observed compared with controls. The rate of these malignancies among patients treated with infliximab products was similar to that expected in the general population whereas the rate in control patients was lower than expected. Cases of acute and chronic leukemia have been reported with postmarketing TNF-blocker use. As the potential role of TNF inhibitors in the development of malignancies is not known, caution should be exercised when considering treatment of patients with a current or a past history of malignancy or other risk factors such as chronic obstructive pulmonary disease (COPD).

Melanoma and Merkel cell carcinoma have been reported in patients treated with TNF-blocker therapy, including infliximab products. Periodic skin examination is recommended for all patients, particularly those with risk factors for skin cancer.

A population-based retrospective cohort study found a 2- to 3-fold increase in the incidence of invasive cervical cancer in women with rheumatoid arthritis treated with infliximab compared to biologics-naïve patients or the general population, particularly those over 60 years of age. A causal relationship between infliximab products and cervical cancer cannot be excluded. Periodic screening should continue in women treated with infliximab products.

CONTRAINDICATIONS

RENFLEXIS (infliximab-abda) is contraindicated in patients with moderate to severe (NYHA Class III/IV) congestive heart failure (CHF) at doses greater than 5 mg/kg. Higher mortality rates at the 10 mg/kg dose and higher rates of cardiovascular events at the 5 mg/kg dose have been observed in these patients. RENFLEXIS should be used with caution and only after consideration of other treatment options. Patients should be monitored closely. Discontinue RENFLEXIS if new or worsening CHF symptoms appear. RENFLEXIS should not be (re)administered to patients who have experienced a severe hypersensitivity reaction or to patients with hypersensitivity to murine proteins or other components of the product.

HEPATITIS B REACTIVATION

TNF inhibitors, including infliximab products, have been associated with reactivation of hepatitis B virus (HBV) in patients who are chronic carriers. Some cases were fatal. Patients should be tested for HBV infection before initiating RENFLEXIS. For patients who test positive, consult a physician with expertise in the treatment of hepatitis B. Exercise caution when prescribing RENFLEXIS for patients identified as carriers of HBV and monitor closely for active HBV infection during and following termination of therapy with RENFLEXIS. Discontinue RENFLEXIS in patients who develop HBV reactivation and initiate antiviral therapy with appropriate supportive treatment. Exercise caution when considering resumption of RENFLEXIS and monitor patients closely.

HEPATOTOXICITY

Severe hepatic reactions, including acute liver failure, jaundice, hepatitis, and cholestasis have been reported rarely in patients receiving infliximab products postmarketing. Some cases were fatal or required liver transplant. Aminotransferase elevations were not noted prior to discovery of liver injury in many cases. Patients with symptoms or signs of liver dysfunction should be evaluated for evidence of liver injury. If jaundice and/or marked liver enzyme elevations (e.g., ≥5 times the upper limit of normal) develop, RENFLEXIS should be discontinued, and a thorough investigation of the abnormality should be undertaken.

HEMATOLOGIC EVENTS

Cases of leukopenia, neutropenia, thrombocytopenia, and pancytopenia (some fatal) have been reported in patients using infliximab products. The causal relationship to infliximab therapy remains unclear. Exercise caution in patients who have ongoing or a history of significant hematologic abnormalities. Advise patients to seek immediate medical attention if they develop signs and symptoms of blood dyscrasias or infection. Consider discontinuation of RENFLEXIS (infliximab-abda) in patients who develop significant hematologic abnormalities.

HYPERSENSITIVITY

Infliximab products have been associated with hypersensitivity reactions that differ in their time of onset and required hospitalization in some cases. Most hypersensitivity reactions, which include anaphylaxis, urticaria, dyspnea, and hypotension, have occurred during or within 2 hours of infusion. Serious infusion reactions including anaphylaxis were infrequent. RENFLEXIS should be discontinued for severe hypersensitivity reactions. Medications for the treatment of hypersensitivity reactions should be available.

CARDIOVASCULAR AND CEREBROVASCULAR REACTIONS DURING AND AFTER INFUSION

Serious cerebrovascular accidents, myocardial ischemia/infarction (some fatal), hypotension, hypertension, and arrhythmias have been reported during and within 24 hours of initiation of infliximab infusion. Cases of transient visual loss have been reported during or within 2 hours of infusion of infliximab. Monitor patients during infusion and, if a serious reaction occurs, discontinue infusion. Manage reactions according to signs and symptoms.

NEUROLOGIC EVENTS

TNF inhibitors, including infliximab products, have been associated in rare cases with CNS manifestation of systemic vasculitis, seizure, and new onset or exacerbation of CNS demyelinating disorders, including multiple sclerosis and optic neuritis, and peripheral demyelinating disorders, including Guillain-Barré syndrome. Exercise caution when considering RENFLEXIS in patients with these disorders and consider discontinuation if these disorders develop.

AUTOIMMUNITY

Treatment with infliximab 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.

USE WITH OTHER DRUGS

Concomitant use of RENFLEXIS with anakinra, abatacept, tocilizumab, or other biologics used to treat the same conditions as RENFLEXIS is not recommended because of the possibility of an increased risk of infection. Care should be taken when switching from one biologic to another, since overlapping biological activity may further increase the risk of infection.

LIVE VACCINES/THERAPEUTIC INFECTIOUS AGENTS

Live vaccines or therapeutic infectious agents should not be given with RENFLEXIS (infliximab-abda) due to the possibility of clinical infections, including disseminated infections. Bring pediatric patients up to date with all vaccinations prior to initiating RENFLEXIS. At least a 6-month waiting period following birth is recommended before the administration of any live vaccine to infants exposed in utero to infliximab products.

ADVERSE REACTIONS

In clinical trials with infliximab products, the most common adverse reactions occurring in >10% of patients treated with infliximab products included infections (e.g., upper respiratory, sinusitis, and pharyngitis), infusion-related reactions, headache, and abdominal pain.

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 and hematology. Samsung Bioepis is a joint venture between Samsung BioLogics and Biogen. For more information, please visit: www.samsungbioepis.com and follow us on social media – Twitter, LinkedIn.

MEDIA CONTACT

Anna Nayun Kim, +82-31-8061-1604, nayun86.kim@samsung.com

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ⁱ Remicade^® is a registered trademark of Janssen

ⁱⁱ U.S. Department of Veteran Affairs. VA Pharmaceutical Pricing Data as of October 01, 2020. Available at https://www.va.gov/opal/nac/fss/pharmPrices.asp [Last accessed October 2020]

ⁱⁱⁱ Samsung Bioepis data on file. RENFLEXIS^® was awarded a total of $117 million for the five-year national contract (2018-2023). Considering the current price gap between Remicade^® ($545.05, Big 4 price) and RENFLEXIS ^® ($121.43, National Contract price), $81,632,844 ($423.62*192,703 vials) is expected to be saved every year during the contract period, if RENFLEXIS^® is supplied 100% to the VA.

^iv “Stable IBD condition” defined as not needing oral or IV steroids for IBD management, not being hospitalized due to a disease flare, and not requiring a drug dosing or interval change for reference infliximab or infliximab-dyyb.