US FDA approves the Cyltezo® Pen, A New Autoinjector Option, Ahead Of July 1 Commercial Launch

Cyltezo^® (adalimumab-adbm) will be commercially available in the U.S. beginning on July 1, 2023

Ridgefield, CT /PRNewswire/ - Boehringer Ingelheim announced today that the U.S. Food and Drug Administration (FDA) has approved the Cyltezo^® Pen, a new autoinjector option for Cyltezo (adalimumab-adbm), an FDA-approved Interchangeable biosimilar to Humira^® (adalimumab). Initially approved as a pre-filled syringe, Cyltezo is indicated to treat multiple chronic inflammatory diseases. The 40 mg/0.8 mL pre-filled Cyltezo Pen will be available in two-, four- and six-pack options on July 1, 2023.

"The FDA approval of the Cyltezo Pen is great news for patients living with chronic inflammatory diseases who may prefer administering the medication needed to manage their conditions via an autoinjector," said Stephen Pagnotta, Executive Director and Biosimilar Commercial Lead at Boehringer Ingelheim. "We're excited to be able to offer the Cyltezo Pen as an additional option to patients at Cyltezo's launch on July 1."

The patient-centered design of the pen features a one-button, three-step activation, with 100% drug visibility and a protected needle. The Arthritis Foundation has certified the Cyltezo Pen as an "Ease of Use" product. For more information about the Arthritis Foundation's "Ease of Use" certification, please visit their website.

About Biosimilars
A biosimilar is a biologic medication that is made by a different company than the one that invented it, with no clinically meaningful differences in terms of safety, potency and purity.

A biosimilar with an interchangeable designation, which is designated by the FDA, may be auto-substituted for the reference product by a pharmacist. Individual state laws control how and whether providers and patients must be notified. An interchangeable biosimilar first must meet the high FDA standards of a biosimilar – then, to receive an interchangeable designation, the FDA generally requires additional data, including a switching study where patients are switched back and forth from the reference product to the biosimilar multiple times.

About Boehringer Ingelheim in Biologics and Biosimilars
Through novel biologics and our interchangeable biosimilar, we strive to increase the availability of safe, effective, high-quality therapeutic options to patients worldwide.

Boehringer Ingelheim is one of the largest producers of biologic medicines in the world, producing biologic medicines to support our diverse pipeline, as well as other companies' biopharmaceuticals on a contract basis. As a pioneer in biologics, to date, Boehringer Ingelheim's Biopharmaceutical Contract Manufacturing business has supported our customers to bring dozens of biologics to the market in therapeutic areas that include oncology, immunology and cardiovascular indications. For more information about Boehringer Ingelheim's Biopharma and manufacturing capabilities, please click here: https://www.boehringer-ingelheim.us/biopharma/biosimilars.

To learn more about biosimilars and interchangeability please click here: Interchangeable Biosimilars.

For more information, please see full Prescribing Information, including Medication Guide and Instructions for Use.

INDICATIONS FOR CYLTEZO^® (adalimumab-adbm) injection, for subcutaneous use

Rheumatoid Arthritis: CYLTEZO is indicated 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. CYLTEZO can be used alone or in combination with methotrexate or other non-biologic disease-modifying anti-rheumatic drugs (DMARDs).

Juvenile Idiopathic Arthritis: CYLTEZO is indicated for reducing signs and symptoms of moderately to severely active polyarticular juvenile idiopathic arthritis in patients 2 years of age and older. CYLTEZO can be used alone or in combination with methotrexate.

Psoriatic Arthritis: CYLTEZO is indicated for reducing signs and symptoms, inhibiting the progression of structural damage, and improving physical function in adult patients with active psoriatic arthritis. CYLTEZO can be used alone or in combination with non-biologic DMARDs.

Ankylosing Spondylitis: CYLTEZO is indicated for reducing signs and symptoms in adult patients with active ankylosing spondylitis.

Crohn's Disease: CYLTEZO 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: CYLTEZO 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: CYLTEZO 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. CYLTEZO should only be administered to patients who will be closely monitored and have regular follow-up visits with a physician.

Hidradenitis Suppurativa: CYLTEZO is indicated for the treatment of moderate to severe hidradenitis suppurativa in adult patients

Important Safety Information For

CYLTEZO^® (adalimumab-adbm) injection, for subcutaneous use

WARNING: SERIOUS INFECTIONS and MALIGNANCY

Serious Infections

Patients treated with adalimumab products, including CYLTEZO, 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 CYLTEZO 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 CYLTEZO use and during therapy. Initiate treatment for latent TB prior to CYLTEZO 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 CYLTEZO prior to initiating therapy in patients: 1. with chronic or recurrent infection, 2. who have been exposed to TB, 3. with a history of opportunistic infection, 4. who resided in or traveled in regions where mycoses are endemic, 5. 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 CYLTEZO, including the possible development of TB in patients who tested negative for latent TB infection prior to initiating therapy.

• Do not start CYLTEZO 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 CYLTEZO 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.

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 these patients had received treatment with azathioprine or 6-mercaptopurine (6-MP) 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 prior to initiating or continuing therapy in a patient with known malignancy.
• In clinical trials of some TNF-blockers, including adalimumab products, more cases of malignancies were observed among TNF-blocker-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 PUVA therapy, for the presence of NMSC prior to and during treatment with CYLTEZO.
• 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 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.

Hypersensitivity Reactions

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

Hepatitis B Virus Reactivation

• Use of TNF blockers, including CYLTEZO, 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 CYLTEZO treatment. Discontinue CYLTEZO and begin antiviral therapy in patients who develop HBV reactivation. Exercise caution when resuming CYLTEZO after HBV treatment.

Neurologic Reactions

• 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 CYLTEZO for patients with these disorders; discontinuation of CYLTEZO should be considered if any of these disorders develop.

Hematological Reactions

• 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 CYLTEZO if significant hematologic abnormalities occur.

Congestive Heart Failure

• Worsening or new onset congestive heart failure (CHF) has been reported with TNF blockers. Cases of worsening CHF have also been observed with adalimumab. Exercise caution when using CYLTEZO in patients who have heart failure and monitor them carefully.

Autoimmunity

• 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.

Immunizations

• Patients on CYLTEZO should not receive live vaccines. Pediatric patients, if possible, should be brought up to date with all immunizations before initiating CYLTEZO therapy. 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 adalimumab clinical trials (>10%) were: infections (e.g., upper respiratory, sinusitis), injection site reactions, headache, and rash.

CL-CTZ-100008 MAR 2023

You are encouraged to report negative side effects of prescription drugs to the FDA.
Visit www.fda.gov/medwatch or call 1-800-FDA-1088.

For more information, please see full Prescribing Information, including Medication Guide and Instructions for Use.

About Boehringer Ingelheim
Boehringer Ingelheim is working on potential breakthrough therapies that transform lives, today and for generations to come. As a leading research-driven biopharmaceutical company, the company creates value through innovation in areas of high unmet medical need. Founded in 1885 and family-owned ever since, Boehringer Ingelheim takes a long-term perspective. More than 52,000 employees serve over 130 markets in the three business areas, Human Pharma, Animal Health, and Biopharmaceutical Contract Manufacturing.

For more information, please visit www.boehringer-ingelheim.us.

Boehringer Ingelheim Pharmaceuticals, Inc. either owns or uses the Cyltezo^® trademark under license. The other trademarks referenced above are owned by third parties not affiliated with Boehringer Ingelheim Pharmaceuticals, Inc.