Boehringer Ingelheim Pharmaceuticals, Inc. receives FDA approval for Cyltezo™ (adalimumab-adbm), a biosimilar to Humira®, for the treatment of multiple chronic inflammatory diseases

- Cyltezo™ is the first biosimilar from Boehringer Ingelheim to be approved by the FDA, building on 35 years of biologics manufacturing expertise

- Robust analytical, pharmacological, non-clinical and clinical data demonstrates that Cyltezo™ is biosimilar to Humira®*

News provided by

Boehringer Ingelheim Pharmaceuticals, Inc.

Aug 29, 2017, 09:26 ET

RIDGEFIELD, Conn., Aug. 29, 2017 /PRNewswire/ -- Boehringer Ingelheim Pharmaceuticals, Inc. today announced that the U.S. Food and Drug Administration (FDA) approved Cyltezo^™, a biosimilar to Humira^®, in a pre-filled syringe for the treatment of multiple chronic inflammatory diseases, including:

moderate to severe active rheumatoid arthritis
moderate to severe polyarticular juvenile idiopathic arthritis**
active psoriatic arthritis
active ankylosing spondylitis (an arthritis that affects the spine)
moderate to severe active adult Crohn's disease
moderate to severe active ulcerative colitis
moderate to severe plaque psoriasis

"Cyltezo^™ is the first biosimilar from Boehringer Ingelheim to be approved by the FDA and marks an important step towards our goal of providing new and more affordable treatment options to healthcare providers and patients," said Ivan Blanarik, Senior Vice President and Head of Therapeutic Area Biosimilars at Boehringer Ingelheim. "Chronic inflammatory diseases collectively affect 23.5 million people in the U.S., and Cyltezo^™ has the potential to deliver significant benefits to many of these individuals."

The FDA approval is based on a comprehensive data package comprised of analytical, pharmacological, non-clinical and clinical development studies demonstrating that Cyltezo^™ is biosimilar to Humira^®.

The European Medicines Agency is expected to provide an opinion on the marketing authorization application for our biosimilar candidate in 2017.

Cyltezo^™ is not commercially available at this time. Boehringer Ingelheim is currently engaged in patent litigation with AbbVie. Boehringer Ingelheim will also seek approval for an auto-injector of Cyltezo^™, as another delivery option for patients.

About Cyltezo^™ (adalimumab-adbm) injection, for subcutaneous use

Rheumatoid Arthritis: CYLTEZO 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: CYLTEZO is indicated, alone or in combination with methotrexate, for reducing signs and symptoms of moderately to severely active polyarticular juvenile idiopathic arthritis in patients 4 years of age and older.

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

Adult Crohn's Disease: CYLTEZO is indicated for reducing signs and symptoms and inducing and maintaining clinical remission in adult patients with moderately to severely active Crohn's disease who have had an inadequate response to conventional therapy, and reducing signs and symptoms and inducing clinical remission in these patients if they have also lost response to or are intolerant to infliximab.

Ulcerative Colitis: CYLTEZO is indicated for inducing and sustaining clinical remission in adult patients with moderately to severely active ulcerative colitis who have had an inadequate response to immunosuppressants such as corticosteroids, azathioprine or 6-mercaptopurine (6-MP). The effectiveness of CYLTEZO 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.

IMPORTANT SAFETY INFORMATION FOR CYLTEZO^™
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

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. 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.

Please see full Prescribing Information, including Medication Guide.

About Boehringer Ingelheim in Biologics and Biosimilars
Boehringer Ingelheim is one of the largest producers of biologic medicines in the world. As a pioneer in biologics with more than 35 years of experience, the company has manufactured more than 25 biologic medicines for global markets. This includes monoclonal antibodies in immunology and oncology, interferons, and other targeted medicines that are routinely used to treat many patients across a broad range of therapeutic areas. For more information about Boehringer Ingelheim's Biopharma and manufacturing capabilities, please click here https://www.boehringer-ingelheim.us/biopharma/biosimilars

Boehringer Ingelheim further builds on its commitment to immunology and oncology to develop biosimilars as high quality, safe, and effective treatment options to patients with autoimmune diseases and cancer. In addition to Cyltezo^™ (adalimumab-adbm), Boehringer Ingelheim currently has BI 695502, a bevacizumab biosimilar candidate to Avastin^®* in late stage development. Also ongoing is VOLTAIRE-X, an interchangeability study with Cyltezo^™ and the U.S.-marketed formulation of Humira^®, 40mg/0.8mL. All public information on our clinical trials is available on: http://clinicaltrials.gov/.

*Humira^® is a registered trademark of AbbVie, Inc. and Avastin^® is a registered trademark of Genentech, Inc. (USA).
**(Four years of age and older)

About Boehringer Ingelheim Pharmaceuticals, Inc.
Boehringer Ingelheim Pharmaceuticals, Inc., based in Ridgefield, CT, is the largest U.S. subsidiary of Boehringer Ingelheim Corporation.

Boehringer Ingelheim is one of the world's top 20 pharmaceutical companies. Headquartered in Ingelheim, Germany, the company operates globally with approximately 50,000 employees. Since its founding in 1885, the company has remained family-owned and today creates value through innovation for three business areas including human pharmaceuticals, animal health and biopharmaceutical contract manufacturing.

Boehringer Ingelheim is committed to improving lives and providing valuable services and support to patients and their families. Our employees create and engage in programs that strengthen our communities. Please visit our website to learn more about how we make more health for more people through our Corporate Social Responsibility initiatives.

In 2016, Boehringer Ingelheim achieved net sales of about $17.6 billion (15.9 billion euros). R&D expenditure corresponds to 19.6 percent of its net sales.

For more information please visit www.boehringer-ingelheim.us, or follow us on Twitter @BoehringerUS.

SOURCE Boehringer Ingelheim Pharmaceuticals, Inc.