US FDA approves Boehringer Ingelheim’s high-concentration, citrate-free formulation of Cyltezo® (adalimumab-adbm) injection

RIDGEFIELD, Conn., May 1, 2024 /PRNewswire/ -- Boehringer Ingelheim announced today that the U.S. Food and Drug Administration (FDA) has approved the high-concentration, citrate-free formulation of Cyltezo® (adalimumab-adbm) to treat multiple chronic inflammatory diseases.

"With this FDA approval, we are now able to offer both high- and low-concentration, citrate-free formulations of Cyltezo, further expanding treatment access for patients living with certain chronic inflammatory diseases," said Stephen Pagnotta, Executive Director and Biosimilar Commercial Lead at Boehringer Ingelheim. "Many patients are treated with high-concentration adalimumab formulations, and we are excited to add this new option to our approved citrate-free Cyltezo and Adalimumab-adbm offerings."

The high-concentration formulation (100 mg/mL), which is now available as a pre-filled syringe or pre-filled autoinjector, is priced at a 5% discount to Humira under the brand name Cyltezo® and at an 81% discount to Humira as the unbranded product Adalimumab-adbm. The low-concentration (50 mg/mL), citrate-free formulation of Cyltezo has been commercially available since July 2023.

"The availability of a high-concentration and citrate-free Cyltezo is welcome news for people living with certain chronic inflammatory conditions, such as Crohn's disease and ulcerative colitis, which affect nearly 1 in 100 Americans," said Michael Osso, President & CEO of the Crohn's & Colitis Foundation. "The flexibility of having multiple biosimilar formulations to choose from is important to support broader patient access to biologic medicines."

"This FDA approval is another step forward for people with chronic and often debilitating diseases such as rheumatoid and psoriatic arthritis," said Steven Taylor, President & CEO of the Arthritis Foundation. "We stand united with our patients and healthcare providers in the effort to accelerate the adoption of biosimilars, which benefit patients as well as the larger healthcare ecosystem."

"Biologics and biosimilars are a crucial treatment option for many living with psoriatic arthritis or psoriasis," said Leah M. Howard, J.D., President and CEO of the National Psoriasis Foundation. "We welcome the introduction of this additional formulation to expand the array of options available to our community."

The FDA approval is based, in part, on data from clinical trial VOLTAIRE-HCLF, a Phase I clinical trial comparing the bioavailability of high-concentration and low-concentration formulations of adalimumab-adbm.

About Cyltezo
The FDA approved Cyltezo as an interchangeable* biosimilar (50 mg/mL) to Humira on October 15, 2021. The FDA has provisionally determined our high-concentration formulation (100 mg/mL) meets the interchangeability criteria under section 351(k) of the PHS Act, however, FDA has not yet granted the interchangeability designation for our high-concentration formulation due to an unexpired period of interchangeability exclusivity. 

The efficacy and safety of Cyltezo are supported by a large body of data, including the Phase III randomized VOLTAIRE-X comparative clinical trial, which studied the effects of multiple switches between Humira and Cyltezo compared to continuous treatment with Humira. To learn more about Cyltezo, please visit Cyltezo.com. Healthcare providers can learn more about Cyltezo at CyltezoHCP.com.

*For more information on interchangeability for Cyltezo, please refer to the Purple Book: https://purplebooksearch.fda.gov/.

About Biosimilars
A biosimilar is a biologic medicine that is developed to be highly similar to an approved reference biologic, 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 achieve the interchangeable designation, the FDA requires additional data, which may include a study of multiple substitutions in patients, known as a switching study. The study must show that patients can be switched with no increased risk in terms of safety or diminished efficacy compared with remaining on the reference product in any given patient.

About Boehringer Ingelheim in Biologics and Biosimilars
Through novel biologics and our 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.com/us/biopharma/biosimilars.

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

What is CYLTEZO?

This information also applies to Adalimumab-adbm injection for subcutaneous use.

CYLTEZO is a medicine called a tumor necrosis factor (TNF) blocker. CYLTEZO is used:

• To reduce the signs and symptoms of:
  • moderate to severe rheumatoid arthritis (RA) in adults. CYLTEZO can be used alone, with methotrexate, or with certain other medicines.
  • moderate to severe polyarticular juvenile idiopathic arthritis (JIA) in children 2 years and older. CYLTEZO can be used alone or with methotrexate.
  • psoriatic arthritis (PsA) in adults. CYLTEZO can be used alone or with certain other medicines.
  • ankylosing spondylitis (AS) in adults.
  • moderate to severe hidradenitis suppurativa (HS) in adults.
• To treat moderate to severe Crohn's disease (CD) in adults and children 6 years of age and older.
• To treat moderate to severe ulcerative colitis (UC) in adults. It is not known if adalimumab products are effective in people who stopped responding to or could not tolerate TNF-blocker medicines.
• To treat moderate to severe chronic (lasting a long time) plaque psoriasis (Ps) in adults who have the condition in many areas of their body and who may benefit from taking injections or pills (systemic therapy) or phototherapy (treatment using ultraviolet light alone or with pills).
• To treat non-infectious intermediate, posterior, and panuveitis in adults.

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

This important information also applies to Adalimumab-adbm injection for subcutaneous use.

What is the most important information I should know about CYLTEZO?

You should discuss the potential benefits and risks of CYLTEZO with your doctor. CYLTEZO is a TNF-blocker medicine that can lower the ability of your immune system to fight infections. You should not start taking CYLTEZO if you have any kind of infection unless your doctor says it is okay.

• Serious infections have happened in people taking adalimumab products. These serious infections include tuberculosis (TB) and infections caused by viruses, fungi, or bacteria that have spread throughout the body. Some people have died from these infections. Your doctor should test you for TB before starting CYLTEZO and check you closely for signs and symptoms of TB during treatment with CYLTEZO, even if your TB test was negative. If your doctor feels you are at risk, you may be treated with medicine for TB.
• Cancer. For children and adults taking TNF blockers, including CYLTEZO, the chances of getting lymphoma or other cancers may increase. There have been cases of unusual cancers in children, teenagers, and young adults using TNF blockers. Some people have developed a rare type of cancer called hepatosplenic T-cell lymphoma. This type of cancer often results in death. If using TNF blockers, including CYLTEZO, your chances of getting two types of skin cancer (basal cell and squamous cell) may increase. These types are generally not life-threatening if treated; tell your doctor if you have a bump or open sore that doesn't heal.

What should I tell my doctor BEFORE starting CYLTEZO?

Tell your doctor about all of your health conditions, including if you:

• Have an infection, are being treated for infection, or have symptoms of an infection.
• Get a lot of infections or have infections that keep coming back.
• Have diabetes.
• Have TB or have been in close contact with someone with TB, or were born in, lived in, or traveled where there is more risk for getting TB.
• Live or have lived in an area (such as the Ohio and Mississippi River valleys) where there is an increased risk for getting certain kinds of fungal infections, such as histoplasmosis, coccidioidomycosis, or blastomycosis. These infections may happen or become more severe if you use CYLTEZO. Ask your doctor if you are unsure whether you have lived in an area where these infections are common.
• Have or have had hepatitis B.
• Are scheduled for major surgery.
• Have or have had cancer.
• Have numbness or tingling or a nervous system disease such as multiple sclerosis or Guillain-Barré syndrome.
• Have or had heart failure.
• Have recently received or are scheduled to receive a vaccine. CYLTEZO patients may receive vaccines, except for live vaccines. Children should be brought up to date on all vaccines before starting CYLTEZO.
• Are allergic to rubber or latex.
• Are allergic to any CYLTEZO ingredients.
• Are pregnant, planning to become pregnant, breastfeeding, or planning to breastfeed.
• Have a baby and you were using CYLTEZO during your pregnancy. Tell your baby's doctor before your baby receives any vaccines.

Also tell your doctor about all the medicines you take. You should not take CYLTEZO with ORENCIA® (abatacept), KINERET® (anakinra), REMICADE® (infliximab), ENBREL® (etanercept), CIMZIA® (certolizumab pegol), or SIMPONI® (golimumab). Tell your doctor if you have ever used RITUXAN® (rituximab), IMURAN® (azathioprine), or PURINETHOL® (mercaptopurine, 6-MP).

What should I watch for AFTER starting CYLTEZO?

CYLTEZO can cause serious side effects, including:

• Serious infections. These include TB and infections caused by viruses, fungi, or bacteria. Symptoms related to TB include a cough, low-grade fever, weight loss, or loss of body fat and muscle.
• Hepatitis B infection in carriers of the virus. Symptoms include muscle aches, feeling very tired, dark urine, skin or eyes that look yellow, little or no appetite, vomiting, clay-colored bowel movements, fever, chills, stomach discomfort, and skin rash.
• Allergic reactions. Symptoms of a serious allergic reaction include hives; trouble breathing; and swelling of your face, eyes, lips, or mouth.
• Nervous system problems. Signs and symptoms include numbness or tingling, problems with your vision, weakness in your arms or legs, and dizziness.
• Blood problems (decreased blood cells that help fight infections or stop bleeding). Symptoms include a fever that does not go away, bruising or bleeding very easily, or looking very pale.
• Heart failure (new or worsening). Symptoms include shortness of breath, swelling of your ankles or feet, and sudden weight gain.
• Immune reactions, including a lupus-like syndrome. Symptoms include chest discomfort or pain that does not go away, shortness of breath, joint pain, or rash on your cheeks or arms that gets worse in the sun.
• Liver problems. Symptoms include feeling very tired, skin or eyes that look yellow, poor appetite or vomiting, and pain on the right side of your stomach (abdomen). These problems can lead to liver failure and death.
• Psoriasis (new or worsening). Symptoms include red scaly patches or raised bumps that are filled with pus.

Call your doctor or get medical care right away if you develop any of the above symptoms.

The most common side effects of CYLTEZO include injection site reactions (pain, redness, rash, swelling, itching, or bruising), upper respiratory infections (sinus infections), headaches, and rash. These are not all the possible side effects with CYLTEZO. Tell your doctor if you have any side effect that bothers you or that does not go away.

Remember to tell your doctor right away if you have an infection or symptoms of an infection, including:

• Fever, sweats, or chills
• Muscle aches
• Cough
• Shortness of breath
• Blood in phlegm
• Warm, red, or painful skin or sores on your body
• Diarrhea or stomach pain
• Burning when you urinate
• Urinating more often than normal
• Feeling very tired
• Weight loss

These are not all the possible side effects of CYLTEZO. For more information, speak with your doctor or pharmacist.

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. 

CL-CTZ-100017 SEPT 2023

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

About Boehringer Ingelheim
Boehringer Ingelheim is a biopharmaceutical company active in both human and animal health. As one of the industry’s top investors in Research and Development, the company focuses on developing innovative therapies in areas of high unmet medical need. Independent since its foundation in 1885, Boehringer takes a long-term perspective, embedding sustainability along the entire value chain. More than 53,500 employees serve over 130 markets to build a healthier, more sustainable, and equitable tomorrow. Discover more at www.boehringer-ingelheim.com/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.

MPR-US-103133 (5/24)

Media Contact:
Taylor Pepe
Senior Associate Director, Human Pharma Communications
[email protected]

SOURCE Boehringer Ingelheim Pharmaceuticals, Inc.