HUMIRA® Receives FDA Approval to Treat Pediatric Patients Living with Moderately to Severely Active Ulcerative Colitis

ABBVie (NYSE: ABBV) today announced that the U.S. Food and Drug Administration (FDA) approved HUMIRA ® (adalimumab) for the treatment of moderately to severely active ulcerative colitis in pediatric patients 5 years of age and older. In clinical trials, HUMIRA induced clinical remission at Week 8 and maintained remission at Week 52 in patients who responded at Week 8. 1,2

"Ulcerative colitis can have a profound effect on children and for too long, treatment options for pediatric patients have been limited," said Brandee Pappalardo , vice president and head of U.S. immunology medical affairs, AbbVie. "This approval provides the first and only subcutaneous biologic for pediatric patients with ulcerative colitis that can be administered at home. This new indication for HUMIRA demonstrates AbbVie's commitment to patients with inflammatory bowel diseases and reinforces our goal of reducing the burden of this disease for patients."

This approval is based on results from the pivotal Phase 3 ENVISION I study, which showed that HUMIRA achieved the co-primary endpoints of clinical remission per Partial Mayo Score (PMS) at Week 8 and, among those who responded at Week 8, clinical remission per Full Mayo Score (FMS) at one year (52 weeks). ^1,2 Clinical remission was defined as a PMS or as a FMS less than or equal to two and no individual sub-score greater than one. ^1,2

"Ulcerative colitis is unpredictable and affects everyone, especially children, in different ways," said Marla Dubinsky , M.D., chief, Division of Pediatric Gastroenterology for the Mount Sinai Health System and co-director of the Susan and Leonard Feinstein IBD Center at Mount Sinai.* "In the ENVISION I study, HUMIRA provided clinical response as early as Week 8, and many who achieved partial Mayo score response at Week 8 achieved clinical remission at Week 52, per FMS. As a clinician, I am excited to have a new treatment option available and am encouraged by these positive results, which have the potential to help pediatric patients and their caregivers manage their disease."

Ulcerative colitis is characterized by inflammation of the large intestine with symptoms ranging from mild to severe bowel urgency and bowel incontinence as well as weight loss and fatigue. ^3,4 It remains a lifelong condition that is not adequately controlled in many patients, underscoring the need for more treatment options. ^3,4 Significant unmet needs remain in moderate to severe pediatric ulcerative colitis, compared to adults, as pediatric patients tend to have more extensive disease often causing significant morbidity in children. ^4,5

About the ENVISION I Phase 3 Study ^1,2,6

The ENVISION I study was a Phase 3, randomized, double-blind, multicenter study designed to evaluate the efficacy, safety and the pharmacokinetics of HUMIRA in pediatric patients (ages 4-17) with moderate to severe ulcerative colitis (defined as a FMS of 6 to 12 with endoscopy subscore of 2 to 3 points, confirmed by centrally read endoscopy), administered subcutaneously.

Through Week 8, patients in both dosage groups received 2.4 mg/kg (maximum of 160 mg) at Week 0, 1.2 mg/kg (maximum of 80 mg) at Week 2, and 0.6 mg/kg (maximum of 40 mg) at Weeks 4 and 6. The higher dosage group also received an additional dosage of 2.4 mg/kg (maximum of 160 mg) at Week 1. Between Week 8 and Week 52, patients received double-blind placebo, HUMIRA 0.6 mg/kg (maximum of 40 mg) every other week, or every week. The co-primary endpoints of the study were clinical remission per PMS (defined as PMS ≤ 2 and no individual subscore > 1) at Week 8, and clinical remission per the Mayo Score (defined as Mayo Score ≤ 2 and no individual subscore > 1) at Week 52 in patients who achieved clinical response per PMS at Week 8.

Study results demonstrated 60 percent [28/47] of patients taking the higher dosage of HUMIRA achieved clinical remission per PMS, at the end of the 8-week induction period and 43 percent [13/30] of patients in the lower dosage group. At Week 52, among Week 8 PMS responders, 45 percent [14/31] of patients receiving the higher dosage of HUMIRA achieved remission per FMS and 29 percent [9/31] of patients taking the lower dosage of HUMIRA and 33 percent [4/12] of those randomized to placebo. There are limitations to the interpretability of the placebo data due to the small sample size.

Approved dosing for HUMIRA will be determined based on the child's weight, as follows ¹ :

It is recommended to continue the recommended pediatric dosage in patients who turn 18 years of age and who are well-controlled on their HUMIRA regimen.

In the ENVISION I study, no new safety signals for HUMIRA were observed. ^1,2 Throughout any HUMIRA exposure in the study, 22.6 percent of patients experienced a serious adverse event. ^1,2 The most frequently reported (greater than or equal to 5 percent) treatment-emergent adverse events during induction and maintenance periods were headache and worsening of ulcerative colitis. ⁶ No deaths, malignancies, active tuberculosis or demyelinating disease were observed in this study. ^1,2

More information on this trial can be found at www.clinicaltrials.gov (NCT02065557).

* Marla Dubinsky , M.D. is a consultant and advisor for AbbVie.

About HUMIRA (adalimumab) in the U.S.

Uses
HUMIRA is a prescription medicine used:

• To reduce the signs and symptoms of:
• Moderate to severe rheumatoid arthritis (RA) in adults. HUMIRA can be used alone, with methotrexate, or with certain other medicines. HUMIRA may prevent further damage to your bones and joints and may help your ability to perform daily activities.
• Moderate to severe polyarticular juvenile idiopathic arthritis (JIA) in children 2 years of age and older. HUMIRA can be used alone or with methotrexate.
• Psoriatic arthritis (PsA) in adults. HUMIRA can be used alone or with certain other medicines. HUMIRA may prevent further damage to your bones and joints and may help your ability to perform daily activities.
• Ankylosing spondylitis (AS) in adults.
• Moderate to severe hidradenitis suppurativa (HS)   in people 12 years and older.
• 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 and children 5 years of age and older. It is not known if HUMIRA is effective in people who stopped responding to or could not tolerate anti-TNF medicines.
• To treat moderate to severe chronic plaque psoriasis (Ps) in adults who are ready for systemic therapy or phototherapy, and are under the care of a doctor who will decide if other systemic therapies are less appropriate.
• To treat non-infectious intermediate (middle part of the eye) , posterior (back of the eye) , and panuveitis (all parts of the eye) in adults and children 2 years of age and older.

Important Safety Information About HUMIRA   ^®   (adalimumab)

What is the most important information I should know about HUMIRA?
You should discuss the potential benefits and risks of HUMIRA with your doctor. HUMIRA is a TNF blocker medicine that can lower the ability of your immune system to fight infections. You should not start taking HUMIRA if you have any kind of infection unless your doctor says it is okay.

• Serious infections have happened in people taking HUMIRA. 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 HUMIRA, and check you closely for signs and symptoms of TB during treatment with HUMIRA, 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 HUMIRA, the chance 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 HUMIRA, your chance 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 HUMIRA?
  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 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 HUMIRA. Ask your doctor if you are unsure if you have lived in these areas
• 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. HUMIRA patients may receive vaccines, except for live vaccines. Children should be brought up to date on all vaccines before starting HUMIRA
• Are allergic to rubber, latex, or any HUMIRA ingredients
• Are pregnant, planning to become pregnant, breastfeeding, or planning to breastfeed
• Have a baby and you were using HUMIRA 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 HUMIRA 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 HUMIRA?
  HUMIRA 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.

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

Remember, 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
• Weight loss
• Warm, red or painful skin sores on your body
• Diarrhea or stomach pain
• Burning when you urinate
• Urinating more often than normal
• Feeling very tired

HUMIRA is given by injection under the skin.

This is the most important information to know about HUMIRA. For more information, talk to your health care provider.

Please click here for the Full Prescribing Information and Medication Guide .

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

If you are having difficulty paying for your medicine, AbbVie may be able to help. Visit AbbVie.com/myAbbVieAssist to learn more.

Globally, prescribing information varies; refer to the individual country product label for complete information.

About AbbVie in Gastroenterology

AbbVie has focused on improving care in gastroenterology for more than 10 years. With a robust clinical trial program in inflammatory bowel disease (IBD), we are committed to cutting-edge research to drive exciting discoveries and developments in Crohn's disease and ulcerative colitis. By innovating, learning, and adapting, AbbVie aspires to eliminate the burden of IBD and make a long-term impact on the lives of people with IBD. For more information on AbbVie in gastroenterology, visit https://www.abbvie.com/our-science/therapeutic-focus-areas/immunology/immunology-focus-areas/gastroenterology.html .

About AbbVie

AbbVie's mission is to discover and deliver innovative medicines that solve serious health issues today and address the medical challenges of tomorrow. We strive to have a remarkable impact on people's lives across several key therapeutic areas: immunology, oncology, neuroscience, eye care, virology, women's health and gastroenterology, in addition to products and services across its Allergan Aesthetics portfolio. For more information about AbbVie, please visit us at www.abbvie.com . Follow @abbvie on Twitter , Facebook , Instagram , YouTube and LinkedIn .

Forward-Looking Statements

Some statements in this news release are, or may be considered, forward-looking statements for purposes of the Private Securities Litigation Reform Act of 1995. The words "believe," "expect," "anticipate," "project" and similar expressions, among others, generally identify forward-looking statements. AbbVie cautions that these forward-looking statements are subject to risks and uncertainties that may cause actual results to differ materially from those indicated in the forward-looking statements. Such risks and uncertainties include, but are not limited to, failure to realize the expected benefits from AbbVie's acquisition of Allergan plc ("Allergan"), failure to promptly and effectively integrate Allergan's businesses, competition from other products, challenges to intellectual property, difficulties inherent in the research and development process, adverse litigation or government action, changes to laws and regulations applicable to our industry and the impact of public health outbreaks, epidemics or pandemics, such as COVID-19. Additional information about the economic, competitive, governmental, technological and other factors that may affect AbbVie's operations is set forth in Item 1A, "Risk Factors," of AbbVie's 2019 Annual Report on Form 10-K, which has been filed with the Securities and Exchange Commission, as updated by its subsequent Quarterly Reports on Form 10-Q. AbbVie undertakes no obligation to release publicly any revisions to forward-looking statements as a result of subsequent events or developments, except as required by law .

References:

1. HUMIRA Prescribing Information. https://www.rxabbvie.com/pdf/humira.pdf .
2. Croft N.M., et al.  Efficacy and safety of adalimumab in pediatric patients with moderate to severe ulcerative colitis: results of a randomized-controlled phase 3 study. UEGJ . 2020;8(8S):98-99.
3. The Economic Costs of Crohn's Disease and Ulcerative Colitis. Access Economics Pty Limited. 2007. Available at: https://www.crohnsandcolitis.com.au/site/wp-content/uploads/Deloitte-Access-Economics-Report.pdf .
4. Romano, C., et al., Management of Acute Severe Colitis in Children With Ulcerative Colitis in the Biologics Era. Pediatrics. 2016;137(5):e20151184.
5. Jakobsen C., et al. Differences in phenotype and disease course in adult and paediatric inflammatory bowel disease—a population-based study. Aliment Pharmacol Ther. 2011;34(10):1217–1224pmid:21981762.
6. Efficacy and Safety of Adalimumab in Pediatric Subjects With Moderate to Severe Ulcerative Colitis. ClinicalTrials.gov. 2020. Available at: https://clinicaltrials.gov/ct2/show/record/NCT02065557 . Accessed on October 6, 2020 .

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