• The U.S. Food and Drug Administration approved the use of IMBRUVICA for the treatment of pediatric patients one year and older with cGVHD after failure of one or more lines of systemic therapy
• This is the first approved treatment option for children with cGVHD under 12 years of age and the only Bruton's tyrosine kinase inhibitor (BTKi) treatment for a pediatric patient population
• cGVHD is a rare condition that can occur in patients after receiving peripheral blood or bone marrow stem cell transplantation often related to blood cancer treatment
• IMBRUVICA was the first treatment approved in the U.S. in 2017 for adult patients with cGVHD after failure of one or more lines of systemic therapy

NORTH CHICAGO, Ill., Aug. 24, 2022 /PRNewswire/ -- AbbVie (NYSE: ABBV) today announced that the U.S. Food and Drug Administration (FDA) approved the use of IMBRUVICA^® (ibrutinib) for the treatment of pediatric patients one year and older with chronic graft versus host disease (cGVHD) after failure of one or more lines of systemic therapy.

The approval is AbbVie's first pediatric indication for IMBRUVICA, marking the 12^th FDA approval for IMBRUVICA and the first Bruton's tyrosine kinase inhibitor (BTKi) treatment approved for a pediatric patient population. This approval also marks the first approved treatment option for children under 12 years of age suffering from cGVHD. The approval is primarily based on positive results from the iMAGINE Phase 1/2 clinical trial.

cGVHD occurs when donated peripheral blood or bone marrow stem cells view the recipient's body as foreign and the donated cells launch an immune attack on the body.¹ cGVHD impacts major organs, including the skin, eyes, mouth and liver as the most commonly affected.² About 35% of the estimated 8,000 patients who undergo life-saving allogeneic hematopoietic stem cell transplant (HSCT) per year develop cGVHD that requires systemic treatment.¹ Additionally, cGVHD is the most common cause of morbidity after an allogeneic transplant.³ Steroids are the current standard treatment for pediatric cGVHD.⁴

"For a substantial fraction of children who develop moderate or severe chronic graft versus host disease after blood or marrow transplantation, treatment options supported by methodical, formal study in children are limited," said Dr. Paul A. Carpenter, attending physician at Seattle Children's Hospital and a study principal investigator. "Now, healthcare professionals have another effective treatment option for both pediatric and adult patients living with this disease after failure of one or more lines of systemic therapy. Additionally, having an oral suspension formulation designed for children is a helpful alternative."

"This approval is incredibly meaningful as AbbVie's first pediatric approval for IMBRUVICA as well as within our company's oncology portfolio. As a Pediatric Oncologist, when my patients describe the physical pain they experience from simply hugging their parents due to their cGVHD, the importance of researching alternative treatment options in this patient population is further validated," said Gauri Sunkersett, D.O., associate medical director at AbbVie. "At AbbVie, we are committed to driving oncology research and developing therapies that have the potential to help patients of all ages, including underserved populations like children diagnosed with cGVHD."

The iMAGINE study demonstrated an Overall Response Rate (ORR) through week 25 of 60% (Confidence Interval [CI] 95%; 44-74) in patients median age 13 years (range, 1-19 years) (n=47) with relapsed/refractory (R/R) moderate to severe cGVHD.⁵ The median duration of response was 5.3 months (95% CI: 2.8, 8.8).⁵ Safety was consistent with the established profile for IMBRUVICA, with observed adverse reactions (ARs) consistent with those observed in adult patients with moderate to severe cGVHD.⁵ The most common ARs (occurring in 20% or more of patients), including laboratory abnormalities, were anemia, musculoskeletal pain, pyrexia, diarrhea, pneumonia, abdominal pain, stomatitis, thrombocytopenia, and headache.⁵

Since 2017, IMBRUVICA has been approved as a single-agent therapy for adult patients with cGVHD who have experienced failure of prior systemic therapy, becoming the first FDA-approved treatment for cGVHD.

"In some ways, children struggling with cGVHD have been an 'orphan population' in relation to having treatment options available. Although there has been progress in approved treatment options for adults with cGVHD, the safety and efficacy of these have not been well studied in children," said Susan Stewart, executive director of BMT InfoNet, a non-profit advocacy organization for bone marrow, stem cell and cord blood transplant patients. "This FDA approval of IMBRUVICA gives children and their families struggling with this very difficult disease newfound hope."

The recommended dose of IMBRUVICA for cGVHD patients 12 years and older is 420 mg taken orally once daily until disease progression or unacceptable toxicity.⁶ In cGVHD patients one year old to less than 12 years of age, the recommended dose of IMBRUVICA is 240 mg/m² taken orally once daily (up to a dose of 420 mg) until disease progression or unacceptable toxicity.⁶ This FDA approval also includes an oral suspension formulation of IMBRUVICA to provide an alternative and child-friendly administration option.

About the iMAGINE Study⁵
iMAGINE (PCYC-1146-IM) is an open-label, multi-center, single-arm trial of IMBRUVICA for the treatment of pediatric and young adult patients aged one year to less than 22 years with moderate or severe cGVHD as defined by NIH Consensus Criteria. The study included 47 patients who required additional therapy after failure of one or more prior lines of systemic therapy. Patients aged 12 years and older were treated with IMBRUVICA 420 mg orally once daily, and patients aged one year to less than 12 years were treated with IMBRUVICA 240 mg/m² orally once daily. Primary endpoints included pharmacokinetics (PK) and safety, and secondary endpoints included overall response rate (ORR; CR/PR) per 2014 NIH criteria, overall survival, and duration of response (DOR).

About IMBRUVICA^®
IMBRUVICA^® (ibrutinib) is a once-daily oral medication that is jointly developed and commercialized by Janssen Biotech, Inc. and Pharmacyclics LLC, an AbbVie company. IMBRUVICA^® blocks the Bruton's tyrosine kinase (BTK) protein, which is needed by normal and abnormal B cells, including specific cancer cells, to multiply and spread. By blocking BTK, IMBRUVICA^® may help move abnormal B cells out of their nourishing environments and inhibits their proliferation.^7,8,9

IMBRUVICA^® is approved in more than 100 countries and has been used to treat more than 250,000 patients worldwide. There are more than 50 company-sponsored clinical trials, including 18 Phase 3 studies, over 11 years evaluating the efficacy and safety of IMBRUVICA^®.

IMBRUVICA^® was first approved by the U.S. Food and Drug Administration (FDA) in November 2013, and today is indicated for adult patients in six disease areas, including five hematologic cancers. These include indications to treat adults with CLL/SLL with or without 17p deletion (del17p), adults with Waldenström's macroglobulinemia (WM), adults with previously treated mantle cell lymphoma (MCL)*, adult patients with previously treated marginal zone lymphoma (MZL) who require systemic therapy and have received at least one prior anti-CD20-based therapy*, as well as adult and pediatric patients with previously treated chronic graft versus host disease (cGVHD) after failure of one or more lines of systemic therapy.⁶ 

*Accelerated approval was granted for MCL and MZL based on overall response rate. Continued approval for MCL and MZL may be contingent upon verification and description of clinical benefit in confirmatory trials.

Since 2019, the National Comprehensive Cancer Network^® (NCCN^®), recommends ibrutinib (IMBRUVICA^®) as a preferred regimen for the initial treatment of CLL/SLL and has Category 1 treatment status for treatment-naïve patients without deletion 17p/TP53 mutation and as a preferred treatment for treatment-naïve patients with deletion 17p/TP53 mutation. The NCCN Guidelines^® also recommend IMBRUVICA^®, with or without rituximab, as a preferred regimen for the treatment of relapsed/refractory MCL, as a Category 1 preferred regimen for both untreated and previously treated WM patients, and as a preferred regimen for relapsed/refractory MZL.¹⁰

For more information, visit www.IMBRUVICA.com.

IMPORTANT SAFETY INFORMATION

Before taking IMBRUVICA^®, tell your healthcare provider about all of your medical conditions, including if you:

• have had recent surgery or plan to have surgery. Your healthcare provider may stop IMBRUVICA^® for any planned medical, surgical, or dental procedure.
• have bleeding problems
• have or had heart rhythm problems, smoke, or have a medical condition that increases your risk of heart disease, such as high blood pressure, high cholesterol, or diabetes
• have an infection
• have liver problems
• are pregnant or plan to become pregnant. IMBRUVICA^® can harm your unborn baby. If you are able to become pregnant, your healthcare provider will do a pregnancy test before starting treatment with IMBRUVICA^®. Tell your healthcare provider if you are pregnant or think you may be pregnant during treatment with IMBRUVICA^®.
  • Females who are able to become pregnant should use effective birth control (contraception) during treatment with IMBRUVICA^® and for 1 month after the last dose.
  • Males with female partners who are able to become pregnant should use effective birth control, such as condoms, during treatment with IMBRUVICA^® and for 1 month after the last dose.
• are breastfeeding or plan to breastfeed.  Do not breastfeed during treatment with IMBRUVICA^® and for 1 week after the last dose.

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Taking IMBRUVICA^® with certain other medicines may affect how IMBRUVICA^® works and can cause side effects.

How should I take IMBRUVICA^®?

• Take IMBRUVICA^® exactly as your healthcare provider tells you to take it.
• Take IMBRUVICA^® 1 time a day at about the same time each day.

IMBRUVICA^® comes as capsules, tablets, and oral suspension.

• If your healthcare provider prescribes IMBRUVICA^® capsules or tablets:
  • Swallow IMBRUVICA^® capsules or tablets whole with a glass of water.
  • Do not open, break, or chew IMBRUVICA^® capsules.
  • Do not cut, crush, or chew IMBRUVICA^® tablets.
• If your healthcare provider prescribes IMBRUVICA^® oral suspension:
  • See the detailed Instructions for Use that comes with IMBRUVICA^® oral suspension for information about the correct way to give a dose to your child. If you have questions about how to give IMBRUVICA^® oral suspension, talk to your healthcare provider.
  • Do not use if the carton seal is broken or missing.
• If you miss a dose of IMBRUVICA^® take it as soon as you remember on the same day. Take your next dose of IMBRUVICA^® at your regular time on the next day. Do not take extra doses of IMBRUVICA^® to make up for a missed dose.
• If you take too much IMBRUVICA^® call your healthcare provider or go to the nearest hospital emergency room right away.

What should I avoid while taking IMBRUVICA^®?

• You should not drink grapefruit juice, eat grapefruit, or eat Seville oranges (often used in marmalades) during treatment with IMBRUVICA^®. These products may increase the amount of IMBRUVICA^® in your blood.

What are the possible side effects of IMBRUVICA^®?
IMBRUVICA^® may cause serious side effects, including:

• Bleeding problems (hemorrhage) are common during treatment with IMBRUVICA^®, and can also be serious and may lead to death. Your risk of bleeding may increase if you are also taking a blood thinner medicine. Tell your healthcare provider if you have any signs of bleeding, including: blood in your stools or black stools (looks like tar), pink or brown urine, unexpected bleeding, or bleeding that is severe or that you cannot control, vomit blood or vomit looks like coffee grounds, cough up blood or blood clots, increased bruising, dizziness, weakness, confusion, change in your speech, or a headache that lasts a long time or severe headache.
• Infections can happen during treatment with IMBRUVICA^®. These infections can be serious and may lead to death. Tell your healthcare provider right away if you have fever, chills, weakness, confusion, or other signs or symptoms of an infection during treatment with IMBRUVICA^®.
• Heart problems. Serious heart rhythm problems (ventricular arrhythmias, atrial fibrillation and atrial flutter), heart failure and death have happened in people treated with IMBRUVICA^®, especially in people who have an infection, an increased risk for heart disease, or have had heart rhythm problems in the past. Your heart function will be checked before and during treatment with IMBRUVICA^®. Tell your healthcare provider if you get any symptoms of heart problems, such as feeling as if your heart is beating fast and irregular, lightheadedness, dizziness, shortness of breath, swelling of the feet, ankles or legs, chest discomfort, or you faint. If you develop any of these symptoms, your healthcare provider may do tests to check your heart and may change your IMBRUVICA^® dose.
• High blood pressure (hypertension). New or worsening high blood pressure has happened in people treated with IMBRUVICA^®. Your healthcare provider may start you on blood pressure medicine or change current medicines to treat your blood pressure.
• Decrease in blood cell counts. Decreased blood counts (white blood cells, platelets, and red blood cells) are common with IMBRUVICA^®, but can also be severe. Your healthcare provider should do monthly blood tests to check your blood counts.
• Second primary cancers. New cancers have happened during treatment with IMBRUVICA^®, including cancers of the skin or other organs.
• Tumor lysis syndrome (TLS). TLS is caused by the fast breakdown of cancer cells. TLS can cause kidney failure and the need for dialysis treatment, abnormal heart rhythm, seizure, and sometimes death. Your healthcare provider may do blood tests to check you for TLS.

The most common side effects of IMBRUVICA^® in adults with B-cell malignancies (MCL, CLL/SLL, WM and MZL) include:

• diarrhea
• tiredness
• muscle and bone pain
• rash
• bruising

The most common side effects of IMBRUVICA^® in adults or children 1 year of age and older with cGVHD include:

• tiredness
• low red blood cell count (anemia)
• bruising
• diarrhea
• low platelet count
• muscle and joint pain
• fever
• muscle spasms
• mouth sores (stomatitis)
• bleeding
• nausea
• stomach pain
• pneumonia
• headache

Diarrhea is a common side effect in people who take IMBRUVICA^®. Drink plenty of fluids during treatment with IMBRUVICA^® to help reduce your risk of losing too much fluid (dehydration) due to diarrhea. Tell your healthcare provider if you have diarrhea that does not go away.

These are not all the possible side effects of IMBRUVICA^®. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

General information about the safe and effective use of IMBRUVICA^®
Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use IMBRUVICA^® for a condition for which it was not prescribed. Do not give IMBRUVICA^® to other people, even if they have the same symptoms that you have. It may harm them. You can ask your pharmacist or healthcare provider for information about IMBRUVICA^® that is written for health professionals.

Please see the full Important Product Information.

Uses
What is IMBRUVICA^® (ibrutinib)?
IMBRUVICA^® (ibrutinib) is a prescription medicine used to treat:

• Adults with mantle cell lymphoma (MCL) who have received at least one prior treatment.
• Adults with chronic lymphocytic leukemia (CLL)/Small lymphocytic lymphoma (SLL).
• Adults with chronic lymphocytic leukemia (CLL)/Small lymphocytic lymphoma (SLL) with 17p deletion.
• Adults with Waldenström's macroglobulinemia (WM).
• Adults with marginal zone lymphoma (MZL) who require a medicine by mouth or injection (systemic therapy) and have received a certain type of prior treatment.
• Adults and children 1 year of age and older with chronic graft versus host disease (cGVHD) after failure of 1 or more lines of systemic therapy.

It is not known if IMBRUVICA^® is safe and effective in children under 1 year of age.

About AbbVie in Oncology
At AbbVie, we are committed to transforming standards of care for multiple blood cancers while advancing a dynamic pipeline of investigational therapies across a range of cancer types. Our dedicated and experienced team joins forces with innovative partners to accelerate the delivery of potentially breakthrough medicines. We are evaluating more than 20 investigational medicines in over 300 clinical trials across some of the world's most widespread and debilitating cancers. As we work to have a remarkable impact on people's lives, we are committed to exploring solutions to help patients obtain access to our cancer medicines. For more information, please visit http://www.abbvie.com/oncology.

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 2021 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.

IMBRUVICA is a registered trademark of Pharmacyclics LLC.

SOURCE AbbVie