AbbVie Submits sNDA and NDA for IMBRUVICA® (ibrutinib) to Treat Pediatric Chronic Graft Versus Host Disease (cGVHD) in the U.S.

News on March 2, 2022 /BioValleyBIOON/ -- AbbVie recently announced that it has submitted to the U.S. Food and Drug Administration (FDA) submitted a supplemental New Drug Application (sNDA) for Imbruvica (Chinese trade name: Yi Ke, generic name: ibrutinib) for the treatment of pediatric and adolescent patients aged ≥1 year with chronic graft-versus-host disease (cGVHD) who have failed prior first-line or multiple-line systemic therapies. Additionally, the company has also submitted a New Drug Application (NDA) for an Imbruvica oral suspension formulation, which aims to provide an alternative dosing option for pediatric patients.

cGVHD is hematopoieticStem CellsCommon Fatal Complications After Transplantation: Nearly Half of Patients Develop cGVHD Post-Transplant. In cGVHD, the transplanted immune cells (graft) attack the patient’s cells (host), leading to inflammation and fibrosis in multiple tissues, including the skin, mouth, eyes, joints, liver, lungs, esophagus, and gastrointestinal tract.

In the United States, there are approximately 14,000 patients with cGVHD. Currently, there are no approved treatments for children under 12 with cGVHD. If approved, Imbruvica would provide the first BTK inhibitor treatment option for pediatric and adolescent patients with cGVHD, along with an oral suspension formulation to help manage cGVHD after failure of first-line or multiple-line systemic therapies.

This sNDA and NDA are primarily based on the Phase 1/2 iMAGINE trial.Clinical TrialThe 3-year data results, including treatment with a new oral suspension. The iMAGINE trial enrolled 59 patients aged 1-19 with relapsed/refractory (R/R) or newly diagnosed moderate/severe cGVHD. The primary endpoints of the study were pharmacokinetics (PK) and safety; secondary endpoints included overall response rate (ORR).

The results showed,The ORR for Imbruvica treatment was 78%, with PK data consistent with the use of Imbruvica in adults. After 20 weeks, sustained response rates of 70% and 58% were observed in treatment-naive and R/R responders, respectively.The safety profile was consistent with the known characteristics of Imbruvica, and the observed adverse events (AEs) were consistent with those seen in adult patients with moderate to severe cGVHD. The most common ≥Grade 3 AEs (occurring in ≥5% of patients) were fever (8.5%), neutropenia (6.8%), stomatitis (6.8%), hypoxia (6.8%), osteonecrosis (6.8%), increased alanine aminotransferase (5.1%), hypokalemia (5.1%), and pneumothorax (5.1%).

Imbruvica (Yike, generic name: ibrutinib) is the world's first marketed BTK inhibitor., which was first approved in November 2013. The drug was co-developed and commercialized by Pharmacyclics, a subsidiary of AbbVie, and Janssen Pharmaceuticals, a subsidiary of Johnson & Johnson. AbbVie holds the rights for the U.S. market, while Johnson & Johnson holds the rights for markets outside the U.S.

BTK is a kinase necessary for the proliferation and dissemination of both normal and abnormal B cells. By blocking BTK, Imbruvica helps remove abnormal B cells from their growth-supportive environments, such as lymph nodes, bone marrow, and other organs. The action of Imbruvica, combined with other effects of BTK blockade, reduces the survival capability of abnormal B cells.

Since its approval for marketing in November 2013,Imbruvica has received 11 FDA approvals across six disease areas, including five B-cell blood cancers and chronic graft-versus-host disease (cGVHD).FDAApproval: With or without 17p deletion mutation (del17p) in chronic lymphocyticLeukemia(CLL), Small Lymphocytic Lymphoma (SLL) with or without 17p deletion mutation (del17p), Waldenstrom Macroglobulinemia (WM), previously treated Mantle Cell Lymphoma (MCL), Marginal Zone Lymphoma (MZL) requiring systemic therapy and having received at least one anti-CD20 therapy, Chronic Graft-Versus-Host Disease (cGVHD) failing one or more systemic therapies.

In China, Imbruvica (Yike, Ibrutinib) was approved in August 2017 as a monotherapy for the treatment of: (1) patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) who have received at least one prior therapy; (2) patients with mantle cell lymphoma (MCL) who have received at least one prior therapy. In November 2018, Imbruvica was approved for new indications: (1) as a monotherapy for patients with Waldenström's macroglobulinemia (WM) who have received at least one prior therapy or as a first-line treatment for patients unsuitable for chemoimmunotherapy; (2) in combination with rituximab for the treatment of WM patients.

Currently, AbbVie and Johnson & Johnson are advancing a large-scale Imbruvica clinicalTumorDevelopment projects. According to the annual reports released by both parties,Imbruvica's global sales reached $9.777 billion in 2021 (AbbVie: $5.408 billion, Johnson & Johnson: $4.369 billion)Analysts predict that Imbruvica's sales will reach $11.9 billion in 2025. (Bioon.com)

Source of the original text:AbbVie Seeks New Indication for IMBRUVICA? (ibrutinib) in Pediatric Patients with Chronic Graft Versus Host Disease (cGVHD)