資料來源：https://www.prnewswire.com/news-releases/us-fda-approves-imbruvica-ibrutinib-as-first-and-only-approved-treatment-for-adult-patients-with-chronic-graft-versus-host-disease-cgvhd-after-failure-of-one-or-more-lines-of-systemic-therapy-300498520.html

The U.S. Food and Drug Administration (FDA) has approved IMBRUVICA® (ibrutinib) for the treatment of adult patients with chronic graft-versus-host-disease (cGVHD) after failure of one or more lines of systemic therapy.1 IMBRUVICA is the first and only FDA-approved medication for adult patients with cGVHD, a potential consequence of an allogeneic stem cell or bone marrow transplant, which can be life-threatening and debilitating.2 IMBRUVICA is a first-in-class Bruton's tyrosine kinase (BTK) inhibitor jointly developed and commercialized by Janssen Biotech, Inc., and Pharmacyclics LLC, an AbbVie company.

"Chronic graft-versus-host-disease can occur after allogeneic stem cell or bone marrow transplant and results from donor immune cells attacking the patient's tissue. For most patients, the diagnosis of cGVHD comes after a long and already arduous battle with a blood-related disease," said David Miklos, M.D., Ph.D., Associate Professor of Medicine (Blood and Marrow Transplantation), Stanford University, and lead investigator of the IMBRUVICA cGVHD clinical study.* "This approval provides physicians and the cGVHD patient community with a welcome new approach for patients who fail initial therapy, as data show treatment with IMBRUVICA resulted in encouraging and sustained clinical responses." 

The approval is based on results from an open-label, multi-center, single-arm Phase 1b/2 trial (PCYC-1129) evaluating the safety and efficacy of ibrutinib in 42 patients with cGVHD who failed first-line corticosteroid therapy and required additional therapy (median age of 56 years; range, 19 to 74 years old). In the study population, the most common underlying malignancies leading to transplantation were acute lymphocytic leukemia (ALL), acute myeloid leukemia (AML) and chronic lymphocytic leukemia (CLL). The median time since cGVHD diagnosis was 14 months, the median number of prior cGVHD treatments was two (range, one to three treatments), and 60% of patients had a Karnofsky performance score of ≤ 80. The majority of patients (88%) had at least two organs involved at the beginning of the trial, with the most commonly involved organs being mouth (86%), skin (81%) and gastrointestinal tract (33%). Fifty-two percent of patients were receiving ongoing immunosuppressants in addition to systemic corticosteroids at baseline.1

The overall response rate (ORR) was 67% (95% CI: 51%, 80%), with 21% of patients achieving complete responses (CR; n=9) and 45% achieving partial responses (PR; n=19). Sustained response rate of at least 20 weeks was 48% (n=20). The median time to best response coinciding with the first scheduled response assessment was 12.3 weeks (range, 4.1 to 42.1 weeks). Responses were seen across all involved organs for cGVHD (i.e., skin, mouth, gastrointestinal tract and liver).1

Warnings and precautions for IMBRUVICA include hemorrhage, infections, cytopenias, atrial fibrillation, hypertension, second primary malignancies, tumor lysis syndrome and embryo-fetal toxicity. The most common (>20%) adverse events (AEs) of all Grades in the cGVHD trial included fatigue (57%), bruising (40%), diarrhea (36%), thrombocytopenia (33%), stomatitis (29%), muscle spasms (29%), nausea (26%), hemorrhage (26%), anemia (24%), and pneumonia (21%). Atrial fibrillation occurred in one patient (2%), which was Grade 3. Twenty-four percent of patients receiving IMBRUVICA in the cGVHD trial discontinued treatment due to adverse reactions. The most common adverse reactions leading to discontinuation were fatigue and pneumonia. Adverse reactions leading to dose reduction occurred in 26% of patients.1

"We are very pleased to bring IMBRUVICA to physicians and patients battling chronic graft-versus-host-disease," said Peter F. Lebowitz, M.D., Ph.D., Global Oncology Head, Janssen. "This indication for previously-treated cGVHD represents the first approved use of IMBRUVICA outside of the hematology-oncology category, and we are deeply proud of this development."

The data was presented as a late-breaker at the American Society of Hematology Annual Meeting in December 2016 and the Blood and Marrow Transplantation Tandem Meeting in February 2017. A Phase 3 double-blind, placebo-controlled study was initiated in December 2016 to examine ibrutinib with corticosteroid versus placebo with corticosteroid as a first-line therapy for patients with new onset moderate or severe cGVHD; the study is ongoing.

Patients can develop GVHD, a potentially life-threatening complication, following an allogeneic stem cell or bone marrow transplant.2 The condition occurs when donor immune cells mistakenly attack the patients' normal tissues.2 The effects of cGVHD can be seen throughout the body, affecting almost any organ, which may include loss of patches of skin, hair loss, excessive dryness of the body resulting in ulcers and scarring of the lungs, and liver injury leading to liver failure.2 The incidence of cGVHD has continued to increase over time,3 with approximately 30-70% of post-allogeneic transplant patients developing the condition.4

Janssen and Pharmacyclics are continuing an extensive clinical development program for IMBRUVICA, including Phase 3 study commitments in multiple disease areas.

About IMBRUVICA

IMBRUVICA® (ibrutinib) was one of the first therapies to receive U.S. approval after having received the FDA's Breakthrough Therapy Designation. IMBRUVICA works by blocking a specific protein called Bruton's tyrosine kinase (BTK).1 The BTK protein transmits important signals that tell B cells to mature and produce antibodies and is needed by specific cancer cells to multiply and spread.5 IMBRUVICA targets and blocks BTK, inhibiting the survival and spread of cancer cells, and impacting signaling associated with other serious conditions.