Welcome back to the D.I.S.C.O., FDA’s Drug Information Soundcast in Clinical Oncology, Burst Edition, brought to you by FDA’s Division of Drug Information in partnership with FDA’s Oncology Center of Excellence. Today we’ll provide a quick update on a recent FDA cancer drug approval.
On December 15, 2021, the FDA approved abatacept (brand name Orencia) for the prophylaxis of acute graft versus host disease, in combination with a calcineurin inhibitor and methotrexate, in adults and pediatric patients 2 years of age and older undergoing hematopoietic stem cell transplantation from a matched or 1 allele-mismatched unrelated donor. This is the first drug approved to prevent acute graft versus host disease. The application included use of real-world data in the determination of clinical effectiveness. Real world data is clinical data routinely collected from a variety of sources, including registry data, to generate real world evidence.
Efficacy was evaluated in two studies in patients six years and older undergoing hematopoietic stem cell transplantation from a matched or 1 allele-mismatched unrelated donor.
GVHD-1 was a randomized 1:1, double-blind, placebo-controlled clinical trial of patients who underwent an 8 of 8 Human Leukocyte Antigen -matched hematopoietic stem cell transplantation and received abatacept or placebo in combination with a calcineurin inhibitor and methotrexate. While severe (grade III-IV) acute graft versus host disease-free-survival assessed at Day 180 after transplantation was not significantly improved in patients who received Orencia compared to patients who received a placebo, the overall survival rate at Day 180 after hematopoietic stem cell transplantation was 97% for patients who received abatacept compared to 84% for patients who received a placebo. The moderate-severe (grade II-IV) acute graft versus host disease -free survival rate at Day 180 after hematopoietic stem cell transplantation was 50% for patients who received abatacept compared to 32% for patients who received a placebo.
Additional evidence of effectiveness was provided by GVHD-2, a clinical study using data from the Center for International Blood and Marrow Transplant Research in patients who underwent a 7 of 8 HLA-matched hematopoietic stem cell transplantation between 2011 and 2018. This registry-based study analyzed outcomes of 54 patients treated with abatacept for the prophylaxis of acute graft versus host disease, in combination with a calcineurin inhibitor and methotrexate, versus 162 patients randomly selected from the Center for International Blood and Marrow Transplant Research registry treated with a calcineurin inhibitor and methotrexate alone. The overall survival rate at Day 180 after hematopoietic stem cell transplantation was 98% for patients who received abatacept in combination with calcineurin inhibitor and methotrexate compared to 75% for patients who received calcineurin inhibitor and methotrexate alone.
The most common adverse reactions reported in more than 10% of patients that received abatacept for the prophylaxis of acute graft versus host disease were anemia, hypertension, cytomegalovirus reactivation or cytomegalovirus infection, pyrexia, pneumonia, epistaxis, CD4 lymphocytes decreased, hypermagnesemia and acute kidney injury. Patients who receive abatacept should receive antiviral prophylaxis for Epstein-Barr virus infection before starting treatment and for six months post-transplantation and be monitored for cytomegalovirus infection or reactivation for six months post-transplant.
This review was conducted under Project Orbis, an initiative of the FDA Oncology Center of Excellence. Project Orbis provides a framework for concurrent submission and review of oncology drugs among international partners. The application reviews are ongoing at the other regulatory agencies.
This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment.
Full prescribing information for these approvals can be found on the web at www.fda.gov/drugsatFDA.
Health care professionals should report serious adverse events to FDA’s MedWatch Reporting Program at www.fda.gov/medwatch.
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