The FDA has granted approval to abatacept, the first drug for the prevention of graft versus host disease.
The FDA has approved abatacept (Orencia) for the prevention of acute graft versus host disease (aGVHD) in patients 2 years of age and older receiving unrelated donor hematopoietic stem cell transplantation (HSCT), according to a press release by the FDA.
This is abatacepts first cancer indication. In addition to aGVHD, the agent holds and indication for the treatment of arthritis. The label warns that abatacept should not be used in combination with JAK inhibitors or other biological agents.
“Acute graft versus host disease can affect different parts of the body and become a serious post-transplant complication,” said Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research. “By potentially preventing the disease, more patients may successfully undergo bone marrow or stem cell transplantation with fewer complications.”
The approval is based on results of the phase 2 ABA2 trial (NCT01743131). The parallel assignment study has an actual enrollment of 186 participants and an estimated completion date of February 2023. The primary end point of the study is the percentage of patients with cumulating incidence of severe aGVHD in the first 100 days after transplant. Secondary end points include incidences of severe infection, engraftment, and relapse, overall survival, rate of severe aGVHD, and the rate of severe aGVHD survival up to 180 days after transplant.
During the study, patients were randomized into a control or experimental arm. During the control arm, patients received a standard GVHD prophylaxis plus a placebo. During the experimental arm, patients received a standard GVHD prophylaxis plus abatacept.
In order to be included in the study, patients must be at least 6 years of age and weigh at least 20kg, have a willing unrelated adult donor, and a high-risk hematologic malignancy. Patients who received prior HSCT, have a willing and suitable HLC identical related donor, an HIV infection, serious psychiatric disease, an active tuberculosis infection, are pregnant or breast feeding, a cardiac ejection fraction, or pulmonary disease are not eligible to participate.
According to results from 8 patients, the rate of grade 3/4 aGVHD was 6.8% in patients who recived the abatacept versus 14.8% of those who received a placebo (HR, 0.45; 80% CI, 0.22-0.90; P =.13). Patients in the experimental cohort achieved an SGFS rate of 93.2% compared with 82% in the placebo arm (HR, 0.37; 80% CI, 0.19-0.73; P =.05).
In a cohort of 7 of the 8 patients, the incidence of aGVHD was 2.3% in the experimental arm. The combination containing abatacept led to a better SGFS rate of 97.7% compared with 58.7% in the placebo arm (P <.001).