Novartis announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has adopted a positive opinion recommending approval of Jakavi® (ruxolitinib) for the treatment of patients aged 12 years and older with acute graft versus host disease or chronic graft versus host disease (GvHD) who have inadequate response to corticosteroids or other systemic therapies. If approved, Jakavi will be the first JAK1/2 inhibitor available for patients with GvHD in Europe.
“For many hematologic diseases, allogeneic transplant is the only treatment with the potential to be curative; however, half will go on to develop acute or chronic GvHD,” said Dr. Robert Zeiser, University Hospital Freiburg, Department of Haematology, Oncology and Stem Cell Transplantation, Freiburg, Germany. “It is encouraging that we may soon have a new standard of care for patients with this often debilitating condition who do not adequately respond to first-line corticosteroids or other systemic therapies.”
The CHMP positive opinion was based on data from the Phase III REACH2 and REACH3 clinical studies, in which Jakavi demonstrated superiority versus best available therapy (BAT) in patients with steroid-refractory and steroid-dependent acute and chronic GvHD, respectively.
Results from the REACH2 trial showed that overall response rate (ORR) at Day 28 was superior in the Jakavi arm at 62.3% vs. 39.4% in the BAT arm (odds ratio [OR], 2.64; p<0.001) in patients with steroid-refractory/dependent acute GvHD. In those patients who maintained response at Day 56, the ORR in the Jakavi arm was 40% vs. 22% in the BAT arm (p<0.001). In REACH3, treatment with Jakavi led to significant improvements in ORR compared to BAT (49.7% vs. 25.6%; OR, 2.99; P<0.0001) in patients with steroid-refractory/dependent chronic GvHD at week 24, the primary endpoint of the study, regardless of the individual organs involved at baseline.
Also, best overall response (BOR) rate at any time up to week 24 was achieved in 76.4% of patients in the Jakavi arm compared to 60.4% in the BAT arm (OR, 2.17; 95% CI, 1.34-3.52). Results from the two studies were published in the April 22, 2020 (REACH2), and July 15, 2021 (REACH3) issues of The New England Journal of Medicine.
GvHD, a common and potentially life-threatening complication that can arise after allogeneic stem cell transplants, is a reaction where the donor’s cells see the recipient’s normal cells as foreign and attack them. Symptoms of GvHD can appear in the skin, gastrointestinal tract, liver, mouth, eyes, genitals, lungs, and joints.
Approximately 50 percent of allogeneic stem cell transplant recipients experience either acute or chronic GvHD, or both4. Acute GvHD typically occurs within the first 100 days of transplant, while chronic GvHD generally occurs more than 100 days after transplant. Both acute and chronic GvHD can be fatal and until now both have lacked an established standard of care for patients who do not adequately respond to first-line steroid treatment.
“This positive CHMP opinion for Jakavi in GvHD brings us one step closer to approval in Europe, for a condition where patients often experience severe and life-threatening symptoms,” said Susanne Schaffert, PhD, President, Novartis Oncology. “With this exciting news, we may change the way GvHD is treated as about half of patients do not respond to previous corticosteroids or other systemic treatment.”
The CHMP’s positive opinion of Jakavi in acute and chronic GvHD will be referred to the European Commission (EC), which has the authority to grant marketing authorizations for medications in the EU. The EC will review the CHMP recommendations and is expected to make a final decision within approximately 2 months.
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