2020-12-06| Trials & Approvals

ASH2020: Incyte Presents Positive Phase 3 Data for cGVHD Drug, Ruxolitinib

by Ruchi Jhonsa
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Leukemic and lymphoma patients often resort to stem cell transplants (SCT) for rejuvenating their debilitating immune system. Similar to an organ transplant, stem cell transplant involves extracting stem cells from a donor and transplanting them into the patient. During this process, the body could accept the new cells. However, 30% to 70% of patients who undergo SCT are affected by chronic graft versus host disease (cGVHD) wherein donor’s T cells (the graft) view the patient’s healthy cells (the host) as foreign and attack and damage them. This is a leading cause of nonrelapse mortality and morbidity.

For cGVHD, the standard first-line therapy consists of systemic steroids. However, repeated injections of steroids result in 50% of patients becoming resistant to them. In 2019, the USFDA approved Incyte Corporations’s Ruxolitinib (Jakafi), an oral JAK/STAT inhibitor, to treat patients affected by steroid-refractory acute GVHD in adult and pediatric patients. The approval was based on positive results from the Phase 2 REACH 1 trial, and Ruxolitinib became the first drug approved for the indication.

On December 5th, the company presented detailed positive results from the pivotal Phase 3 REACH3 trial at the 62nd American Society of Hematology Annual Meeting & Exposition (ASH 2020). According to the presenter, Dr. Robert Zeiser, University Hospital Freiburg, Ruxolitinib is the first agent to demonstrate superior efficacy to best available treatments in the very first large scale controlled Phase 3 trial of patients with steroid-refractory cGVHD.

“The results from this large, randomized study further emphasize the role Jakafi can play as a meaningful option for patients with chronic GVHD, for whom new treatments are urgently needed,” said Peter Langmuir, M.D., Group Vice President, Oncology Targeted Therapies, Incyte. “These data are important for patients living with GVHD and their physicians as they represent the continued success of Jakafi in the chronic form of the disease, a historically difficult-to-treat condition.”


Key Phase 3 Trial Results

The trial sponsored by Incyte and Novartis tested Ruxolitinib on four parameters, which includes one primary endpoint of overall response rate and three secondary endpoints of failure-free survival, patient-reported symptoms, and best overall response rate. Ruxolitinib showed an overall response rate (complete responses and partial responses) of 49.7% compared to 25.6% seen for best available treatment (BAT) at the end of the 24th week.

Additionally, Ruxolitinib could prolong the earliest recurrence of the underlying disease as determined through failure-free survival analysis and simultaneously showed greater symptom improvement (24% for RUX v.s 11% for BAT) as measured by modified Lee Symptom Score (mLSS). The best overall response, which includes the occurrence of stable diseases, progressive diseases in addition to complete and partial responses, was 76.4% in the drug-treated arm as compared to 60.4% in the best available treatment arm.

The safety data were comparable between the two arms; however, the occurrence of adverse events (AEs) was always slightly higher in the Ruxolitinib treatment group. The most common AEs observed in the Ruxolitinib vs. BAT arms in the trial were anemia (29% v.s 13%), hypertension (16% v.s 13%), and pyrexia (16% v.s 9%), and the mortality rates were similar across the two arms. However, deaths reported in the Ruxolitinib arm vs. BAT arms due to cGVHD were slightly higher.

A common problem with the compromised immune system is catching an infection. A higher percentage of patients treated with Ruxolitinib (64%) experienced viral, fungal, or bacterial infections than BAT (56%). This difference in the data was mainly due to higher fungal infections than viral or bacterial in the Ruxolitinib group. Treatment discontinuations were observed in 49.7% of RUX treated patients, and 74.4% of BAT treated patients. However, more treatment discontinuations due to adverse events were observed in the Ruxolitinib group (28%) than BAT (8%), and higher discontinuations due to lack of efficacy were observed in the BAT (42.7%) group than RUX (14.5%) group.

“The damaging and sometimes deadly effects of chronic GVHD following stem cell transplant present significant treatment challenges, particularly for the nearly half of patients who do not adequately respond to steroid treatment,” said Dr. Robert Zeiser, University Hospital Freiburg, Department of Haematology, Oncology and Stem Cell Transplantation, Freiburg, Germany. “Based on the compelling REACH3 results, we now have a potential new standard of care for these patients.

By Ruchi Jhonsa, Ph.D.

Related Article: Kite Presents Yescarta’s Encouraging Long Term ZUMA-1 Trial Results at ASH2020



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