▎WuXi AppTec Content Team Report

Today (June 13), Novartis announced that itsJAK Inhibitor Ruxolitinib Phosphate TabletsApproved by the National Medical Products Administration (NMPA) of China for a new indication, used for the treatment ofPatients aged 12 years and older with chronic graft-versus-host disease (cGVHD) who have had an inadequate response to corticosteroids or other systemic treatments。

Prior to this, ruxolitinib was approved by the NMPA in 2023 for the treatment of patients with inadequate response to glucocorticoids or other systemic therapies.Patients 12 years and older with acute GVHD (aGVHD), and was approved in China in 2017 for use in adult patients with intermediate or high-risk primary myelofibrosis (PMF), post-polycythemia vera myelofibrosis (PPV-MF), or post-essential thrombocythemia myelofibrosis (PET-MF) to treat disease-related splenomegaly or disease-related symptoms.

Hematopoietic stem cell transplantation (HSCT) represents a new hope for many patients with hematological diseases. However, 30% to 70% of patients receiving allogeneic hematopoietic stem cell transplantation face the threat of chronic graft-versus-host disease (cGVHD). cGVHD can affect one or more organs, primarily including the skin, eyes, mouth, liver, gastrointestinal tract, and lungs. It presents features of autoimmune vascular collagen disease characterized by multi-organ damage such as scleroderma, bronchiolitis obliterans, fibrosis of the liver and skin, and deposition of alloantibodies in target organs. This complication is a significant cause of late non-relapse mortality after allo-HSCT and can severely impact patients' social functioning and quality of life.

According to literature reports, glucocorticoids remain the first-line treatment for cGVHD; however, their efficacy rate is only 50%-60%, with some patients progressing to steroid-refractory cGVHD (SR-cGVHD). These patients have a poor prognosis, and long-term use of glucocorticoids can lead to adverse effects such as infections and osteoporosis, increasing the risk of poor outcomes. There remains a significant unmet medical need for SR-cGVHD patients in clinical practice.

The mechanism of cGVHD is complex, with the main pathophysiological process being immune-inflammatory response. The common pathological change is fibrosis. Janus kinase 1 and 2 (JAK1-JAK2) signaling plays an important role in the steps leading to inflammation and tissue damage. Ruxolitinib is a JAK1/2 inhibitor.The incidence of cGVHD can be reduced by inhibiting the proliferation of donor T cells, the production of inflammatory cytokines, and the function and activity of Tregs.. In addition, preclinical studies on systemic sclerosis have shown,Ruxolitinib can prevent or improve skin fibrosis and pulmonary fibrosis, with anti-fibrotic properties.。

According to the Novartis press release, a randomized, open-label, Phase 3 clinical study (REACH3) compared ruxolitinib with the current Best Available Therapy (BAT) for treatment.Patients (≥12 years old) with moderate to severe glucocorticoid-refractory or -dependent cGVHD after allogeneic stem cell transplantationThe efficacy of Ruxolitinib was shown to be superior to BAT.

At week 24, the ruxolitinib treatment groupThe overall response rate was significantly higher than that of the BAT group (49.7% vs 25.6%), with an even higher best overall response rate (76.4% vs 60.4%).。In terms of efficacy across different affected organs, the response rate for individual organs in the ruxolitinib treatment group was higher than that in the control group, including the lower gastrointestinal tract, esophagus, oral cavity, skin, upper gastrointestinal tract, joints and fascia, eyes, liver, and lungs.

In addition, patients in the ruxolitinib groupSymptom relief rate was higher than in the control group (24.2% vs 11.0%).. According to the comparison results of quality of life scale scores reported by patients,At week 24, 72.6% and 54.6% of patients in the ruxolitinib treatment group and BAT group, respectively, were asymptomatic or had mild symptoms.The 3-year follow-up results showed,The median failure-free survival in the ruxolitinib group was longer than that in the BAT group (38.4 months vs 5.7 months), with 12-month failure-free survival rates of 64.0% and 28.8%, respectively.

In terms of safety, the incidence of grade 3 or higher adverse events, as well as the incidence of cytomegalovirus infection and reactivation, were similar between the two groups. No new safety events were observed in the ruxolitinib treatment group.