The Food and Drug Administration (FDA) has accepted for Priority Review the supplemental New Drug Application (sNDA) for ruxolitinib for the treatment of steroid-refractory chronic graft-vs-host disease (GVHD) in patients 12 years of age and older.
The sNDA submission is based on data from the multicenter, randomized, open-label phase 3 REACH3 study (ClinicalTrials.gov: NCT03112603), which assessed the efficacy and safety of ruxolitinib, a Janus kinas (JAK)1/JAK2 inhibitor, in patients aged 12 years and older with steroid-refractory chronic GVHD. Patients were randomly assigned to receive either ruxolitinib or best available therapy (BAT). The primary end point was overall response rate (ORR) at week 24, defined as the percentage of patients demonstrating a complete or partial response.
Results showed an ORR of 49.7% in the ruxolitinib arm vs 25.6% for the BAT group (P <.0001) at week 24. Moreover, ruxolitinib met key secondary end points achieving statistically significant and clinically meaningful improvements for the following, compared with BAT, respectively:
- Median failure-free survival (FFS; defined as time to the earliest recurrence of the underlying disease, start of new systemic treatment for chronic GVHD, or death): Not reached vs 5.7 months (hazard ratio [HR] 0.37; 95% CI, 0.27-0.51; P <.0001);
- Modified Lee Symptom Score (mLSS; as measured by the rate of responders who achieved a reduction of greater than or equal to 7 points of total symptom score): 24.2% vs 11.0% (odds ratio [OR] 2.62; P =.0011);
- Best ORR, defined as any response up to week 24: 76.4% vs 60.4% (OR 2.17; 95% CI, 1.34-3.52);
- Median duration of response (DOR): Not reached vs 6.2 months.
As for safety, there were no new safety signals observed in the study. The most common adverse events reported in the ruxolitinib and BAT arms, respectively, were anemia (29.1% vs 12.7%), hypertension (15.8% vs 12.7%) and pyrexia (15.8% vs 9.5%). The rate of discontinuations due to adverse events were 16.4% and 7% for ruxolitinib and BAT arms, respectively. The ruxolitinib arm also reported slightly higher deaths primarily due to chronic GVHD.
A Prescription Drug User Fee Act (PDUFA) target date of June 22, 2021 has been set for this application.
Ruxolitinib is marketed under the trade name Jakafi® and is currently indicated for the treatment of steroid-refractory acute GVHD, myelofibrosis (MF), and polycythemia vera.
- Incyte announces acceptance and Priority Review of sNDA for Jakafi® (ruxolitinib) as a treatment for patients with chronic graft-versus-host disease. [press release]. Wilmington, DE: Incyte; February 22, 2021.
- Incyte announces first data from REACH3 trial showing ruxolitinib (Jakafi®) significantly improved outcomes in patients with steroid-refractory or steroid-dependent chronic graft-versus-host disease. [press release]. Wilmington, DE: Incyte; December 4, 2020.