Robert Zeiser, MD from the University Medical Center Freiburg, speaks about Incyte Announces Acceptance and Priority Review of sNDA for Jakafi® (ruxolitinib) as a Treatment for Patients with Chronic Graft-Versus-Host Disease.
(BUSINESS WIRE)—WILMINGTON, Del.— The supplemental New Drug Application (sNDA) for ruxolitinib (Jakafi®) for the treatment of steroid-refractory chronic graft-versus-host disease (GVHD) in adult and pediatric patients 12 years and older has been approved for Priority Review by the US Food and Drug Administration (FDA).
The sNDA is focused on the findings of the REACH3 review, which compared ruxolitinib to best available therapy (BAT) in patients with steroid-refractory chronic GVHD. Patients treated with ruxolitinib had a substantially higher overall response rate (ORR) than patients treated with BAT at Week 24, the primary endpoint, in the REACH3 trial, which was recently presented at the 62nd American Society of Hematology (ASH) Annual Meeting & Exposition (49.7% vs. 25.6 percent; p0.0001). At Week 24, ruxolitinib was associated with a longer median failure-free survival (FFS) than BAT (not achieved vs. 5.7 months; danger ratio (HR), 0.370; p0.0001), as well as greater symptom improvement on the updated Lee Symptom Scale (mLSS) (24.2 percent vs. 11.0 percent; odds ratio (OR), 2.62; p=0.0011). The best ORR for ruxolitinib-treated patients was 76.4 percent. There were no new safety signals, and adverse effects were consistent with ruxolitinib’s established safety profile.
After an allogeneic stem cell transplant (the transfer of stem cells from a donor), GVHD is a disease in which the donated cells cause an immune reaction and invade the transplant recipient’s organs, resulting in substantial morbidity and mortality. Acute GVHD, which occurs within 100 days of transplantation, and chronic GVHD, which occurs after 100 days of transplantation, are the two main types of GVHD. Both types can affect the skin, gastrointestinal (digestive) tract, and liver, among other organ systems.
Priority Review is given by the FDA to medicines that could provide a substantial improvement in care where none currently exists. This designation reduces the review period to six months, as opposed to the standard review period of ten months. The target action date for Jakafi in steroid-refractory chronic GVHD under the Prescription Drug User Fee Act (PDUFA) is June 22, 2021.
The sNDA is also being reviewed as part of the Project Orbis program, a U.S. FDA Oncology Center of Excellence initiative that offers a mechanism for simultaneous submission and evaluation of oncology drugs by international regulatory agencies. Canada, Australia, Switzerland, Brazil, and the United Kingdom are among the countries that have signed up for this application.
The US Food and Drug Administration approved Jakafi in 2019 for the treatment of steroid-refractory acute GVHD in adults and children aged 12 and up2.
REACH3 (NCT03112603) is a randomized, open-label, multicenter Phase 3 study sponsored by Novartis and performed in conjunction with and co-funded by Incyte to assess the safety and efficacy of ruxolitinib in patients with steroid-refractory chronic GVHD compared to best available therapy.
At Week 24 (i.e., Cycle 7, Day 1), the primary endpoint is the overall response rate (ORR), which is characterized as the percentage of participants who show a complete or partial response. Failure-free survival (FFS) and improvement in the updated Lee Symptom Scale (mLSS) score at Week 24 are important secondary endpoints. Best overall response (BOR), length of response (DoR), overall survival (OS), and protection are some of the secondary endpoints. Visit https://clinicaltrials.gov/ct2/show/NCT03112603 for more details on the research.
The randomized pivotal Phase 3 REACH2 and REACH3 trials, performed in conjunction with Novartis, are part of the REACH clinical trial program evaluating ruxolitinib in patients with steroid-refractory GVHD.
The Incyte-sponsored REACH1 study, a prospective, open-label, single-cohort, multicenter, pivotal Phase 2 trial examining Jakafi in conjunction with corticosteroids in patients with steroid-refractory grade II-IV acute GVHD (NCT02953678), kicked off the REACH program. Visit https://clinicaltrials.gov/show/NCT02953678 for more information about the research, including trial details.