FDA Approves Incyte’s Jakafi for Chronic Graft-Versus-Host Disease

Delaware-based Incyte Corporation is on a roll, winning back-to-back FDA approvals for its JAK inhibitor, ruxolitinib, for two different indications. On September 22nd, it announced that the agency has approved Jakafi (ruxolitinib) for the treatment of chronic graft-versus-host disease (GVHD) after the failure of one or two lines of systemic therapy in adults and pediatric patients 12 years and older.

Just a day earlier, the company notched a regulatory win for Opzelura (ruxolitinib) cream for treating atopic dermatitis in non-immunocompromised patients of age 12 and above. 

“GVHD is the leading cause of morbidity and mortality in patients following an allogeneic stem cell transplant, yet there historically have been limited treatment options available beyond first-line systemic therapies,” stated Steven Stein, M.D., CMO of Incyte.

“Incyte is proud to have contributed to the overall scientific understanding of GVHD through our REACH program, which has led to important treatment advances on behalf of patients and the medical community, including today’s approval of Jakafi for certain people who develop chronic GVHD.”

Chronic Graft Versus Host Disease

Cancer patients lose a lot of bone marrow cells during treatments like chemotherapy or radiation. Therefore leukemic and lymphoma patients often undergo stem cell transplantation to rejuvenate their immune cells. This involves receiving stem cells from a donor or donated umbilical cord blood.

However, during this process, the donor’s T cells can render the patient’s healthy cells as a foreign body and begin to attack and kill them. This condition, called chronic graft versus host disease (cGVHD), affects about 30% to 70% of patients who undergo this procedure, resulting in nonrelapse mortality and morbidity.

“In the US, there are over 14,000 people living with chronic GVHD, many of whom face significant complications that may impair daily activities and linger for years,” said Susan Stewart, Executive Director, BMT InfoNet. “The approval of Jakafi is an exciting development for the GVHD community and an important step forward in the treatment of a disease with few options.”

Systemic steroids are the standard first-line therapy for cGVHD, but repeated injections often result in resistance in close to 50% of patients.

In 2019, following the positive results from the Phase 2 REACH 1 trial, Incyte’s Jakafi, an oral JAK/STAT inhibitor, became the first FDA-approved drug to treat patients affected by steroid-refractory acute GVHD in adult and pediatric patients.

The latest approval for cGVHD marks the fourth FDA-approved indication for Jakafi. Although this is a remarkable milestone, analysts say it will have a minimal effect on the company due to the off-label use of such agents for treating cGVHD even before FDA approval.

Positive Phase 3 Trial Data

“Nearly half of the people who develop chronic GVHD do not respond adequately to steroids – the current standard of care – making this life-threatening condition particularly challenging to treat,” said principal trial investigator, Dr. Robert Zeiser, University Medical Center Freiburg, Department of Hematology, Oncology and Stem Cell Transplantation, Freiburg, Germany

The FDA approval is all thanks to Jakafi’s performance in the Phase 3 REACH3 study, which pitted the drug against the best available therapy (BAT) to treat steroid-refractory chronic GVHD after allogeneic stem cell transplantation. The drug was evaluated on four parameters—a primary endpoint of overall response rate (ORR) and three secondary endpoints of failure-free survival, patient-reported symptoms, and best overall response rate.

Results showed that Jakafi met the primary endpoint by registering an ORR of 49.7% compared to 25.6% for BAT (P<0.0001) at Week 24.  Besides, the drug could prolong the earliest recurrence of the underlying disease as determined through failure-free survival analysis and simultaneously showed greater symptom improvement (24.2% vs. 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 BAT arm. The full results of the trial were published in the New England Journal of Medicine last July.

“In this clinical trial, treatment with Jakafi demonstrated significantly improved outcomes across a range of efficacy measures compared to best available therapy. This approval represents a significant advancement in the treatment of appropriate patients with chronic GVHD – for both the patients who face a poor prognosis and the healthcare providers who struggle to effectively treat them,” Dr. Zeiser added.

Author

Rajaneesh K. Gopinath