Phase 3 Trial of First-line Treatment for Acute GVHD is Underway

The 200-patient trial will test whether adding a monoclonal antibody called itolizumab to high doses of corticosteroids will improve outcomes for patients who develop acute graft-versus-host-disease after a stem cell transplant.

The first-line treatment for acute graft-versus-host-disease (GVHD) is currently treated high doses of corticosteroids. Executives of a Southern California biotech company think they have a monoclonal antibody that, when used with high doses of corticosteroids, will markedly improve outcomes for patients with acute GVHD.

Equillium Inc. in La Jolla, California, recently announced that it was a launching a 200-patient, phase 3 trial of the monoclonal antibody, itolizumab. Patients are to be randomized to regimen of either itolizumab and high doses of corticosteroids or a placebo and high doses of corticosteroids. The primary endpoint is a complete response after 29 days.

Jakafi (ruxolitinib)and Rezurock (belumosudil) are approved as treatments for steroid-refractory acute GVHD but not as first-line treatments.

““By the time patients are truly refractory to steroids, the disease gets even more difficult to treat, so we thought the best opportunity for our drug to show a benefit was in the first-line setting,” Bruce Steel, the CEO of Equillium, said in a recent interview with Managed Healthcare Executive.®

GVHD is a side effect experienced by patients with blood cancers such as acute myeloid leukemia who have received a stem cell transplant from another person. The donor stem cells reconstitute patients’ immune system after they have received cancer treatment that targets the cancerous stem cells and wipes out their immune system in the process. But sometimes the new, “grafted” immune system attacks the “host” — other tissues in the body, especially those in the skin, liver and gastrointestinal tract.

“It is kind of like organ transplant rejection in reverse,” said Steel.

Steel said there are between 10,000 and 12,000 stem cell transplants conducted in the U.S. every year and that roughly half of patients develop acute GVHD. About half of the patients with acute GVHD, or about 3,000 patients, are not treated successfully with corticosteroids,

Itolizumab targets the CD6-ALCAM pathway that regulates a type of T cell that is important in GVHD and other conditions characterized by a dysregulated immune system. Equillium bills itolizumab as a pioneering, “first in class,” anti-CD6 monoclonal antibody. Steel said there are positive results for itolizumab as a treatment for lupus and asthma.

““We have a bolus of data that supports our thesis that we have potentially very compelling therapeutic on our hands,” Steel said

Equillium licensed itolizumab from Biocon, a large Indian pharmaceutical company. Equillium has rights to the monoclonal antibody for sales in the U.S., Canada, Australia and New Zealand, Steel said, while Biocon has retained the rights to sell it elsewhere. Steel said Biocon will manufacture the monoclonal antibody for Equillium.

The launching of the phase 3 trial, which Equillium is calling EQUATOR, comes after Equillium reported positive results from a 25-patient study dubbed EQUATE.

In the March 4 news release about the launching of the phase 3 trial, Equillium said the 52% of the patients in the EQUATE trial had a complete response after 29 days. Among the 18 patients who were treated with monoclonal antibody within three days after their first corticosteroid treatment, the complete response rate was 61%, according to the press release, and the design of the phase 3 EQUATE trial specifies that patients should receive itolizumab (or the placebo if they are randomized to the placebo group) within three days of receiving the corticosteroid treatment.

Steel said researchers at Dana-Farber Cancer Institute in Boston used itolizumab on experimental basis decades ago. In those studies, the monoclonal antibody was used to treat stem cells outside the body that were then transfused back into the patient that they were taken from (an autologous stem cell transplant instead of an allogeneic one). The results were promising, he said, but scaling up the approach so it could be done outside a research context wasn’t practical.