Equillium Announces Initiation of EQUATOR Phase 3 Study of Itolizumab in Acute Primary Graft-vs-Host Disease | Antibody
Equillium Announces Initiation of EQUATOR Phase 3 Study of Itolizumab in Acute Primary Graft-vs-Host Disease
Posted on Saturday, March 05, 2022 6:21 PM
Pivotal study to recruit up to 200 patients
Global study with sites expected in North America, Europe, Asia and Australia
Complete Response Primary Endpoint Assessment at Day 29
LA JOLLA, California, United States I March 04, 2022 I Equillium, Inc. (Nasdaq: EQ), a clinical-stage biotechnology company focused on developing novel therapies to treat serious autoimmune and inflammatory disorders with high unmet medical need, today announced the launch of the EQUATOR study, a pivotal Phase 3 clinical study of itolizumab in patients with acute graft versus host disease (aGVHD). The randomized, double-blind study will evaluate the efficacy and safety of itolizumab versus placebo as a first-line treatment for aGVHD in combination with corticosteroids. The primary objective of the study is to achieve early disease response, with key secondary objectives to assess durability of response, corticosteroid use, survival outcomes, and chronic incidence of GVHD . Primary endpoint assessment is day 29 complete response rate (CR), with key secondary endpoints day 29 overall response rate (ORR) and day 29 CR rate durability 29 to day 99.
“The initiation of this pivotal study marks an important milestone for Equillium in evaluating the potential of itolizumab as a life-changing advance for patients with acute GVHD,” said Bruce Steel, Chief Executive Officer of Equillium. .. “Patients who fail to meet existing standards of care – high-dose corticosteroids – have very poor outcomes with high mortality rates. Our Phase 3 study is supported by compelling results from our EQUATE study demonstrating complete responses rapid and sustainable treatment in patients with high-risk acute GVHD Hematologists and transplant specialists have highlighted their enthusiasm for itolizumab as a potential treatment option and we are optimistic for these patients as we launch the EQUATOR study.
“Acute GVHD remains a life-threatening condition,” said John Koreth, MD, associate professor of medicine at Harvard Medical School. “In the absence of approved drugs for first-line treatment, clinicians are hungry for treatment options beyond standard high-dose systemic corticosteroids. Itolizumab demonstrated impressive complete response rates in the EQUATE study that were both rapid and durable, and compared favorably to historical data with corticosteroid therapy alone. If successful in the EQUATOR study, itolizumab could lead to the first approval of a new therapy in the first-line treatment of acute GVHD, potentially transformative in the field.
The Phase 3 EQUATOR study is supported by results generated in the EQUATE study of 25 patients with high-risk aGVHD, where CR and ORR at day 29 were 52% and 64%, respectively, at all doses confused. When evaluating the subset of patients treated within 3 days of first corticosteroid administration (n=18), the treatment window as specified in the EQUATOR Phase 3 protocol, CR, and ORR were 61% and 67%, respectively, in all dose cohorts. Responses observed were generally rapid – within 15 days – and sustained through day 29 and beyond, with 79% of responding patients maintaining CR at six months. The adverse events reported corresponded to a population of hospitalized patients at high risk of GVHD. Itolizumab treatment resulted in a dose-dependent reduction in CD6 expression on CD4+ T cells and an increase in the ratio of regulatory to effector T cells in patients, consistent with the drug’s mechanism of action.
Equillium has received FDA Fast Track Designation for itolizumab for the treatment of patients with aGVHD and FDA Orphan Drug Designations for the prevention and treatment of aGVHD.
About the EQUATOR study
The Phase 3 multicenter, randomized, double-blind, placebo-controlled study (NCT05263999) will compare the efficacy and safety of itolizumab administered intravenously versus placebo (randomized 1:1) as a treatment first-line therapy in up to 200 adult and adolescent patients with Grade III-IV aGVHD or Grade II aGVHD with lower GI involvement, in combination with high doses of corticosteroids, the current standard of care. The primary endpoint of the study is complete response rate at day 29; key secondary endpoints include overall response rate at day 29 and durability of complete response rate from day 29 to day 99.
According to the study protocol, patients should receive itolizumab within 3 days of the first high-dose corticosteroid administration with a treatment period of days 1 to 99 and a follow-up period of days 100 to 365. Approximately 200 eligible subjects who receive 2 mg/kg methylprednisolone or equivalent on Day 1 will be randomized in a 1:1 ratio to the following two treatment groups:
- Group A: Itolizumab, initial dose of 1.6 mg/kg followed by 6 doses of 0.8 mg/kg once every 2 weeks (q2w), plus systemic corticosteroids (100 subjects)
- Group B: Placebo, 7 doses every 2 weeks, plus systemic corticosteroids (100 subjects)
An independent data monitoring committee will regularly review the safety data, and an interim analysis is planned after approximately 100 subjects complete the Day 29 assessments for futility and efficacy.
About Graft versus Host Disease (GVHD)
GVHD is a multisystem disease that is a common complication of allogeneic hematopoietic stem cell (allo-GCSH) transplants caused by the transplanted immune system recognizing and attacking the recipient’s body. Symptoms of GVHD include rash, itching, skin discoloration, nausea, vomiting, diarrhea, and jaundice, as well as dryness and irritation of the eyes.
GVHD is the leading cause of non-relapse mortality in cancer patients receiving allo-HSCT, and its risk limits the number and type of patients receiving HSCT. GVHD causes high morbidity and mortality, with a five-year survival of approximately 53% in patients who respond to corticosteroid treatment and up to 95% mortality in patients who do not respond to corticosteroids. There are no approved treatments for first-line aGVHD. The published literature (MacMillan et al., 2015) describes background response rates to high-dose corticosteroid administration in severe high-risk patients as 43% overall response and 27% complete response.
Itolizumab is a first-in-class, clinical-stage anti-CD6 monoclonal antibody that selectively targets the CD6-ALCAM pathway. This pathway plays a central role in modulating the activity and trafficking of T lymphocytes which lead to a number of immuno-inflammatory diseases. Equillium acquired the rights to itolizumab through an exclusive partnership with Biocon Limited.
Equillium is a clinical-stage biotechnology company that leverages a deep understanding of immunobiology to develop novel therapies to treat serious autoimmune and inflammatory disorders with high unmet medical need. The Company’s pipeline includes the following novel immunomodulatory actives targeting immune-inflammatory pathways. Itolizumab, a first-in-class monoclonal antibody that targets the CD6-ALCAM signaling pathway that plays a central role in modulating effector T cells, is currently in a Phase 3 study for patients with acute graft versus host disease (aGVHD) and is being studied in a Phase 1b study for patients with lupus/lupus nephritis. BNZ-1, a first-in-class trispecific cytokine inhibitor that selectively targets IL-2, IL-9 and IL-15, is Phase 2 ready and expected to begin enrolling patients in a study in alopecia areata in the second half of 2022. BNZ-2, a bispecific cytokine inhibitor that selectively targets IL-15 and IL-21, is ready for clinical development and is expected to begin enrolling patients in a phase 1 study to enroll patients with celiac disease in the second half of 2022. For more information, visit www.equilliumbio.com.
THE SOURCE: Equillium