Equillium Announces Results of the Phase 3 EQUATOR Study of Itolizumab in First-Line Treatment of Patients with Acute Graft-Versus-Host Disease
Treatment with itolizumab did not improve complete or overall response rates at Day 29
Itolizumab achieved statistical significance in multiple secondary endpoints demonstrating compelling clinical benefit in longer-term outcomes, including complete response at Day 99, duration of complete response and failure-free survival
Breakthrough Therapy designation and meeting requests to discuss potential for Accelerated Approval submitted to FDA, feedback expected during May 2025
Management will host a conference call and webcast today at 8:30 am ET
“While we did not observe improvements in Day 29 outcomes, itolizumab demonstrated compelling clinical results in several important longer-term outcomes, conferring potential patient benefit where there are no approved therapies,” said Bruce Steel, chief executive officer at Equillium. “Based on these data and prior FDA guidance, we have filed for Breakthrough Therapy designation and have been granted a meeting to discuss the potential for Accelerated Approval of itolizumab for first-line treatment of aGVHD, a rare disease where one-year mortality exceeds 40 percent and itolizumab has already received Orphan Drug and Fast Track designations. We expect feedback from the FDA during May and, if positive, we would plan to submit a biologics license application during the first half of 2026.”
“The longer-term outcomes are important,” said Dr. John Koreth, Professor of Medicine, Dana-Farber Cancer Institute, Harvard Medical School. “There are no approvals in first-line therapy for aGVHD, and no drug candidates have been able to demonstrate efficacy beyond four weeks. To demonstrate statistical significance in pre-specified endpoints of duration of complete response and failure-free survival, compared to standard of care therapy, is clinically meaningful.”
The Phase 3 EQUATOR study in first-line aGVHD demonstrated a favorable safety and tolerability profile, and clinically meaningful longer-term outcomes. There was no meaningful difference in CR or ORR, the primary endpoint and a key secondary endpoint of the study (respectively), at Day 29 between patients treated with itolizumab and placebo, but statistical significance was achieved in several critically important secondary endpoints demonstrating improvement in longer term outcomes:
- Statistical significance in duration of CR favoring itolizumab, with a median 336 days vs. 72 days, p-value 0.017.
- Statistical significance in failure-free survival favoring itolizumab, with a median 154 vs. 70 days, p-value 0.043.
-
Statistical significance in complete response at Day 99 favoring itolizumab, with 35 (
44.9% ) vs. 22 (28.6% ) patients, p-value 0.035. -
Positive trend in overall survival favoring itolizumab, with mortality of 19 (
24.4% ) vs. 25 (32.5% ) patients. - Steroid tapering and rates of primary disease relapse and chronic GVHD were similar for both treatment arms.
Summary of Efficacy Results from the EQUATOR Study |
|||
Endpoint, n (%) |
Itolizumab
|
Placebo
|
p-value |
CR at Day 29 (ITT), n (%)
|
34 (43.0) |
38 (48.1) |
NSS |
ORR at Day 29 (ITT), n (%)
|
49 (62.0)
|
43 (54.4)
|
NSS |
Durable CR at Day 99 (ITT)#, n (%)
|
23 (29.1) |
13 (16.5) |
NSS |
Durable CR at Day 99 (of Day 29 CRs) (ITT)#*, n (%) |
23 (67.6) |
13 (34.2) |
0.005 |
CR at Day 99 (mITT)*, n (%) |
35 (44.9) |
22 (28.6) |
0.035 |
Duration of CR (mITT), median days |
336 days |
72 days |
0.017 |
Failure Free Survival (mITT) |
|||
Kaplan-Meier estimate of rate at Day 365, % Median days |
154 days |
70 days |
0.043 |
Overall Survival (mITT) |
|
|
|
Kaplan-Meier estimate of rate at Day 365, % Deaths, n |
19 |
25 |
NSS |
Data based on 11 December 2024 database lock, unless otherwise noted, and subject to change. #Estimate as of 12 February 2025 with one subject pending final analysis; *Post-hoc analysis. Analyses were pre-specified in the Statistical Analysis Plan, unless indicated as a post-hoc analysis. Abbreviations: ITT, intent-to-treat; mITT, modified intent-to-treat (subjects who received at least one dose; removes three patients that did not receive any study treatment); CR, complete response; NSS, not statistically significant; VGPR, very good partial response; PR, partial response |
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The safety profile observed in the EQUATOR study was consistent with that observed in previously reported studies of itolizumab, and itolizumab did not increase the risk of clinical sequelae, including rates of infection and sepsis.
Overall Summary of Treatment-Emergent Adverse Events (Safety Population / mITT) |
|||
Event, n (%) |
Itolizumab
|
Placebo
|
Total
|
Subjects with any TEAE |
77 (98.7) |
74 (96.1) |
151 (97.4) |
Subjects with TEAE leading to study drug discontinuation |
10 (12.8) |
3 (3.9) |
13 (8.4) |
Subjects with TESAEs |
45 (57.7) |
47 (61.0) |
92 (59.4) |
Infections and infestations TESAEs |
22 (28.2) |
29 (37.7) |
51 (32.9) |
Treatment-related TESAEs |
5 (6.4) |
3 (3.9) |
8 (5.2) |
Subjects with TEAE leading to death |
18 (23.1) |
25 (32.5) |
43 (27.7) |
Treatment-related TEAE leading to death |
0 (0) |
0 (0) |
0 (0) |
Most Common TESAEs |
|
|
|
Sepsis |
4 (5.1) |
14 (18.2) |
18 (11.6) |
Respiratory failure |
3 (3.8) |
4 (5.2) |
7 (4.5) |
Pneumonia |
3 (3.8) |
3 (3.9) |
6 (3.9) |
Septic shock |
2 (2.6) |
4 (5.2) |
6 (3.9) |
Data based on 11 December 2024 database lock, unless otherwise noted, and subject to change. Abbreviations: mITT, modified intent-to-treat (subjects who received at least one dose; removes three patients from ITT that did not receive any study treatment); TEAE, treatment-emergent adverse event; TESAE treatment-emergent serious adverse event |
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Webcast and Conference Call
Management will host a conference call accompanied by a slide presentation to provide an overview of the data from the Phase 3 EQUATOR study in first-line aGVHD, for analysts and institutional investors, at 8:30 am ET today, March 27, 2025. To access the call, please dial (800) 715-9871 or (646) 307-1963 for international callers, and if needed provide conference ID number 2574379. A live webcast of the call will also be available on the company’s Investor Relations page. The webcast will be archived for 180 days.
About Graft-Versus-Host Disease (GVHD)
GVHD is a multisystem disorder that is a common complication of allogeneic hematopoietic stem cell transplants (allo-HSCT) 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 eye dryness and irritation.
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 results in high morbidity and mortality, with one year survival as low as
About the EQUATOR Study
The Phase 3, randomized, double-blind, placebo-controlled multicenter study (NCT05263999) compared the efficacy and safety of intravenous administered itolizumab versus placebo (randomized 1:1) as a first-line therapy in 158 adult and adolescent patients with Grade III-IV aGVHD, or Grade II aGVHD with lower gastrointestinal involvement, in combination with high doses of corticosteroids, the current standard of care. The primary study endpoint was complete response rate (CR) at Day 29; key secondary endpoints included overall response rate (ORR) at Day 29 and rate of durable CR from Day 29 through Day 99. Additional secondary outcomes included CR at Day 99, duration of CR, failure free survival, and overall survival.
Per the study protocol, patients received itolizumab within 3-days of the first administration of high-dose corticosteroids with a treatment period from Days 1-99, and a follow-up period from Days 100-365. Subjects received 2 mg/kg methylprednisolone or equivalent on Day 1 and were randomized in a 1:1 ratio to the following two treatment groups:
- Group A: Itolizumab, 1.6 mg/kg initial dose followed by 6 doses of 0.8 mg/kg once every 2 weeks (q2w), plus systemic corticosteroids (79 subjects)
- Group B: Placebo, 7 doses every other week, plus systemic corticosteroids (79 subjects)
The EQUATOR study remains ongoing with all patients having completed dosing, and 30 patients in the follow-up period per protocol. An independent data monitoring committee oversees the study and regularly reviews safety data.
About Itolizumab
Itolizumab is a clinical-stage, first-in-class anti-CD6 monoclonal antibody that selectively targets the CD6-ALCAM signaling pathway to downregulate pathogenic T effector cells while preserving T regulatory cells critical for maintaining a balanced immune response. This pathway plays a central role in modulating the activity and trafficking of T cells that drive a number of immuno-inflammatory diseases.
About Equillium
Equillium is a clinical-stage biotechnology company leveraging a deep understanding of immunobiology to develop novel therapeutics to treat severe autoimmune and inflammatory disorders with high unmet medical need. The company’s pipeline consists of several novel immunomodulatory assets and product platform targeting immuno-inflammatory pathways.
For more information, visit www.equilliumbio.com.
Forward Looking Statements
Statements contained in this press release regarding matters that are not historical facts are “forward-looking Statements” within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements may be identified by the use of words such as “anticipate”, “believe”, “could”, “continue”, “expect”, “estimate”, “may”, “plan”, “outlook”, “future”, “potential” and “project” and other similar expressions that predict or indicate future events or trends or that are not statements of historical matters. These statements include, but are not limited to, statements regarding Equillium’s plans and strategies with respect to developing itolizumab (EQ001), the encouraging impact of the positive data in the context of Equillium’s Phase 3 EQUATOR study in aGVHD, Equillium’s ability to raise additional capital to support filing of a biologics license application, the expected timing of FDA feedback, and the potential benefits of Equillium’s product candidates. Because such statements are subject to risks and uncertainties, many of which are outside of Equillium’s control, actual results may differ materially from those expressed or implied by such forward-looking statements. Risks that contribute to the uncertain nature of the forward-looking statements include: Equillium’s ability to execute its plans and strategies; Equillium’s ability to continue as a going concern; risks related to performing clinical and pre-clinical studies; whether the results from clinical and pre-clinical studies will validate and support the safety and efficacy of Equillium’s product candidates; whether the topline results from the EQUATOR study will support accelerated approval and Breakthrough Therapy designation; changes in the competitive landscape; Equillium’s ability to raise additional funding; and changes in Equillium’s strategic plans. These and other risks and uncertainties are described more fully under the caption "Risk Factors" and elsewhere in Equillium's filings and reports, which may be accessed for free by visiting the Securities and Exchange Commission’s website and on Equillium’s website under the heading “Investors.” Investors should take such risks into account and should not rely on forward-looking statements when making investment decisions. All forward-looking statements contained in this press release speak only as of the date on which they were made. Equillium undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made, except as required by law.
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Corporate Contact
Michael Moore
Vice President, Investor Relations & Corporate Communications
619-302-4431
ir@equilliumbio.com
Source: Equillium, Inc.
