Equillium Announces Positive Topline Data from the Type B Portion of the Phase 1b EQUALISE Study of Itolizumab in Lupus Nephritis
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The announcement by Equillium, Inc. regarding the positive topline data from the Phase 1b EQUALISE study for itolizumab in lupus nephritis patients is a significant milestone for the company and its stakeholders. The reported efficacy of itolizumab, with over 80% of subjects achieving a >50% reduction in urine protein creatinine ratio (UPCR), suggests a strong clinical benefit. This is particularly relevant given the current treatment landscape for lupus nephritis, which is characterized by a limited number of therapeutic options.
From a biopharmaceutical perspective, the favorable safety and tolerability profile of itolizumab is equally important. The ability to reduce proteinuria while potentially mitigating steroid use addresses a key unmet need in lupus nephritis management. Moreover, the pharmacodynamic responses, such as the reduction of cell surface CD6 on T cells, align with the drug's proposed mechanism of action, providing further validation of its biological effects.
For investors, the decision by Ono Pharmaceutical to exercise its option to acquire itolizumab, expected in the second half of 2024, will be a critical inflection point. The data could potentially enhance Equillium's valuation and attract partnership opportunities. However, it is essential to consider the competitive landscape, including treatments like voclosporin and the need for further studies to confirm long-term outcomes and safety.
The implications of the topline data from Equillium's study are not just clinical but also economic. In the field of HEOR, the focus is on the value proposition of new treatments. Itolizumab's ability to induce rapid and deep reductions in UPCR can translate into less frequent hospitalizations, slower disease progression and improved quality of life for patients. This is important for payers and healthcare systems that are increasingly adopting value-based care models.
Moreover, the reduction in corticosteroid use could decrease the long-term side effects associated with steroids, which can lead to additional healthcare costs. If itolizumab can maintain kidney function (eGFR) and increase serum albumin while reducing reliance on steroids, it may offer a cost-effective alternative to existing therapies. However, detailed cost-effectiveness analyses will be necessary to compare itolizumab with other treatments, taking into account the drug's pricing strategy and the potential impact on healthcare resource utilization.
The topline data from the EQUALISE study suggest that itolizumab may offer a novel approach to treating lupus nephritis, a disease where the standard of care has room for improvement. The clinical research community will be interested in the depth of response and the rapidity with which it was achieved. The comparison with voclosporin's response rates from the AURORA1 study is notable, but it is important to recognize that cross-trial comparisons should be approached with caution due to differences in study design and patient populations.
As a clinical research scientist, I would emphasize the need for further investigation into the long-term safety profile of itolizumab, as the current study reports on a relatively small sample size and short follow-up period. The mention of no increased rates of infection or other adverse clinical signals is promising, but larger studies are required to confirm these findings. Additionally, the impact of itolizumab on systemic corticosteroid tapering is of interest, as this could improve patient adherence and reduce the risk of steroid-related adverse effects.
Topline data delivered to Ono Pharmaceutical, representing the first of two data sets that will trigger Ono’s option exercise decision for itolizumab
Itolizumab continues to show clinically meaningful response in highly proteinuric subjects
More than
Itolizumab demonstrated a favorable safety and tolerability profile
“Physicians want to rapidly and safely reduce the levels of proteinuria in patients with lupus nephritis, as this has been associated with improved long-term outcomes, so it is important that we saw both early and large reductions in proteinuria in this study,” said Dr. Maple Fung, chief medical officer at Equillium. “The high complete and partial response rates compare favorably to those observed in the registrational studies of voclosporin, which demonstrated an overall response rate of seventy percent at six and twelve months in the active treatment groups. These itolizumab results occurred in the setting of patients tapering their systemic corticosteroids, maintaining stable kidney function, or eGFR, and increasing serum albumin while on study.”
A total of 17 subjects were enrolled in the study, with 16 subjects analyzed as completing through Week 36 (12 weeks following the final dose, or their end of study (EOS) visit). Based on published guidelines for the management of lupus nephritis from the European League Against Rheumatism (EULAR) and European Renal Association-European Dialysis and Transplant Association (ERA-EDTA), clinical activity assessments in this study are focused on the change in UPCR from baseline; proportion of apLN subjects with a complete response (CR), defined as
Key topline data from the Type B portion of the EQUALISE study in lupus nephritis:
- Subjects were highly proteinuric: baseline mean UPCR of 4.9 g/g.
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Percent reduction from baseline in median spot UPCR is ~
73% . -
Best clinical response observed by week 36 or their EOS visit:
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6 of 16 (
37.5% ) subjects achieved CR (UPCR < 0.7 g/g) -
Additional 7 of 16 (
43.8% ) subjects achieved PR (UPCR >50% reduction)
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6 of 16 (
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There was a greater overall response rate (ORR) achieved in patients receiving itolizumab by 12 and 28 weeks than expected compared to the ORR in patients receiving standard of care alone using data generated from the Accelerating Medicines Partnership® (AMP) Lupus Network. Results are comparable to those observed in the Phase 3 AURORA1 study of voclosporin (ORR
70% at 6 and 12 months in active treatment). -
Consistent with the decline in UPCR overtime, subjects were able to taper their systemic corticosteroids over the course of the study with >
80% reduction by Week 24. - Itolizumab induced consistent pharmacodynamic responses in patients reducing the levels of cell surface CD6 on T cells, which is known to reduce T cell activity.
- Itolizumab treatment (over 6 months) was also associated with reductions in absolute lymphocyte counts (ALC), another known pharmacodynamic effect.
- As noted in other studies of drugs whose mechanism leads to reductions in ALC, such as the S1P modulators, the reduction in ALC observed here was not associated with increased rates of infection or other adverse clinical signals.
- The majority of TEAEs were assessed as mild (Grade 1) or moderate (Grade 2) in severity, with the two most common TEAEs being lymphopenia and peripheral edema. Two subjects had at least one serious adverse event, none of which were related to study treatment.
About Systemic Lupus Erythematosus (SLE) & Lupus Nephritis (LN)
SLE is an autoimmune disease in which the immune system attacks its own tissues, causing widespread inflammation and tissue damage in the affected organs. It can affect the joints, skin, brain, lungs, kidneys, and blood vessels. LN is a serious complication of SLE, occurring in approximately
About the EQUALISE Study
The EQUALISE study was a two-part Phase 1b open-label proof-of-concept study of itolizumab in patients with SLE and LN. The Type A portion of the study was a multiple ascending-dose clinical study evaluating the safety and tolerability of subcutaneous delivery of itolizumab over a two-week treatment period in 35 patients with SLE. The Type B portion of the study evaluated the safety, tolerability and clinical activity of subcutaneous delivery of itolizumab dosed at 1.6 mg/kg every two weeks over a 24-week treatment period, with follow up out to 36 weeks, in patients with active proliferative LN. Patients in the Type B portion of the study must have presented with greater than 1 gram of proteinuria and had a recent kidney biopsy showing ISN/RPS class III or IV apLN to be eligible for the study. Consistent with standard of care, patients on study also received 2-3 g/day of mycophenolate mofetil/mycophenolic acid (MMF/MPA), and patients may have received pulse systemic corticosteroids that were rapidly tapered.
About Itolizumab
Itolizumab is a clinical-stage, first-in-class anti-CD6 monoclonal antibody that selectively targets the CD6-ALCAM signaling pathway to selectively 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 the following novel first-in-class immunomodulatory assets and product platform targeting immuno-inflammatory pathways. EQ101: a selective tri-specific cytokine inhibitor targeting IL-2, IL-9, and IL-15; currently under evaluation in a Phase 2 proof-of-concept clinical study of patients with alopecia areata being conducted in
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” 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 to deliver the results of the interim review of the EQUATOR study to Ono Pharmaceutical and the expected timeline for Ono Pharmaceutical to make its decision regarding exercising its option; plans for developing EQ101, EQ302 and itolizumab; 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; 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; Equillium’s plans and product development, including the initiation and completion of clinical studies and the reporting of data therefrom; changes in the competitive landscape; risks related to Ono’s financial condition and decision to exercise its option, if ever, to purchase itolizumab or terminate the asset purchase agreement; and uncertainties related to Equillium’s capital requirements. 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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Investor Contact
Michael Moore
Vice President, Investor Relations & Corporate Communications
619-302-4431
ir@equilliumbio.com
Source: Equillium, Inc.
