- Zetomipzomib added to stable background therapy reduced
proteinuria by 50% or greater (ORR) in 11 of 17 patients (64.7%)
reaching end of treatment at Week 25. This benefit occurred with a
53% mean reduction of background corticosteroid use.
- ORRs increased to 94.1% at Week 29 and 88.2% at Week 37 during
the safety follow-up period with stable background therapy.
- Complete renal responses, including a urine protein to
creatinine ratio (UPCR) of 0.5 or less (CRR), were achieved in 6 of
17 patients (35.3%) at end of treatment and increased to 7 of 17
patients (41.2%) during the safety follow-up period at Weeks 29 and
37.
- Reduction in proteinuria was consistently observed with
reduction in extra-renal manifestations of SLE and improvements in
key biomarkers.
- Zetomipzomib continues to demonstrate a favorable safety and
tolerability profile, with no evidence of immunosuppression and no
new safety signals during the follow up period.
Kezar Life Sciences, Inc. (Nasdaq: KZR), a clinical-stage
biotechnology company discovering and developing breakthrough
treatments for immune-mediated and oncologic disorders, today
announced that it presented the complete data set from the MISSION
Phase 2 clinical trial evaluating zetomipzomib, a novel,
first-in-class, selective immunoproteasome inhibitor, in active
lupus nephritis (LN) at the American Society of Nephrology’s (ASN)
Kidney Week 2022 Annual Meeting in Orlando, FL.
“MISSION Phase 2 accomplished the goal of demonstrating that
zetomipzomib, a first-in-class inhibitor of the immunoproteasome,
has potent anti-inflammatory effects which result in clinically
meaningful reductions in proteinuria in patients who do not respond
fully to standard-of-care therapies. The anti-inflammatory effect
is sustained following discontinuation of zetomipzomib, consistent
with earlier data, and occurs without evidence of
immunosuppression. Based on these exciting results, we believe
zetomipzomib has the potential to be a long-term, steroid-sparing,
broad immunomodulating treatment for patients with lupus
nephritis,” said Noreen R. Henig, M.D., Kezar’s Chief Medical
Officer. “We are moving quickly to launch a multi-country
randomized placebo-controlled study to evaluate zetomipzomib in
patients with LN, as well as exploring the potential of the novel
mechanism of action in diseases such as autoimmune hepatitis and
systemic lupus erythematosus.”
The MISSION Phase 2 clinical trial was an open-label study
designed to demonstrate the responder rate of zetomipzomib in
patients with active LN. During the 24-week treatment period,
patients received 60 mg of zetomipzomib subcutaneously once weekly
(first dose of 30 mg) in addition to stable background therapy.
End-of-treatment (EOT) assessments occurred at Week 25, with
completion of the study at Week 37 (EOS). Patients in the MISSION
Phase 2 clinical trial received zetomipzomib without induction
therapy, which represents a significant difference from other
recently published clinical trials in LN. The primary efficacy
endpoint for this trial was the proportion of patients achieving an
overall renal response (ORR), measured as a 50% or greater
reduction in urine protein to creatinine ratio (UPCR) at EOT. A key
secondary efficacy endpoint was the number of patients with a
complete renal response (CRR), measured as an absolute reduction in
proteinuria values to a UPCR of 0.5 or less, with preserved renal
function (eGFR), and corticosteroid use of 10 mg or less
prednisone/prednisone equivalent and no use of prohibited
medication. Exploratory endpoints included measures of systemic
lupus erythematosus (SLE) disease activity, including Systemic
Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K),
Physician Global Assessment and Patient Global Assessment
scores.
Summary of Results from the Completed
MISSION Trial
In the MISSION Phase 2 clinical trial, 17 of 21 enrolled
patients reached end-of-treatment at Week 25 and end-of-study at
Week 37. Zetomipzomib treatment demonstrated clinically meaningful
renal responses with additional ORRs and CRRs observed during the
safety follow-up period.
- Overall Renal Responses:
- At EOT, 11 of 17 patients (64.7%) achieved an ORR measured as a
50% or greater reduction in UPCR compared to baseline, the primary
endpoint of the clinical trial.
- During the safety follow-up period, clinical responses
deepened, and ORRs increased to 16 of 17 patients (94.1%) at Week
29 and 15 of 17 patients (88.2%) at EOS.
- 12 of 17 patients (70.6%) also reached UPCR of 0.7 or less at
EOS.
- Complete Renal Responses:
- At EOT, 6 of 17 patients (35.3%) achieved a CRR, including a
UPCR of 0.5 or less, stable eGFR, daily prednisone/prednisone
equivalent dose of 10 mg or less, and no use of prohibited
medication.
- During the safety follow-up period, an additional patient
achieved a CRR, with the total CRRs increasing to 7 of 17 patients
(41.2%) at Week 29 and EOS, demonstrating a deepening renal
response throughout the 37-week trial.
- Urinary CD163, a biomarker that suggests active inflammation in
the kidney, showed a strong correlation to UPCR across all
timepoints in the study. These data indicate that patients had
active inflammation at baseline despite standard-of-care therapy
and that the addition of zetomipzomib has the potential to resolve
inflammation.
- By Week 13, 14 of 17 patients (82.4%) achieved a daily
corticosteroid dose of 10 mg or less, despite no protocol-mandated
steroid taper. Doses of background immunosuppressive agents
remained stable throughout the study, including during the 12-week
safety follow-up.
- Mean eGFR (estimated glomerular filtration rate) remained
stable from baseline to EOS.
- Key measurements of SLE disease activity were reduced and key
biomarkers of SLE improved. There was no evidence of early rebound
of inflammation following discontinuation of zetomipzomib.
- SLEDAI-2K scores reduced from a mean of 11.3 at baseline to 6.5
at EOT and 5.8 at EOS.
- Physician Global Assessment scores reduced from a mean of 57.2
at baseline to 23.9 at EOT and 16.2 at EOS.
- Patient Global Assessment scores reduced from a mean of 23.6 at
baseline to 10.7 at EOT and 6.6 at EOS.
- Of the 12 patients with abnormal levels of double-stranded DNA
antibody levels (anti-dsDNA) at baseline, 10 patients showed
improved or normalized levels of anti-dsDNA at EOT, which
improvement was maintained in 9 patients at EOS.
Safety
Zetomipzomib continued to be well-tolerated over the course of
the 37-week study, demonstrating a favorable safety and
tolerability profile. Overall, adverse events were generally
mild-to-moderate (Grade 1 or 2) and were consistent with what was
previously reported with topline data. Early terminations occurred
in 4 out of 21 patients. No opportunistic or Grade 3 infections
were reported in the trial.
Poster Presentation
Details:
Abstract Title: Zetomipzomib (KZR-616), A First-in-Class
Selective Immunoproteasome Inhibitor for the Treatment of Lupus
Nephritis: Preliminary Results from the Phase 2 MISSION Study
Session: Glomerular Diseases: Clinical, Outcomes, Trials - I
[PO1303-1] Date/Time: November 3, 2022 from 10:00 AM - 12:00
PM ET Presenter: Dr. Samir V. Parikh, MD, Associate
Professor of Medicine, Division of Nephrology, The Ohio State
University Wexner Medical Center
The MISSION poster presentation is currently available in the
“Scientific Publications” section of Kezar Life Science’s website
at www.kezarlifesciences.com.
About Zetomipzomib
Zetomipzomib (KZR-616) is a novel, first-in-class, selective
immunoproteasome inhibitor with broad therapeutic potential across
multiple autoimmune diseases. Preclinical research demonstrates
that selective immunoproteasome inhibition results in a broad
anti-inflammatory response in animal models of several autoimmune
diseases, while avoiding immunosuppression. Data generated from
Phase 1 and Phase 2 clinical trials provide evidence that
zetomipzomib exhibits a favorable safety and tolerability profile
for development in severe, chronic autoimmune diseases.
About Lupus Nephritis
Lupus nephritis (LN) is one of the most serious complications of
systemic lupus erythematosus (SLE). LN is a disease comprising a
spectrum of vascular, glomerular and tubulointerstitial lesions and
develops in approximately 50% of SLE patients within 10 years of
their initial diagnosis. LN is associated with considerable
morbidity, including an increased risk of end-stage renal disease
requiring dialysis or renal transplantation and an increased risk
of death. There are limited approved therapies for the treatment of
LN. Management typically consists of induction therapy to achieve
remission and long-term maintenance therapy to prevent relapse.
About Kezar Life Sciences
Kezar Life Sciences is a clinical-stage biopharmaceutical
company discovering and developing novel treatments for
immune-mediated and oncologic disorders. The company is pioneering
first-in-class, small-molecule therapies that harness master
regulators of cellular function to inhibit multiple drivers of
disease via single, powerful targets. Zetomipzomib, its lead
development asset, is a selective immunoproteasome inhibitor has
completed a Phase 2 clinical trial in lupus nephritis. This product
candidate also has the potential to address multiple chronic
immune-mediated diseases. KZR-261 is the first anti-cancer clinical
candidate from the company’s platform targeting the Sec61
translocon and the protein secretion pathway. An open-label
dose-escalation Phase 1 clinical trial of KZR-261 to assess safety,
tolerability and preliminary tumor activity in solid tumors is
underway. For more information, visit
www.kezarlifesciences.com.
Cautionary Note on Forward-looking Statements
This press release contains forward-looking statements within
the meaning of the Private Securities Litigation Reform Act of
1995. Words such as “may,” “will,” “should,” “expect,” “believe”,
“potential,” “plan” and similar expressions (as well as other words
or expressions referencing future events, conditions or
circumstances) are intended to identify forward-looking statements.
These forward-looking statements are based on Kezar’s expectations
and assumptions as of the date of this press release. Each of these
forward-looking statements involves risks and uncertainties that
could cause Kezar’s clinical development programs, future results
or performance to differ materially from those expressed or implied
by the forward-looking statements. Forward-looking statements
contained in this press release include, but are not limited to,
statements about the design, progress, timing, scope and results of
clinical trials, the anticipated clinical and regulatory
development and future clinical trials involving zetomipzomib, the
likelihood that data will support future development and
therapeutic potential and the association of data with treatment
outcomes. Many factors may cause differences between current
expectations and actual results, including unexpected safety or
efficacy data observed during clinical studies, changes in expected
or existing competition, the uncertainties and timing of the
regulatory approval process and unexpected litigation or other
disputes. Other factors that may cause actual results to differ
from those expressed or implied in the forward-looking statements
in this press release are discussed in Kezar’s filings with the
U.S. Securities and Exchange Commission, including the “Risk
Factors” contained therein. Except as required by law, Kezar
assumes no obligation to update any forward-looking statements
contained herein to reflect any change in expectations, even as new
information becomes available.
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version on businesswire.com: https://www.businesswire.com/news/home/20221103005618/en/
Investor: Gitanjali Jain Vice President, Investor
Relations and External Affairs gjain@kezarbio.com
Media: Julia Deutsch Solebury Strategic Communications
jdeutsch@soleburystrat.com
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