- Most patients saw clinically meaningful improvements in the
primary endpoint measure of Total Improvement Score (TIS), but no
differentiation from placebo was observed
- Zetomipzomib demonstrates a favorable safety and tolerability
profile, including in the PRESIDIO Open-label Extension Study where
weekly zetomipzomib has been administered for up to an additional
77 weeks
- Topline data from MISSION Phase 2 trial of zetomipzomib in
lupus nephritis (LN) is on track and expected in June 2022,
consistent with previous guidance
Kezar Life Sciences, Inc., (Nasdaq: KZR), a clinical-stage
biotechnology company discovering and developing breakthrough
treatments for immune-mediated and oncologic disorders, today
announced topline results from the PRESIDIO Phase 2 clinical trial
of zetomipzomib (KZR-616) in patients with dermatomyositis (DM) and
polymyositis (PM).
In PRESIDIO, 25 patients enrolled with either DM (n=13) or PM
(n=12) with active disease despite best available treatments, and
20 patients completed through end-of-treatment. During the 32-week
study period, all patients received 16 weeks of zetomipzomib
treatment: patients received either 45 mg of zetomipzomib or
placebo subcutaneously (SC) once weekly for 16 weeks on top of
standard of care, followed by a crossover to the other arm of
placebo or zetomipzomib, respectively, for an additional 16 weeks.
Patients continued their background therapy but could taper
medications as clinically indicated. The primary endpoint of
PRESIDIO was the mean change in the Total Improvement Score
(TIS).
Topline results of the PRESIDIO trial showed that most DM and PM
patients saw clinically meaningful improvements in TIS, but
zetomipzomib demonstrated no significant differentiation from
placebo. At Week 16, the zetomipzomib 45 mg SC weekly group
achieved a mean TIS of 25.5 versus the control group mean TIS of
25. Following cross-over, at Week 32, the arm receiving
zetomipzomib beginning at Week 16 achieved a mean TIS of 32.5
versus the control group mean TIS of 31.3.
Safety
Zetomipzomib was well tolerated over the course of the PRESIDIO
trial. Adverse events were generally mild-to-moderate (Grade 1 or
2), and the most common treatment-emergent adverse events (TEAEs)
were injection site reactions, which were transient and manageable.
One subject withdrew from the study following an injection site
reaction at Week 9. There were three Grade 3 serious adverse events
in the zetomipzomib arms, all deemed unrelated to zetomipzomib,
which occurred in two patients and did not result in
discontinuation from the study or change in dose. One patient
experienced a mechanical fall and syncope, and another patient had
a retinal detachment. There was one Grade 3 adverse event in a
placebo arm identified as a worsening rash. No opportunistic
infections or cytopenias were observed. Safety data is summarized
in the table below.
Safety and Tolerability of Zetomipzomib
for the 32-week PRESIDIO Trial
Patients Experiencing Adverse
Events: N (%)
Zetomipzomib
N=25
Placebo
N=22*
Any adverse event
22 (88.0)
16 (72.7)
At least 1 TEAE
22 (88.0)
16 (72.7)
Nausea
3 (12.0)
3 (13.6)
Vomiting
1 (4.0)
1 (4.5)
Most Common TEAEs
Injection-site Reaction
18 (72.0)
8 (36.4)
TEAEs = Grade 3 (all unrelated)
2 (8.0)
1 (4.5)
Infectious TEAEs ≥ Grade 3
0
0
Infectious TEAEs, all Grades
7 (28.0)
6 (27.3)
Opportunistic Infections
0
0
Serious TEAE (all unrelated)
2 (8.0)
0
*Three patients withdrew in Period 1 prior
to receiving placebo in Period 2
Open-label Extension Study
KZR-616-003E is an open-label extension (OLE) study available to
patients who completed 32 weeks in the PRESIDIO trial. Following
completion of PRESIDIO, 18 out of 20 patients enrolled in the OLE.
For the first time, patients have the option to self-administer
zetomipzomib in the OLE. Current active participation in the OLE
ranges from 2 to 77 weeks. 6 patients have discontinued
participation in OLE for reasons unrelated to zetomipzomib. No
additional safety or tolerability issues have been observed, and
mean TIS scores have improved over scores observed at the 32-week
conclusion of PRESIDIO.
“I want to thank all the investigators, site staff, Kezar
employees and most importantly the patients for their commitment to
this study in the face of profound pandemic-related headwinds.
While we are disappointed with the results of this trial, we are
encouraged by the favorable safety data and we maintain our strong
conviction in the promise of zetomipzomib in lupus nephritis and
our commitment to development of this novel agent in autoimmune
disease,” said John Fowler, CEO. “The strong response rates we’ve
seen to date in MISSION – utilizing objective endpoints in LN
patients – informs this conviction, and we look forward to sharing
topline results from that trial in June. Furthermore, our strong
financial position provides ample runway for both our zetomipzomib
and protein secretion programs, including our Phase 1 trial of
KZR-261 in solid tumors.”
Kezar’s unaudited cash position is approximately $253 million,
including cash, cash equivalents and marketable securities as of
April 30, 2022. The company plans to report the MISSION Phase 2
topline data in lupus nephritis (LN) at a Kezar corporate event in
June 2022.
About Zetomipzomib (KZR-616)
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 clinical trials provide evidence that zetomipzomib exhibits
a favorable safety and tolerability profile for development in
severe, chronic autoimmune diseases.
In addition to PRESIDIO, Kezar is conducting the MISSION Phase 2
trial in patients with lupus nephritis. Interim data from this
trial reported in November 2021 showed that of the five patients
who completed the full course of 24 weeks of weekly treatment with
zetomipzomib 60 mg doses, two achieved partial renal responses
(PRRs) and two achieved complete renal responses (CRRs).
About Dermatomyositis and Polymyositis
Dermatomyositis and Polymyositis are two of the five types of
autoimmune myositis diseases. Both are chronic, debilitating,
inflammatory autoimmune myopathies that are distinguished by
inflammation of the muscles as well as the skin (in DM).
Approximately 30,000 to 120,000 people in the United States are
living with these severe and progressive inflammatory myopathies
that are characterized by marked morbidity and associated
mortality. While debilitating muscle weakness is the hallmark of
these myopathies, including compromised muscles of respiration,
other internal organ system dysfunctions can be equally disabling.
The aim of treatment for these diseases is to suppress
inflammation, increase muscle strength and prevent long-term damage
to muscles and extramuscular organs; however, treatment options are
limited for DM, and there are currently no approved treatments for
PM.
About Kezar Life Sciences
Kezar Life Sciences is a clinical-stage biopharmaceutical
company discovering and developing breakthrough 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 being
evaluated in Phase 2 clinical trials in lupus nephritis,
dermatomyositis and polymyositis. 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,”
“promise,” “potential,” “look forward,” “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 sufficiency of Kezar’s capital and other
resources, the anticipated clinical and regulatory development of
Kezar’s product candidates, the anticipated approval of the
nonproprietary name of KZR-616, the preliminary nature of interim
and topline data, the likelihood that data will support future
development and therapeutic potential, the association of data with
treatment outcomes and the likelihood of obtaining regulatory
approval of Kezar’s product candidates. Many factors may cause
differences between current expectations and actual results,
including the availability of additional data, the confirmation of
interim and topline data resulting from trial audit and
verification procedures, unexpected safety or efficacy data
observed during clinical studies, the impacts of the COVID-19
pandemic and other global events on the company’s business and
clinical trials, changes in expected or existing competition,
changes in the regulatory environment, 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.
View source
version on businesswire.com: https://www.businesswire.com/news/home/20220503006131/en/
Gitanjali Jain Vice President, Investor Relations and External
Affairs 650-269-7523 gjain@kezarbio.com
Liza Sullivan Argot Partners 212-600-1902
kezar@argotpartners.com
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