Kiniksa Pharmaceuticals, Ltd. (Nasdaq: KNSA) (“Kiniksa”), a
biopharmaceutical company with a pipeline of assets designed to
modulate immunological pathways across a spectrum of diseases,
today announced data from the investigator-initiated
placebo-controlled study of mavrilimumab in patients with severe
COVID-19 pneumonia and hyperinflammation. Enrollment in the study
was closed early to focus on Kiniksa’s registrational development
program in the same patient population.
“The data showed encouraging trends of reduced mortality and
duration of mechanical ventilation in patients treated with
mavrilimumab, especially when considering that many patients in
this placebo-controlled study had already been treated with
remdesivir and/or corticosteroids,” said John F. Paolini,
MD, PhD, Chief Medical Officer of Kiniksa. “These data are
comparable to the data from the open-label treatment protocol
reported in June of 2020. We believe the totality of these two data
sets supports continued evaluation of mavrilimumab in severe
COVID-19 pneumonia and hyperinflammation.”
The investigator-initiated study was a randomized, double-blind,
placebo-controlled study across a consortium of U.S. academic
sites, including Cleveland Clinic, University of Cincinnati, and
Virginia Commonwealth University, designed to evaluate the efficacy
and safety of mavrilimumab versus placebo on top of standard of
care therapy in patients with severe COVID-19 pneumonia and
hyperinflammation. The study enrolled 40 patients with severe
COVID-19 pneumonia (all patients presented with pneumonia and
hypoxia: all patients required supplemental oxygen, 50% of patients
required non-invasive ventilation, none required mechanical
ventilation at baseline; median PaO2/FiO2 ratio 137) and
hyperinflammation (median C-reactive protein 13.1 mg/dL).
Concomitant medications at baseline included corticosteroids (65%
of patients) and remdesivir (75% of patients). Patients were
randomized 1:1 to a single intravenous (IV) infusion of
mavrilimumab 6mg/kg (n=21) or placebo (n=19) and were followed for
at least 60 days.
Data showed an early signal of efficacy, with trends toward
clinical improvement as well as lower mortality and shorter
duration of mechanical ventilation in patients treated with
mavrilimumab on top of corticosteroids, including dexamethasone,
and/or remdesivir.
- There was a 20.5% relative increase
in the primary efficacy endpoint, the proportion of patients alive
and off supplemental oxygen at Day 14 (mavrilimumab: 57.1% [n=21];
placebo: 47.4% [n=19]; nominal p=0.536).
- There was a 20.7% relative increase
in the secondary efficacy endpoint, the proportion of patients
alive and without respiratory failure at Day 28 (mavrilimumab:
95.2%; placebo: 78.9%; nominal p=0.172).
- There was 1 death (4.8%) in the
mavrilimumab arm by Day 28, compared to 3 deaths (15.8%) in the
placebo arm (nominal p=0.222). By Day 60 there was 1 death (4.8%)
in the mavrilimumab arm, compared to 4 deaths (21.1%) in the
placebo arm (nominal p=0.108).
- While the percentage of patients who progressed to mechanical
ventilation was similar between treatment arms (mavrilimumab: 23.8%
[n=5]; placebo: 21.1% [n=4]), the median (interquartile) duration
of mechanical ventilation was shorter in the mavrilimumab arm (12
[9.0, 18.0] days) compared to the placebo arm (17 [11.0, 24.5]
days). Additionally, 4 of the 5 patients who progressed to
mechanical ventilation in the mavrilimumab arm had recovered by Day
28, whereas all patients in the placebo arm who progressed to
mechanical ventilation had died by Day 28.
- There was no difference in serious
adverse events between the mavrilimumab arm and the placebo
arm.
“In the context of the evolving standard of care, the data from
this trial in severe COVID-19 pneumonia and hyperinflammation are
encouraging,” said Sanj K. Patel, Chief Executive Officer and
Chairman of the Board of Kiniksa. “While vaccination is expected to
be the mainstay of COVID-19 prevention, we believe there will
remain an unmet need for effective therapeutics to treat patients
who develop severe hyperinflammation. I look forward to the results
of the larger Kiniksa-sponsored trial of mavrilimumab in this
patient population.”
Kiniksa is enrolling the Phase 2 portion of an adaptive design,
placebo-controlled Phase 2/3 clinical trial in severe COVID-19
pneumonia and hyperinflammation. The company expects data from the
Phase 2 portion of the trial in the first half of 2021.
About the Investigator-Initiated Placebo-Controlled
Study of Mavrilimumab in Severe COVID-19 Pneumonia and
Hyperinflammation in the U.S.The investigator-initiated
Phase 2 trial was a randomized, double-blind, placebo-controlled
study in the U.S. designed to evaluate the efficacy and safety of
mavrilimumab versus placebo on top of standard of care therapy in
the treatment of severe COVID-19 pneumonia and hyperinflammation.
Standard of care therapy included, but was not limited to,
anti-viral treatment and/or supportive care. The trial enrolled 40
patients across a consortium of academic sites, including Cleveland
Clinic, University of Cincinnati, and Virginia Commonwealth
University. Patients were randomized 1:1 to mavrilimumab to a
single IV infusion of mavrilimumab 6 mg/kg or placebo. The primary
endpoint was the proportion of patients alive and off of
supplemental oxygen at Day 14. For more information, refer to
ClinicalTrials.gov Identifier: NCT04399980.
About Kiniksa’s Phase 2/3 Clinical Trial Protocol of
Mavrilimumab in Severe COVID-19 Pneumonia and
HyperinflammationKiniksa’s Phase 2/3 clinical trial
protocol is a global, randomized, double-blind, placebo-controlled
study encompassing 2 phases of development (Phase 2 and Phase 3).
The Phase 2 portion of the trial is expected to enroll
approximately 160 patients and is intended to evaluate the efficacy
and safety of 2 dose levels of mavrilimumab relative to placebo in
patients who have tested positive for COVID-19 and have x-ray/CT
evidence of bilateral pneumonia, active or recent fever, and
clinical laboratory results indicative of hyperinflammation. The
Phase 3 portion is expected to enroll approximately 420 patients
and is intended to confirm Phase 2 efficacy and safety findings. In
both Phase 2 and Phase 3, patients are expected to be enrolled into
2 cohorts: Cohort 1 will include non-intubated, hospitalized
patients who require supplemental oxygen to maintain SpO2 ≥ 92%,
(i.e., non-mechanically ventilated patients); and Cohort 2 will
include hospitalized patients for whom mechanical ventilation was
recently initiated within 48 hours prior to randomization (i.e.,
ventilated patients). Following screening, enrolled patients in
each cohort will be randomized 1:1:1 to receive a single IV
infusion of mavrilimumab 6mg/kg or 10 mg/kg or placebo (Day 1). The
primary efficacy endpoint for the Phase 2 portion of the trial for
Cohort 1 is the proportion of patients alive and without
respiratory failure (defined as the need for high flow oxygen,
non-invasive ventilation, invasive mechanical ventilation, or
extracorporeal membrane oxygenation) at Day 29 and for Cohort 2 is
the mortality rate by Day 29. There will be a seamless transition
in enrollment of patients in both cohorts between the Phase 2 and
Phase 3 portions of the trial. For each cohort, once the last
patient in Phase 2 is enrolled, all subsequent patients will be
considered Phase 3 patients. Once the last patient in Phase 2
completes Day 29, primary efficacy and safety analyses of the Phase
2 data will be conducted. Following demonstration of efficacy and
safety in Phase 2, the Phase 3 portion of the trial will be
continued/completed. For more information, refer to
ClinicalTrials.gov Identifier: NCT04447469.
About MavrilimumabMavrilimumab is an
investigational fully-human monoclonal antibody that targets
GM-CSFRα. Mavrilimumab was dosed in over 550 patients with
rheumatoid arthritis through Phase 2b clinical studies
in Europe and achieved prospectively-defined primary
endpoints of efficacy and safety. Kiniksa’s lead indication for
mavrilimumab is GCA, a rare inflammatory disease of medium-to-large
arteries. Kiniksa is also evaluating mavrilimumab in COVID-19
pneumonia and hyperinflammation. The FDA granted Orphan Drug
designation to mavrilimumab for the treatment of GCA in 2020.
About KiniksaKiniksa is a biopharmaceutical
company focused on discovering, acquiring, developing and
commercializing therapeutic medicines for patients suffering from
debilitating diseases with significant unmet medical need.
Kiniksa’s product candidates, rilonacept, mavrilimumab, vixarelimab
and KPL-404, are based on strong biologic rationale or validated
mechanisms, target underserved conditions and offer the potential
for differentiation. These pipeline assets are designed to modulate
immunological pathways across a spectrum of diseases. For more
information, please visit www.kiniksa.com.
Forward-Looking StatementsThe information
contained in this press release contains forward-looking statements
within the meaning of the Private Securities Litigation Reform Act
of 1995. In some cases, you can identify forward looking statements
by terms such as “may,” “will,” “should,” “expect,” “plan,”
“anticipate,” “could,” “intend,” “target,” “project,”
“contemplate,” “believe,” “estimate,” “predict,” “potential” or
“continue” or the negative of these terms or other similar
expressions, although not all forward-looking statements contain
these identifying words. All statements contained in this press
release that do not relate to matters of historical fact should be
considered forward-looking statements, including without
limitation, statements regarding: our beliefs about the data from
investigator initiated study showing encouraging trends of reduced
mortality and duration of mechanical ventilation in patients
treated with mavrilimumab as well as an early signal of efficacy;
assessment as to the data from the investigator initiated study
being comparable to the data from the open-label treatment protocol
reported in June; our belief that the totality of the data
supporting continued evaluation of mavrilimumab in severe COVID-19
pneumonia and hyperinflammation; the timing of data from the Phase2
portion of our adaptive design, placebo-controlled Phase 2/3
clinical trial of mavrilimumab in severe COVID-19 pneumonia and
hyperinflammation; our belief that there will remain an unmet need
for effective therapeutics to treat patients who develop severe
hyperinflammation even with vaccination expected to be the mainstay
of COVID-19 prevention; our Phase 2/3 clinical trial designs,
including the seamless transition in enrollment of patients in both
cohorts between the Phase 2 and Phase 3 portions of the trial; and
the potential for all of our clinical stage product candidates to
offer differentiation.
These forward-looking statements are based on management’s
current expectations. These statements are neither promises nor
guarantees, but involve known and unknown risks, uncertainties and
other important factors that may cause our actual results,
performance or achievements to be materially different from any
future results, performance or achievements expressed or implied by
the forward-looking statements, including without limitation, the
following: the impact of additional data from us, or other
companies; the potential inability to replicate in later clinical
trials encouraging or positive results from earlier investigator
initiated treatment protocols and studies for mavrilimumab in
severe COVID-19 pneumonia and hyperinflammation in later clinical
trials; the evolving standard of care for the treatment of patients
who develop severe COVID-19 pneumonia and hyperinflammation; the
potential for undesirable side effects to be caused by
mavrilimumab; changes to our clinical trial protocol; case rates of
severe COVID-19 pneumonia and hyperinflammation in various
geographies; our reliance on third parties to manufacture our
product candidates and conduct our clinical trials; meetings with
the Food and Drug Administration; the potential impact of the
COVID-19 pandemic and measures taken in response to the pandemic;
changes in our operating plan and funding requirements; existing or
new competition; and our ability to attract and retain qualified
personnel.
These and other important factors discussed under the caption
“Risk Factors” in our Quarterly Report on Form 10-Q filed with the
Securities and Exchange Commission (“SEC”) on November 5, 2020 and
our other reports subsequently filed with or furnished to the SEC
could cause actual results to differ materially from those
indicated by the forward-looking statements made in this press
release. Any such forward-looking statements represent management’s
estimates as of the date of this press release. While we may elect
to update such forward-looking statements at some point in the
future, we disclaim any obligation to do so, even if subsequent
events cause our views to change. These forward-looking statements
should not be relied upon as representing our views as of any date
subsequent to the date of this press release.
Every Second
Counts!™Kiniksa Investor and Media
ContactMark Ragosa(781) 430-8289mragosa@kiniksa.com |
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