Kiniksa Pharmaceuticals, Ltd. (Nasdaq: KNSA) (“Kiniksa”), a
biopharmaceutical company with a pipeline of clinical-stage assets
designed to modulate immunological pathways across a spectrum of
diseases, announced positive data from the global Phase 2 trial of
mavrilimumab in giant cell arteritis (GCA). Mavrilimumab is an
investigational fully-human monoclonal antibody that targets
granulocyte macrophage colony stimulating factor receptor alpha
(GM-CSFRα). The trial achieved both the primary and secondary
efficacy endpoints with statistical significance.
“We are thrilled to report that both the primary and secondary
efficacy endpoints in the Phase 2 trial of mavrilimumab in giant
cell arteritis achieved statistical significance,” said Sanj K.
Patel, Chief Executive Officer and Chairman of the Board of
Kiniksa. “These data suggest mavrilimumab may offer a treatment
option for patients suffering from giant cell arteritis and further
demonstrate the potential broad utility of mavrilimumab. We look
forward to presenting additional data from this study in a
publication or at a future medical conference.”
The randomized, double-blind, placebo-controlled, global Phase 2
trial consists of a 6-week screening period, a 26-week double-blind
placebo-controlled treatment period, and a 12-week washout safety
follow-up period. Patients age 50 to 85 years with active GCA,
confirmed by temporal artery biopsy and/or imaging, with
erythrocyte sedimentation rate (ESR) ≥ 30 mm/hour or C-reactive
protein (CRP) ≥ 1 mg/dL, and symptoms of GCA within 6 weeks from
randomization, were included. All patients were required to have
achieved corticosteroid-induced remission (resolution of symptoms,
ESR < 20 mm/hour, CRP < 1 mg/dL) prior to randomization.
Seventy (70) patients were randomized 3:2 to mavrilimumab 150 mg or
placebo biweekly injected subcutaneously, co-administered with a
protocol-defined 26-week oral corticosteroid taper. Patients were
stratified by new onset (n=35) or relapsing/refractory (n=35)
disease. The co-principal investigators are Dr. Maria
Cid, Hospital Clínic, University of Barcelona, IDIBAPS, and
Dr. Sebastian Unizony of Massachusetts General Hospital, Harvard
University.
The primary efficacy endpoint of time-to-first adjudicated GCA
flare by Week 26 in all treated patients was statistically
significant (Hazard Ratio = 0.38, p=0.0263).
- Median time-to-flare by Week 26
could not be estimated in mavrilimumab recipients due to the low
number of flares in the mavrilimumab treatment arm. The median
time-to-flare for placebo recipients was 25.1 weeks. There was a
62% lower risk of flare in mavrilimumab recipients compared to
placebo recipients.
The secondary efficacy endpoint of sustained remission at Week
26 in all treated patients was also statistically significant.
- The sustained remission rate at
Week 26 was 33.3 percentage points higher in mavrilimumab
recipients (83.2%) compared to placebo recipients (49.9%)
(p=0.0038).
Mavrilimumab was well-tolerated; there were no drug-related
serious adverse events, and the rates of drug-related
treatment-emergent adverse events between mavrilimumab recipients
and placebo recipients were similar.
The 12-week washout safety follow-up period and additional
analyses of this Phase 2 trial are ongoing. Next steps for the
development program in GCA will be further informed by anticipated
discussions with the U.S. Food and Drug Administration (FDA).
“We believe there is significant unmet need for safe and
effective giant cell arteritis therapies, given that approximately
only half of patients can achieve sustained remission on a yearly
basis on current standard of care,” said John F. Paolini, MD, PhD,
Chief Medical Officer of Kiniksa. “Novel therapies which safely
provide long-term sustained remission in this aging patient
population with comorbidities are needed. Mavrilimumab, with its
upstream inhibition of two immune pathways implicated in giant cell
arteritis, has the potential to provide differentiation by
addressing the underlying pathophysiology of the disease.”
Preclinical data, previously shown at scientific conferences and
available through the Science section of Kiniksa’s website, support
the mechanistic rationale of targeting the granulocyte macrophage
colony stimulating factor (GM-CSF) pathway upstream in patients
with GCA. GM-CSF and downstream T helper type 1 (TH1) cell and T
helper type 17 (TH17) cell pathways were demonstrated to be
activated at the ribonucleic acid and protein level in arteries
from GCA patients compared to healthy controls, and mavrilimumab
was demonstrated to inhibit production of inflammatory molecules
characteristic of GCA pathophysiology in an ex vivo culture model
of arteries from GCA patients1. Additionally, in an in vivo model
of human GCA, mavrilimumab reduced arterial inflammation and gamma
interferon production2.
The FDA recently granted Orphan Drug designation to mavrilimumab
for the treatment of GCA.
Kiniksa is also evaluating mavrilimumab in severe COVID-19
pneumonia and hyperinflammation and is enrolling the Phase 2
portion of a global, randomized, double-blind, placebo-controlled
adaptive design Phase 2/3 clinical trial. Additionally, data are
expected from a randomized, double-blind, placebo-controlled
investigator-initiated study in the U.S. in the fourth
quarter of 2020.
1 Poster presentation at European Congress of Rheumatology 2019
(EULAR): GM-CSF Pathway Signature Identified in Temporal Artery
Biopsies of Patients With Giant Cell Arteritis Maria C. Cid, Rohan
Gandhi, Marc Corbera-Bellalta, Nekane Terrades-Garcia, Sujatha
Muralidharan, John F. Paolini; 2 Presentation at 2019 American
College of Rheumatology (ACR): GM-CSF is a Pro-Inflammatory
Cytokine in Experimental Vasculitis of Medium and Large Arteries
Ryu Watanabe, Hui Zhang, Toshihisa Maeda, Mitsuhiro Akiyama, Rohan
Gandhi, John F. Paolini, Gerald J. Berry, Cornelia M. Weyand
About Giant Cell ArteritisGiant cell arteritis
is a rare chronic inflammatory disease of medium-to-large arteries.
Cranial giant cell arteritis typically presents with headache and
jaw claudication as well as constitutional symptoms of fever and
fatigue. Acute events can include permanent vision loss from
diminished blood flow to the eye. The large vessel form of giant
cell arteritis affects the branches of the aorta supplying the
trunk and limbs. There is currently one FDA-approved treatment for
giant cell arteritis as an adjunct to a corticosteroid taper.
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 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 clinical-stage 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: mavrilimumab’s potential to offer
a treatment option for patients with giant cell arteritis; the
potential broad utility of mavrilimumab; the unmet need for
patients with GCA; mavrilimumab’s potential to address the
underlying pathophysiology of the disease; the presentation of
additional data from the study in a publication or future medical
conference; anticipated discussions with the FDA on our development
program in GCA and its potential to impact next steps for the
program; the timing of data from our clinical trials; and the
potential for 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,
investigator-initiated studies or other companies; the potential
for undesirable side effects to be caused by mavrilimumab; the
potential inability to replicate in later clinical trials positive
results from earlier studies or clinical trials; the impact of
discussions with the FDA on our development program in GCA; our
reliance on third parties to manufacture our product candidates and
conduct our clinical trials and/or perform certain regulatory
activities for our product candidates; drug substance and/or drug
product shortages; our engagement of a manufacturing organization
to produce mavrilimumab beyond our current inventory; 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 August 4, 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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