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 that new data from the global Phase 2 clinical
trial of mavrilimumab in giant cell arteritis (GCA) will be
presented at the late-breaking abstracts session during the
American College of Rheumatology (ACR) Convergence 2020.
Mavrilimumab is an investigational fully-human monoclonal antibody
that targets granulocyte macrophage colony stimulating factor
receptor alpha (GM-CSFRα). Both the primary and secondary efficacy
endpoints achieved statistical significance, and there was a
consistent trend of efficacy across the new onset and
relapsing/refractory cohorts.
“There is a significant unmet need for safe and effective giant
cell arteritis therapies. We believe mavrilimumab, with its
upstream inhibition of two immune pathways implicated in giant cell
arteritis, has the potential to provide differentiation from
current standard of care therapies by addressing the underlying
pathophysiology of the disease,” said John F. Paolini, MD,
PhD, Chief Medical Officer of Kiniksa. “In the Phase 2 giant cell
arteritis trial, mavrilimumab was superior to placebo on the
primary and secondary efficacy endpoints of time-to-flare and
sustained remission at Week 26. These data further underscore the
potential for mavrilimumab to offer a differentiated treatment
option for patients with both relapsing/refractory disease as well
as new onset disease.”
Dr. Maria Cid1, a co-principal investigator for the global Phase
2 trial, will deliver a virtual presentation entitled Mavrilimumab
(anti GM-CSF receptor α monoclonal antibody) Reduces Time to Flare
and Increases Sustained Remission in a Phase 2 Trial of Patients
with Giant Cell Arteritis at the late-breaking abstracts session
(L06 - L11) on Monday, November 9, 2020 at 11:30 a.m. Eastern Time.
Dr. Sebastian Unizony2 is a co-principal investigator.
The Phase 2 trial randomized 70 patients 3:2 to mavrilimumab 150
mg (N=42) or placebo (N=28) 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 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).
While the study was not powered for disease cohorts, there was a
consistent trend of efficacy across the new onset and
relapsing/refractory cohorts.
New Onset Cohort
- There was a 71% lower risk of flare
in mavrilimumab recipients compared to placebo recipients (Hazard
Ratio = 0.29, p=0.0873).
- The sustained remission rate at
Week 26 was 28.9 percentage points higher in mavrilimumab
recipients (91.3%) compared to placebo recipients (62.3%)
(p=0.0727).
Relapsing/Refractory Cohort
- There was a 57% lower risk of flare
in mavrilimumab recipients compared to placebo recipients (Hazard
Ratio = 0.43, p=0.1231).
- The sustained remission rate at
Week 26 was 30.6 percentage points higher in mavrilimumab
recipients (72.2%) compared to placebo recipients (41.7%)
(p=0.0668).
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 is ongoing, and
additional analyses of this Phase 2 trial are planned. Next steps
for the development program in GCA will be further informed by
anticipated discussions with the U.S. Food and Drug Administration
(FDA).
The abstract is available through the ACR website.
Table 1 as submitted to ACR by the authors for publication and
as referenced in the abstract follows below. The table was
inadvertently omitted during the online posting of the
abstract.
Table 1: Efficacy at Week 26.
Time to Flare by Week 26 and Sustained Remission at Week 26
- Total mITT Population |
|
Mavrilimumab 150 mg (N=42) |
Placebo(N=28) |
Number of
Subjects with Flare, n (%) |
8 (19.0) |
13 (46.4) |
|
Primary Efficacy Endpoint: Time to Flare (weeks) by Week 26
[1] |
|
|
Median, 95% CI |
NE (NE, NE) |
25.1 (16.0, NE) |
Hazard Ratio (Mavrilimumab vs Placebo), 95% CI [2] |
0.38 (0.15, 0.92) |
|
P-value [3] |
0.0263 |
|
|
Secondary Efficacy Endpoint: Sustained
Remission at Week 26 (%), 95% CI
[4] |
83.2 (67.9, 91.6) |
49.9 (29.6, 67.3) |
Difference in Proportions (95% CI) [5] |
33.3 (10.7, 55.8) |
|
P-value [5] |
0.0038 |
|
|
|
|
Time to Flare by Week 26 and Sustained Remission at Week 26
by Randomization Strata |
|
New-onset |
Relapsing/Refractory |
|
Mavrilimumab 150 mg(N=24) |
Placebo(N=11) |
Mavrilimumab 150 mg(N=18) |
Placebo(N=17) |
Number of
Subjects with Flare, n (%) |
3 (12.5) |
4 (36.4) |
5 (27.8) |
9 (52.9) |
|
Primary Endpoint: Time to Flare (weeks) by Week 26
[1] |
|
|
|
|
Median, 95% CI |
NE (NE, NE) |
NE (11.7, NE) |
NE (16.4, NE) |
22.6 (16.0, NE) |
Hazard Ratio (Mavrilimumab vs Placebo), 95% CI [6] |
0.29 (0.06, 1.31) |
|
0.43 (0.14, 1.30) |
|
P-value [7] [8] |
0.0873 |
|
0.1231 |
|
|
Secondary Endpoint: Sustained Remission at Week 26 (%) ,
95% CI [4] |
91.3 (69.3, 97.7) |
62.3 (27.7, 84.0) |
72.2 (45.6, 87.4) |
41.7 (17.4, 64.5) |
Difference in Proportions (95% CI) [5] |
28.9 (-2.7, 60.5) |
|
30.6 (-2.1, 63.2) |
|
P-value [5][8] |
0.0727 |
|
0.0668 |
|
NE = Not estimable.
[1] Kaplan-Meier method used to estimate the survival functions for
each treatment arm. [2] Calculated based on a Cox
proportional-hazards model with treatment as covariate and
stratified by randomization strata. [3] Comparison of KPL-301 and
placebo with respect to time to flare calculated by using a
log-rank test and stratified by randomization strata.[4]
Kaplan-Meier Survival Estimates with standard error and 95% CI for
each arm. [5] Two-sided p-value and 95% CI for the difference in
sustained remission between two arms using normal approximation.
Placebo arm is the reference. [6] Calculated based on a
Cox proportional-hazards model with treatment as covariate. [7]
Comparison of KPL-301 and placebo with respect to time to flare
calculated by using a log-rank test.[8] Subgroup analyses were not
powered for significance; nominal p values reported. |
|
|
The FDA recently granted Orphan Drug designation to mavrilimumab
for the treatment of GCA.
Kiniksa intends to make the presentation available through the
Science section of its website after the ACR embargo lifts.
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, the company
expects to announce data from a randomized, double-blind,
placebo-controlled investigator-initiated study in
the U.S. in the fourth quarter of 2020.
1 Hospital Clínic, University of Barcelona, Institut
d’Investigacions Biomèdiques August Pi i Sunyer
(IDIBAPS); 2 Massachusetts General Hospital, Harvard University
About the Global Phase 2 Clinical Trial of Mavrilimumab
in GCAThe randomized, double-blind, placebo-controlled,
global Phase 2 clinical trial of mavrilimumab in GCA 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.
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 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 both patients with relapsing/refractory
disease as well as those with new onset disease in giant cell
arteritis (“GCA”); the unmet need for patients with GCA; the
potential to provide differentiation from current standard of care
therapies by mavrilimumab’s potential to address the underlying
pathophysiology of the disease; the presentation of data from the
study in an upcoming medical conference; 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, including in connection with 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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