- Tarcocimab tedromer (KSI-301) dosed every two months met the
primary endpoint of non-inferior visual acuity gains compared to
aflibercept dosed every month
- First anti-VEGF therapy to achieve non-inferiority in visual
acuity gains while doubling the treatment interval in patients with
RVO
- Tarcocimab was well tolerated with a low rate of intraocular
inflammation and no new or unexpected safety signals
- Study results will be presented at upcoming ophthalmology
scientific meetings in September
2022
PALO
ALTO, Calif., Aug. 8, 2022
/PRNewswire/ -- Kodiak Sciences Inc. (Nasdaq: KOD) today announced
that its BEACON Phase 3 study of tarcocimab tedromer (KSI-301;
tarcocimab), its novel antibody biopolymer conjugate, met the
primary endpoint of non-inferior change from baseline in visual
acuity at week 24 compared to aflibercept in patients with macular
edema due to retinal vein occlusion. Tarcocimab also demonstrated
robust anatomic responses and a favorable safety profile. After two
initial monthly loading doses, tarcocimab was dosed every two
months compared to consistent monthly dosing for aflibercept.
"RVO is a disease with a heavy treatment burden, and all
approved anti-VEGF treatments for RVO are labeled for monthly
dosing," said Mark Barakat, MD,
Director of the Retinal Research Institute at Retinal Consultants
of Arizona and a BEACON study
investigator. "BEACON is the first study to successfully test a
doubling of the treatment interval for anti-VEGF dosing in a
pivotal trial in RVO patients. Testing only two loading doses and
an extended, fixed dosing interval for all patients rather than
assigning a subset of patients to extended dosing based on disease
activity assessment is an especially high bar because eyes of
patients with RVO can have the highest VEGF levels across retinal
vascular diseases. It's wonderful news for patients that the study
was successful: it showed that treatment with tarcocimab results in
non-inferior vision outcomes, while meaningfully reducing the
treatment burden compared to monthly aflibercept."
The BEACON study is a randomized, double-masked, multicenter,
active comparator-controlled Phase 3 clinical trial in treatment
naïve patients with vision loss and macular edema due to retinal
vein occlusion, including both branch (BRVO) and central (CRVO)
subtypes. This condition occurs when a branch or central draining
vein of the retina becomes blocked, for example due to chronic
hypertension, and the retina becomes swollen as a result. The study
randomized 568 participants (438 BRVO, 130 CRVO) from 11 countries
1:1 into two treatment arms: tarcocimab tedromer 5 mg on a
fixed every-8-week dosing regimen following 2 monthly loading doses
and aflibercept 2 mg on a fixed every 4-week dosing regimen per its
label.
The primary efficacy endpoint of the study was change in
best-corrected visual acuity (BCVA) score, a measure of the best
vision a person can achieve when reading letters on an eye chart,
from baseline at week 24. In the first 24 weeks of the study,
patients randomized to tarcocimab received a total of 4 doses
compared with 6 doses received by patients randomized to
aflibercept.
The non-inferiority margin for the comparison to aflibercept at
week 24 was established at 4.5 eye chart letters based on pretrial
regulatory feedback and precedent. Under the study's prespecified
statistical analysis plan and hierarchical testing strategy for
control of type 1 error, non-inferiority of tarcocimab to
aflibercept was first demonstrated in patients with branch RVO,
with a statistically significant p-value of 0.0004, and then also
demonstrated with a statistically significant p-value of 0.0243 in
the overall RVO population (branch and central types combined).
Tarcocimab tedromer was safe and well tolerated in the study, with
no new safety signals identified. A low rate of intraocular
inflammation was observed in both groups (1.4% vs 0.4% for
tarcocimab and aflibercept, respectively) with no vasculitis or
retinal arterial occlusion events reported in any patient.
"The positive results of the BEACON study show that tarcocimab
can rapidly, robustly and safely improve vision and retinal anatomy
in patients with macular edema due to RVO while substantially
reducing the number of eye injections," said Jason Ehrlich, MD, PhD, Chief Medical Officer
and Chief Development Officer of Kodiak. "We're hopeful that BEACON
also bodes well for our ongoing Phase 3 GLEAM and GLIMMER studies
of tarcocimab in diabetic macular edema, because both RVO and DME
are diseases of the inner retina in which elevated VEGF levels in
the vitreous and retina result in retinal vascular leakage and
retinal swelling. We thank the patients who participated in BEACON
and the many clinicians, site staff and Kodiak team members who
worked together on this study and the broad tarcocimab clinical
program."
"Our regulatory strategy is designed to have two successful
studies in one indication and then individual studies in additional
indications. Looking across our development program for tarcocimab,
our paired Phase 3 GLEAM and GLIMMER studies in DME, if successful,
are designed to serve as the primary basis for a licensing
application and potential regulatory approval of tarcocimab," said
Victor Perlroth, MD, Kodiak's Chief
Executive Officer. "BEACON serves as the single pivotal study to
support approval in macular edema following RVO. Our Phase 3
DAYLIGHT study and our Phase 3 GLOW study, if successful, would
contribute data to support approvals in wet AMD and
Non-Proliferative Diabetic Retinopathy (NPDR), respectively. All
the studies are fully enrolled and expected to read out topline
data within the next twelve months and, if successful, we would
plan to file a single Biologics License Application (BLA) with the
data across the program. As we learn more from the remaining Phase
3 studies, we look forward to continuing to work with the FDA and
global health authorities to bring this medicine to patients."
Full primary results from the BEACON study are expected to be
presented by BEACON Study Investigators at upcoming ophthalmology
congresses in September 2022.
About the BEACON Study
The Phase 3 BEACON study is a global, multi-center, randomized
study designed to evaluate the durability, efficacy and safety of
tarcocimab tedromer in patients with treatment-naïve macular edema
due to retinal vein occlusion, including both branch and central
subtypes. Patients are randomized 1:1 to receive tarcocimab 5 mg or
aflibercept 2 mg. In the first six months, patients receiving
tarcocimab are treated with a proactive, fixed regimen which
includes two monthly loading doses followed by treatment every 8
weeks, and patients receiving aflibercept are treated monthly as
per its label. In the second six months, patients in both groups
will receive treatment on an individualized basis per
protocol-specified criteria. Following this, patients can continue
to receive tarcocimab tedromer for an additional six months on an
individualized basis. The study completed enrollment of 568
patients worldwide in the fourth quarter of 2021 and met its
primary efficacy endpoint at six months. Results from the BEACON
study are intended to serve as the basis for the potential approval
of tarcocimab in RVO. Additional information about the BEACON study
(also called Study KS301P103) can be found on
www.clinicaltrials.gov under Trial Identifier NCT04592419
(https://clinicaltrials.gov/show/NCT04592419).
About Retinal Vein Occlusion
Retinal Vein Occlusion (RVO) is a condition that results from
blockage of the veins that carry blood away from the retina, the
light sensitive tissue at the back of the eye. It is the second
most common cause of vision loss due to retinal vascular disease.
RVO is more likely to occur in patients who are older or have
health conditions such as high blood pressure, diabetes, high
cholesterol levels or a history of smoking or other health problems
which affect vascular health or blood flow. Branch RVO (BRVO)
occurs when a branch of the eye's retinal venous drainage system
becomes blocked, and central RVO (CRVO) occurs when the eye's
central retinal vein becomes blocked. RVO typically results in
sudden, painless vision loss in the affected eye, because the
venous blockage restricts normal blood flow in the affected retina,
resulting in ischemia, bleeding, fluid leakage, and retinal
swelling (called macular edema). Macular edema due to RVO is
typically treated with repeated intravitreal injection of
anti-vascular endothelial growth factor (VEGF) therapies. It is
estimated that 16.4 million adults worldwide are affected by RVO –
13.9 million with BRVO and 2.5 million with CRVO. In the United States, approximately 850,000
adults have BRVO, and approximately 300,000 have CRVO.
About tarcocimab tedromer (KSI-301)
Tarcocimab tedromer is an investigational anti-VEGF therapy
built on Kodiak's Antibody Biopolymer Conjugate (ABC) Platform and
is designed to maintain potent and effective drug levels in ocular
tissues for longer than existing available agents. Kodiak's
objective with tarcocimab tedromer is to improve outcomes for
patients with retinal vascular diseases and to enable earlier
treatment and prevention of vision loss for patients with diabetic
eye disease. Kodiak is developing tarcocimab to be a new first-line
agent which enables a majority of patients to be treated and
maintained on an every 5 to 6-month treatment interval and a
minority of high need patients to be treated as frequently as
monthly. The tarcocimab tedromer clinical program is designed to
assess the product's durability, efficacy and safety in wet AMD,
DME, RVO and non-proliferative DR (without DME) through clinical
studies run in parallel. The Company's GLEAM and GLIMMER pivotal
studies in patients with diabetic macular edema, the BEACON pivotal
study in patients with retinal vein occlusion, the DAYLIGHT pivotal
study in patients with wet AMD, and the GLOW study in patients with
NPDR are anticipated to form the basis of the Company's BLA to
support potential approval and commercialization in multiple
indications. The global tarcocimab tedromer clinical program is
being conducted at 150+ study sites in more than 10 countries.
Kodiak is developing and owns global rights to tarcocimab
tedromer.
About Kodiak Sciences Inc.
Kodiak (Nasdaq: KOD) is a biopharmaceutical company committed to
researching, developing and commercializing transformative
therapeutics to treat high prevalence retinal diseases. Founded in
2009, we are focused on bringing new science to the design and
manufacture of next generation retinal medicines to prevent and
treat the leading causes of blindness globally. Our ABC Platform™
uses molecular engineering to merge the fields of antibody-based
and chemistry-based therapies and is at the core of Kodiak's
discovery engine. Kodiak's lead product candidate, tarcocimab
tedromer, is a novel anti-VEGF antibody biopolymer conjugate being
developed for the treatment of retinal vascular diseases including
wet age-related macular degeneration, the leading cause of
blindness in elderly patients in the developed world, and diabetic
eye diseases, the leading cause of blindness in working-age
patients in the developed world. Kodiak has leveraged its ABC
Platform to build a pipeline of product candidates in various
stages of development. KSI-501 is our dual inhibitor antibody
biopolymer conjugate targeting both VEGF (VEGF-trap) and IL-6
(anti-IL-6 antibody) for the treatment of retinal diseases. We are
expanding our early research pipeline to include ABC Platform based
triplet inhibitors for multifactorial retinal diseases such as dry
AMD and glaucoma. Kodiak is based in Palo
Alto, CA. For more information, please visit
www.kodiak.com.
About the GLEAM and GLIMMER Studies
The Phase 3 GLEAM and GLIMMER studies are global, multi-center,
randomized pivotal studies designed to evaluate the durability,
efficacy and safety of tarcocimab in patients with treatment-naïve
diabetic macular edema. In each study, patients are randomized 1:1
to receive either tarcocimab or aflibercept. The tarcocimab arm is
treated with a proactive, individualized dosing regimen of every
8-, 12-, 16-, 20- or 24 weeks (utilizing tight dynamic retreatment
criteria) after three loading doses. The aflibercept arm is treated
with a fixed dosing regimen of every 8-weeks after five monthly
loading doses, per its label. Both studies completed enrollment of
approximately 450 patients each worldwide in the first quarter of
2022. The primary endpoint for both studies is the average of weeks
60 and 64, and patients will be treated and followed for a total of
two years. We expect to announce topline data in mid-2023. If
successful, we expect that data from our GLEAM and GLIMMER studies
will serve as the primary basis for approval of tarcocimab in our
anticipated BLA submission. Additional information about GLEAM
(also called Study KS301P104) and GLIMMER (also called Study
KS301P105) can be found on www.clinicaltrials.gov under Trial
Identifiers NCT04611152 and NCT04603937, respectively
(https://clinicaltrials.gov/ct2/show/NCT04611152 and
https://clinicaltrials.gov/ct2/show/NCT04603937).
About the DAYLIGHT Study
The Phase 3 DAYLIGHT study is a global, multi-center, randomized
pivotal study designed to evaluate the efficacy and safety of
high-frequency tarcocimab in patients with treatment-naïve wet AMD.
Patients are randomized to receive either tarcocimab on a monthly
dosing regimen or to receive standard-of-care aflibercept on a
fixed dosing regimen of every 8-weeks after three monthly loading
doses per its label. The primary endpoint is the average of weeks
40, 44 and 48. The DAYLIGHT study is intended to clarify the
efficacy of tarcocimab to treat high need patients with wet AMD
and, if successful, is intended to serve as the basis for approval
in wet AMD with monthly dosing. DAYLIGHT has completed enrollment
of approximately 550 patients worldwide and we expect to announce
topline data in mid-2023. Additional information about DAYLIGHT
(also called Study KS301P107) can be found on
www.clinicaltrials.gov under Trial Identifier NCT04964089
(https://clinicaltrials.gov/show/NCT04964089).
About the GLOW Study
The Phase 3 GLOW study is a global, multi-center, randomized
pivotal superiority study designed to evaluate the efficacy and
safety of tarcocimab tedromer in approximately 240 patients with
treatment-naïve, moderately severe to severe non-proliferative
diabetic retinopathy (NPDR). Patients are randomized to receive
either tarcocimab every six months after initiating doses given at
baseline, 8 weeks and 20 weeks into the study, or to receive sham
injections. The primary endpoint is at one year and patients will
be treated and followed for two years. Outcomes include changes in
diabetic retinopathy severity, measured on a standardized
photographic grading scale, and the rate of development of
sight-threatening complications due to diabetic retinopathy. We
believe tarcocimab tedromer has the potential to be the
longest-interval intravitreal therapeutic option for patients with
diabetic retinopathy. GLOW has completed enrollment of
approximately 240 patients in August
2022. Additional information about GLOW (also called Study
KS301P106) can be found on www.clinicaltrials.gov under Trial
Identifier NCT05066230
(https://clinicaltrials.gov/show/NCT05066230).
Forward-Looking Statements
This release contains "forward-looking statements" within the
meaning of Section 27A of the Securities Act of 1933, Section 21E
of the Securities Exchange Act of 1934 and the Private Securities
Litigation Reform Act of 1995. These forward-looking statements are
not based on historical fact and include statements regarding the
potential of tarcocimab to treat and prevent vision loss in certain
patients, including the potential to improve vision and anatomic
responses while substantially reducing the number of eye injections
and the treatment burden for RVO patients; the potential
implications of BEACON results for additional studies; our
regulatory strategy, including the expected timing of results from
various studies and the bases on which regulatory approval may be
sought;. Forward-looking statements generally include statements
that are predictive in nature and depend upon or refer to future
events or conditions, and include words such as "may," "will,"
"should," "would," "could," "expect," "plan," "believe," "intend,"
"pursue," and other similar expressions among others. Any
forward-looking statements are based on management's current
expectations of future events and are subject to a number of risks
and uncertainties that could cause actual results to differ
materially and adversely from those set forth in or implied by such
forward-looking statements. These risks and uncertainties include,
but are not limited to, the risk that preliminary safety, efficacy
and durability data for our tarcocimab tedromer product candidate
may not continue or persist; the risk that tarcocimab tedromer may
not have the anti-VEGF effect or impact on the treatment of RVO
expected; cessation or delay of any of the ongoing clinical studies
and/or our development of tarcocimab tedromer may occur, including
as a result of the ongoing COVID-19 pandemic; the risk that our ABC
Platform may not extend treatment intervals in retinal disorders as
anticipated, or at all; future potential regulatory milestones of
tarcocimab tedromer, including those related to current and planned
clinical studies, may be insufficient to support regulatory
submissions or approval; adverse economic conditions may
significantly impact our business and operations, including our
clinical trial sites, and those of our manufacturers, contract
research organizations or other parties with whom we conduct
business; as well as the other risks identified in our filings with
the Securities and Exchange Commission. For a discussion of other
risks and uncertainties, and other important factors, any of which
could cause our actual results to differ from those contained in
the forward-looking statements, see the section entitled "Risk
Factors" in our most recent Form 10-K, as well as discussions of
potential risks, uncertainties, and other important factors in our
subsequent filings with the Securities and Exchange Commission.
These forward-looking statements speak only as of the date hereof
and Kodiak undertakes no obligation to update forward-looking
statements, and readers are cautioned not to place undue reliance
on such forward-looking statements. Kodiak®, Kodiak Sciences®,
ABC™, ABC Platform™ and the Kodiak logo are registered trademarks
or trademarks of Kodiak Sciences Inc. in various global
jurisdictions.
References:
1. Klein R, Klein BE, Moss SE, Meuer SM. The epidemiology of
retinal vein occlusion: the Beaver Dam Eye Study. Trans Am
Ophthalmol Soc. 2000;98:133–141.
2. Klein R, Moss SE, Meuer SM, et al. The 15-year cumulative
incidence of retinal vein occlusion: the Beaver Dam Eye Study. Arch
Ophthalmol. 2008;126:513–518.
3. Rogers S, McIntosh RL, Cheung N, et al. The prevalence of
retinal vein occlusion: pooled data from population studies from
the United States, Europe, Asia,
and Australia. Ophthalmology.
2010;117:313–319.e1.
4. Rehak J, Rehak M. Branch retinal vein occlusion:
pathogenesis, visual prognosis, and treatment modalities. Curr Eye
Res. 2008;33:111-131.
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