PALO ALTO, Calif., Feb. 23, 2022 /PRNewswire/ -- Kodiak
Sciences Inc. (Nasdaq: KOD) today announced top-line results from
its randomized, double-masked, active comparator-controlled Phase
2b/3 clinical trial evaluating the
efficacy, durability and safety of KSI-301, a novel antibody
biopolymer conjugate, in treatment-naïve subjects with neovascular
(wet) age-related macular degeneration.
The trial randomized 559 participants, approximately 80% of whom
were enrolled in the United
States. The study had two treatment arms: KSI-301 5mg on a
flexible long-interval regimen and aflibercept 2mg on a fixed
short-interval regimen. In the study, three monthly loading doses
were administered to all subjects at 0-, 4- and 8-weeks. Subjects
on aflibercept were then treated at fixed 2-month intervals.
Subjects on KSI-301 were assessed starting 3 months after the
completion of the loading phase (i.e. beginning at 20 weeks)
and, based on predefined disease activity criteria, were treated
every 3-, 4-, or 5-months. As a result, patients in the KSI-301
group did not receive dosing more frequently than every 3 months at
any point in the study after the loading phase. The primary
endpoint of the study was the average 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, including with
correction such as glasses) from baseline at year 1. For the
assessment of the primary efficacy endpoint, KSI-301 patients in
all three groups (dosed every 3, 4 or 5 months) were pooled
together and their BCVA was compared as a group to the aflibercept
group (dosed every 2 months).
The results show that, although KSI-301 demonstrated strong
durability and was safe and well tolerated, it did not meet the
primary efficacy endpoint of showing non-inferior visual acuity
gains for subjects dosed on extended regimens compared to
aflibercept given every eight weeks.
A pre-specified secondary analysis at year 1 assessing
durability showed 59% of patients in the KSI-301 arm achieved
five-month dosing with visual acuity gains and anatomic
improvements comparable to the overall aflibercept group.
KSI-301 was safe and well tolerated in the study, with no new
safety signals identified.
"Allowing treatment with KSI-301 no more often than every 12
weeks after the loading phase for every patient turned out to be
insufficient," said Victor Perlroth,
MD, Kodiak's Chief Executive Officer. "Nonetheless, we believe the
results demonstrate a clear anti-VEGF effect, strong durability and
a reassuring safety profile. We think that these data continue to
support the potential of our ABC Platform to significantly extend
treatment intervals in retinal disorders in a safe and convenient
manner. Looking forward, our BEACON study in retinal vein
occlusion will have the primary endpoint visit completed in all
patients this coming June with top-line data anticipated to follow
shortly thereafter. For our GLEAM and GLIMMER long-interval studies
in diabetic macular edema as well as the DAYLIGHT short-interval
study in wet AMD, we expect top-line data in early 2023. As
our understanding of KSI-301 and the different patient populations
within retinal vascular diseases evolved, our study designs have
also evolved. One significant factor that likely contributed to
this Phase 2b/3 study missing its
primary endpoint – undertreatment of a minority of patients – is
addressed in BEACON (proactive dosing every 8 weeks) and GLEAM and
GLIMMER (tighter dynamic retreatment criteria and dosing as
frequently as every 8-weeks) and is not present in DAYLIGHT in
which all patients are proactively treated on an every 4-week
regimen."
"We learned that the study design stretched it too far for the
roughly 30% of patients who could have benefited from more VEGF
inhibition than the minimal every 3 months in the study," said Dr.
Carl Regillo, MD, Chief of the
Retina Service at Wills Eye Hospital in Philadelphia and a study investigator. "These
patients' visual acuity deteriorated, and consequently the KSI-301
treated patients overall did not achieve non-inferior visual acuity
outcomes compared to the aflibercept treated patients. But the
clear and unprecedented durability of effect for the majority of
KSI-301 patients treated with an intravitreal medicine is expected
to be a significant advance for the wet AMD patient community.
KSI-301 at year 1 brought more than half the patients on an every
5-month regimen to the 20/40 vision required to drive a motor
vehicle. Kodiak's ongoing Phase 3 program is intended to further
clarify the important role KSI-301 can play in the treatment of
retinal vascular disorders. Retinal vein occlusion and diabetic
macular edema are very different diseases from wet AMD, and
Kodiak's BEACON, GLEAM and GLIMMER study designs importantly
already provide more frequent treatment for high-need patients. The
DAYLIGHT study with its proactive monthly dosing is expected to
answer the question as to the effectiveness of early and intensive
treatment in wet AMD with KSI-301."
"Building on the observations and retreatment criteria used in
our earlier Phase 1b study, the
study's dosing interval selection criteria achieved the important
goal of identifying patients who could do well with every 5-month
dosing of KSI-301," said Jason
Ehrlich, MD, PhD, Chief Medical Officer and Chief
Development Officer of Kodiak. "This group represented a majority
of patients receiving KSI-301. At the same time, it appears from
the data that the KSI-301 patients with persistent or early
recurrent disease activity may have benefited from treatment more
frequently than what the study parameters allowed. At the time we
designed this study, it was thought that extending all wet AMD
patients to every 3-month or longer dosing was important, and we
designed our study in part with this goal in mind. The ongoing
DAYLIGHT study should clearly address the question of whether
intensive dosing with KSI-301 provides sufficient VEGF inhibition
for this important minority of patients living with wet AMD."
"On the safety front, intraocular inflammation occurred in a low
single-digit percent of KSI-301 patients (3.2%), as compared to
0.0% of patients treated with aflibercept. Recent wet AMD studies
have reported intraocular inflammation rates with aflibercept of
1–4.5%. In all cases reported in our study, the clinical finding of
inflammation resolved, and no cases of intraocular inflammation
with vascular occlusions were observed. We believe that these
safety data coupled with the safety observations across the ongoing
Phase 3 studies continue to suggest a safety profile for KSI-301
comparable to aflibercept", said Dr. Ehrlich.
Dr. Ehrlich continued, "We thank the participants, clinicians,
site staff and the Kodiak team who participated in this trial and
who continue to participate in the ongoing and important KSI-301
clinical program."
Full results from the study are expected to be presented at a
future medical symposium.
Conference Call and Webcast
Kodiak will host a conference call and webcast to discuss the
results of the Phase 2b/3 study
today, February 23 at 8:00 a.m.
ET. To access the live call by phone, please dial 323-794-2590 and
provide the conference ID 2311990. A live audio webcast of the
event and accompanying slides may also be accessed through the
"Events and Presentations" page of the "Investors and Media"
section of the company's website. A replay of the webcast will be
available for 30 days following the event.
About KSI-301
KSI-301 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 KSI-301 is to develop a new first-line agent 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. The KSI-301 clinical program is designed
to assess KSI-301'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 DAZZLE and DAYLIGHT pivotal
studies in patients with treatment-naïve wet AMD, GLEAM and GLIMMER
pivotal studies in patients with diabetic macular edema, and the
BEACON pivotal study in patients with retinal vein occlusion are
anticipated to form the basis of the Company's initial BLA to
support potential approval and commercialization in multiple
indications and with a full range of labeled and reimbursable
dosing frequencies in each indication. An additional Phase 3
pivotal study, GLOW, in patients with non-proliferative diabetic
retinopathy is also underway. The global KSI-301 clinical program
is being conducted at 150+ study sites in more than 10 countries.
Kodiak is developing KSI-301 and owns global rights to KSI-301.
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
KSI-301 in patients with treatment-naïve macular edema due to
retinal vein occlusion (RVO), including both branch and central
subtypes. Patients are randomized to receive either intravitreal
KSI-301 every eight weeks after only two loading doses or monthly
intravitreal aflibercept per its label, for the first six months.
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 KSI-301
for an additional six months on an individualized basis. The study
has enrolled over 550 patients worldwide. The primary endpoint is
at six months, and patients will be treated and followed for 18
months. 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 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 KSI-301 in patients with treatment-naïve wet AMD.
Patients are randomized to receive either KSI-301 on a monthly
dosing regimen or to receive standard-of-care aflibercept. The
study is expected to enroll approximately 500 patients worldwide.
The primary endpoint is at ten months, and the study is being
planned and executed to allow for inclusion of its results in the
initial BLA for KSI-301. The intent of this pivotal study is to
broaden KSI-301's potential product labeling, explore the potential
for improved treatment outcomes in certain patients with intensive
anti-VEGF treatment, and eliminate possible barriers to market
access and insurance reimbursement that have impeded or complicated
the commercial uptake of other anti-VEGF medications in the past.
We believe that pursuing a broad product label will provide
physicians with the flexibility, agency, and reimbursement
confidence required to consider KSI-301 treatment for all their
patients. 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 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 KSI-301 in patients with treatment-naïve
diabetic macular edema (DME). In each study, patients are
randomized to receive either intravitreal KSI-301 on an
individualized dosing regimen every eight to 24 weeks after only
three loading doses or intravitreal aflibercept every eight weeks
after five loading doses per its label. Each study is expected to
enroll approximately 450 patients worldwide. The primary endpoint
for both studies is at one year, and patients will be treated and
followed for two years. 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 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, KSI-301, 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
including KSI-501, our bispecific anti-IL-6/VEGF biopolymer
conjugate for the treatment of neovascular retinal diseases with an
inflammatory component, and 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.
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
anti-VEGF effect of KSI-301, the expected advances for treatment of
wet AMD represented by KSI-301, the anticipated safety profile for
KSI-301, the potential of our ABC Platform to significantly extend
treatment intervals in retinal disorders in a safe and convenient
manner, future development plans, including clinical objectives and
the timing thereof, anticipated design and benefits of planned
clinical trials, and the anticipated presentation of data;
potential for a single BLA submission in wet AMD, DME and RVO; the
potential for our products to obtain a product label in multiple
indications and with a full range of labeled and reimbursable
dosing frequencies in each indication; and the results of our
research and development efforts and our ability to advance our
product candidates into later stages of development.
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
KSI-301 product candidate may not continue or persist; the risk
that KSI-301 may not have the anti-VEGF effect or impact on the
treatment of wet AMD expected; cessation or delay of any of the
ongoing clinical studies and/or our development of KSI-301 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 KSI-301, including those related to
current and planned clinical studies, may be insufficient to
support regulatory submissions or approval; our research and
development efforts and our ability to advance our product
candidates into later stages of development may fail; any one or
more of our product candidates may not be successfully developed,
approved or commercialized; adverse conditions in the general
domestic and global economic markets, including the COVID-19
pandemic, which may significantly impact our business and
operations, including our clinical trial sites, as well as the
business or operations of our manufacturers, contract research
organizations or other third 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-Q, 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.
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