Novartis International AG / New analysis of Novartis Phase III
brolucizumab (RTH258) data reinforces superior reduction of retinal
fluid, a key marker of disease activity in nAMD . Processed and
transmitted by West Corporation. The issuer is solely responsible for
the content of this announcement.
-- Pre-specified analysis provides insight into maintenance treatment
effectiveness with like-for-like comparison of brolucizumab versus
aflibercept over entire week 36 to 48 treatment period
-- Retinal fluid was detected less often in patients treated with
brolucizumab 6 mg versus aflibercept between weeks 36 to 48
-- Regulatory submissions for brolucizumab on track for December 2018
Basel, 22 September 2018 - Novartis announced a new data analysis
showing that retinal fluid was detected less often in patients treated
with brolucizumab (RTH258) 6 mg versus aflibercept over four visits
between weeks 36 to 48[1]. Retinal fluid is a key marker of disease
activity in neovascular age-related macular degeneration (nAMD)[2]. The
data, from pre-specified secondary endpoints of the Phase III HAWK and
HARRIER trials[1], were presented at EURETINA 2018 as a follow-up to
data presented in November 2017.
The data show that brolucizumab 6 mg had superior fluid resolution
versus aflibercept over four visits during weeks 36 to 48. The 36- to
48- week analysis is noteworthy because it provides insight into the
effect of maintenance treatment, an important clinical focus for a
chronic disease like nAMD. Additionally, the analysis accounts for
dosing interval differences between the two medicines. Due to the unique
design of the HAWK and HARRIER trials, brolucizumab patients were dosed
at various intervals, namely q12w with some adjusted to q8w based on
disease activity. Aflibercept patients were dosed at q8w, per the label
at the time of trial initiation.
In the pre-specified secondary analyses for weeks 36 to 48, patients
treated with brolucizumab 6 mg in the HAWK and HARRIER trials had
significantly fewer visits in which intraretinal fluid (IRF)/subretinal
fluid (SRF) was observed. In HAWK, 47.5% of patients treated with
brolucizumab 6 mg q12w or adjusted to q8w had no visits in which IRF/SRF
was detected, compared to 42.5% of aflibercept patients (P=0.0012,
reflecting distribution across all visits during weeks 36 through
48)[1]. In HARRIER, 53% of patients treated with brolucizumab 6 mg had
no visits in which IRF/SRF was detected, compared to 45.5% of
aflibercept patients (P=0.0001, reflecting distribution across all
visits during weeks 36 through 48)[1]. Importantly, more than half of
brolucizumab 6 mg patients were maintained on q12w dosing until week 48.
"Retinal fluid is an important marker of disease activity and the need
for treatment. These new data give physicians even more insight into the
robustness of the 48 week anatomical findings and support the overall
impact brolucizumab has on key measures of retinal fluid, including
IRF/SRF, sub-retinal pigment epithelial fluid and central subfield
thickness," said Dirk Sauer, Development Unit Head, Novartis
Ophthalmology. "These results were noted even while more than half of
brolucizumab 6 mg patients were receiving treatment every 12 weeks at
week 48, further reinforcing our confidence in brolucizumab's superior
fluid resolution and supporting our goal of reimagining care for people
with nAMD."
As previously announced, HAWK and HARRIER achieved their primary
endpoints of non-inferiority in mean change in best corrected visual
acuity (BCVA) at week 48 with brolucizumab versus aflibercept. The key
pre-specified secondary endpoint of non-inferiority in mean change in
BCVA between weeks 36 and 48 was also met.
Brolucizumab safety was comparable to aflibercept with the overall
incidence of adverse events balanced across all treatment groups in both
studies[3]. The most frequent ocular adverse events (equal to or greater
than 5% of patients in any treatment arm) were reduced visual acuity,
conjunctival hemorrhage, vitreous floaters and eye pain[4]. The most
frequent non-ocular adverse events were typical of those reported in a
nAMD population; there were no notable differences between arms[4].
About brolucizumab (RTH258)
Brolucizumab (RTH258) is a humanized single-chain antibody fragment
(scFv) and the most clinically advanced, humanized single-chain antibody
fragment to reach this stage of development. Single-chain antibody
fragments are highly sought after in drug development due to their small
size, enhanced tissue penetration, rapid clearance from systemic
circulation and drug delivery characteristics[5],[6],[7].
The proprietary innovative structure results in a small molecule (26
kDa) with potent inhibition of, and high affinity to, all VEGF-A
isoforms[5],[8]. In preclinical studies, brolucizumab inhibited
activation of VEGF receptors through prevention of the ligand-receptor
interaction[5],[7],[8]. Increased signaling through the VEGF pathway is
associated with pathologic ocular angiogenesis and retinal edema[9].
Inhibition of the VEGF pathway has been shown to inhibit the growth of
neovascular lesions, resolve retinal edema and improve vision in
patients with chorioretinal vascular diseases[10].
About HAWK and HARRIER study design
With more than 1,800 patients across 400 centers worldwide, HAWK
(NCT02307682) and HARRIER (NCT02434328) are the first and only global
head-to-head trials in patients with nAMD that prospectively
demonstrated efficacy at week 48 using an innovative q12w/q8w regimen,
with a majority of patients on q12w immediately following the loading
phase[3],[11],[12]. Both studies are 96-week prospective, randomized,
double-masked multi-center studies and part of the Phase III clinical
development of brolucizumab[11],[12].
The studies were designed to compare the efficacy and safety of
intravitreal injections of brolucizumab 6 mg (HAWK and HARRIER) and 3 mg
(HAWK only) versus aflibercept 2 mg in patients with nAMD[11],[12]. In
both trials, patients were randomized to either brolucizumab or
aflibercept. Immediately following the 3-month loading phase, patients
in the brolucizumab arms received a q12w dosing interval with an option
to adjust to a q8w dosing interval based on masked disease activity
assessments at defined visits. Aflibercept was dosed bi-monthly
according to its label at the time of study initiation[3],[11],[12](*) .
Brolucizumab met the primary efficacy objective of non-inferiority
versus aflibercept in mean change in best-corrected visual acuity (BCVA)
from baseline to week 48 with high statistical significance[3].
Additionally, brolucizumab demonstrated superiority in three secondary
endpoints considered key parameters of nAMD: central subfield retinal
thickness, retinal fluid (intraretinal fluid and/or subretinal fluid)
and disease activity[3]. These results were achieved while a majority of
brolucizumab patients-56% in HAWK and 51% in HARRIER-were maintained on
a q12w dosing interval immediately following the loading phase through
week 48[3].
About neovascular age-related macular degeneration (nAMD or wet AMD)
nAMD is the leading cause of severe vision loss and legal blindness in
people over the age of 65 in North America, Europe, Australia and Asia,
impacting an estimated 20 to 25 million people worldwide[13],[14]. nAMD
occurs when abnormal blood vessels form underneath the macula, the area
of the retina responsible for sharp, central vision. These blood vessels
are fragile and leak fluid, disrupting the normal retinal architecture
and ultimately causing damage to the macula[15],[16],[17].
Early symptoms of nAMD include distorted vision or metamorphopsia and
difficulties seeing objects clearly[18]. Prompt diagnosis and
intervention are essential. As the disease progresses, cell damage
increases, further reducing vision quality. This progression can lead to
a complete loss of central vision, leaving the patient unable to read,
drive or recognize familiar faces[15]. Without treatment, vision can
rapidly deteriorate[19].
About Novartis in ophthalmology
For more than 70 years, patients, caregivers and healthcare providers
worldwide have looked to Novartis for state-of-the-art treatments in eye
diseases. We continue to invest in science as well as in strategic
alliances to help ensure patients have access to screening, diagnosis,
and our eye medicines. Our commitment to vision extends globally across
ages, from premature infants to seniors, from rare diseases to those
affecting millions, from eye drops to gene therapies. Our aspiration:
reimagining eye care to help everyone see possibilities.
Disclaimer
This press release contains forward-looking statements within the
meaning of the United States Private Securities Litigation Reform Act of
1995. Forward-looking statements can generally be identified by words
such as "potential," "can," "will," "plan," "expect," "anticipate,"
"look forward," "believe," "committed," "investigational," "pipeline,"
"launch," or similar terms, or by express or implied discussions
regarding potential marketing approvals, new indications or labeling for
the investigational or approved products described in this press release,
or regarding potential future revenues from such products. You should
not place undue reliance on these statements. Such forward-looking
statements are based on our current beliefs and expectations regarding
future events, and are subject to significant known and unknown risks
and uncertainties. Should one or more of these risks or uncertainties
materialize, or should underlying assumptions prove incorrect, actual
results may vary materially from those set forth in the forward-looking
statements. There can be no guarantee that the investigational or
approved products described in this press release will be submitted or
approved for sale or for any additional indications or labeling in any
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