Press Release: New Novartis Phase III data for brolucizumab demonstrate reliability of 12-week treatment interval

Novartis International AG / New Novartis Phase III data for brolucizumab

demonstrate reliability of 12-week treatment interval. Processed and

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-- Patients identified for brolucizumab 12-week treatment interval in Phase

III HAWK and HARRIER trials had an 87% and 83% probability of

successfully continuing on a 12-week interval through week 48

-- Predictability data increase confidence in reliability of brolucizumab

12-week dosing regimen and potential of a simplified treatment plan

Basel, April 30, 2018 - Novartis announced new positive brolucizumab

(RTH258) data in neovascular age-related macular degeneration (nAMD)

from a pre-specified secondary analysis of the Phase III HAWK and

HARRIER trials. The findings showed that patients assessed as

appropriate for a 12-week treatment frequency during the first 12-week

cycle after loading could reliably stay on that quarterly interval

through week 48. This is the first time a high level of reliability has

been prospectively demonstrated for a pre-specified secondary endpoint

of a 12-week dosing interval with an anti-vascular endothelial growth

factor (VEGF) therapy in Phase III trials. These additional data were

presented at the Association for Research in Vision and Ophthalmology

(ARVO) 2018 Annual Meeting, in a follow-up to data presented in November

2017 at the American Academy of Ophthalmology.

The new findings showed that brolucizumab 6 mg patients who were

suitable for 12-week treatment intervals during the first 12-week cycle

after the loading phase had an 87% (HAWK) and 83% (HARRIER) probability

of remaining on this quarterly treatment interval through week 48. The

ability to reliably assess the likelihood of patients remaining on

quarterly dosing could help physicians and patients better manage,

personalize and optimize treatment plans.

"The ability to quickly identify patients who can maintain a 12-week

interval has the potential to simplify treatment plans for nAMD patients,

" said Glenn J. Jaffe, M.D., Chief of Retinal Ophthalmology, Duke

University, and an author of the presentation. "These robust data may

offer physicians confidence that when 12-week dosing with brolucizumab

is initially successful, there is high probability that the patient will

maintain this interval through the first year of treatment."

"HAWK and HARRIER previously demonstrated non-inferiority in the primary

endpoint of visual acuity and superiority in several secondary endpoints

assessing key anatomical outcomes versus aflibercept, with a majority of

brolucizumab patients maintained on an every-12-week dosing interval

following the loading phase through week 48[1]," said Dirk Sauer,

Development Unit Head, Novartis Ophthalmology. "Here we show that

success early on with brolucizumab appears strongly predictive of the

ability of these patients to successfully maintain this 12-week

treatment interval[2] through week 48. We look forward to continuing to

advance brolucizumab through regulatory approvals as a welcome new

option for treatment of nAMD, which is a leading cause of blindness."

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 (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 an 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[1],[5],[6].

The proprietary innovative structure results in a small molecule (26

kDa) with potent inhibition of, and high affinity to, all VEGF-A

isoforms[1],[7]. In preclinical studies, brolucizumab inhibited

activation of VEGF receptors through prevention of the ligand-receptor

interaction[1],[5],[6],[7]. Increased signaling through the VEGF pathway

is associated with pathologic ocular angiogenesis and retinal edema[8].

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[9].

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[10]. Both studies are 96-week prospective, randomized,

double-masked multi-center studies and part of the Phase III clinical

development of brolucizumab[10],[11].

The studies were designed to compare the efficacy and safety of

intravitreal injections of brolucizumab 6 mg and 3 mg (HAWK only) versus

aflibercept 2 mg in patients with nAMD[10],[11]. 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[10],[11].

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[2].

Additionally, brolucizumab demonstrated superiority in three secondary

endpoints considered key markers 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-57% in HAWK and 52% 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[12],[13]. 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[14],[15],[16].

Early symptoms of nAMD include distorted vision or metamorphopsia and

difficulties seeing objects clearly[17]. 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[14]. Without treatment, vision can

rapidly deteriorate[18].

About Novartis in ophthalmology

Novartis is a leading ophthalmology company, with therapies that treat

both front and back of the eye disorders, including retina diseases,

glaucoma, dry eye and other external eye diseases. In 2016,

approximately 200 million patients worldwide were treated with Novartis

ophthalmic products.

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April 30, 2018 16:05 ET (20:05 GMT)