Novartis RTH258 (brolucizumab) demonstrates robust visual gains in nAMD patients with a majority on a 12-week injection interval
(Thomson Reuters ONE) -
Novartis International AG /
Novartis RTH258 (brolucizumab) demonstrates robust visual gains in nAMD patients
with a majority on a 12-week injection interval
. Processed and transmitted by Nasdaq Corporate Solutions.
The issuer is solely responsible for the content of this announcement.
* RTH258 achieved the primary efficacy endpoint of non-inferiority to
aflibercept in mean change in BCVA from baseline to week 48[1],[2] in two
head-to-head pivotal Phase III studies[3],[4]
* 57% and 52% of patients receiving RTH258 6 mg in the respective trials were
maintained exclusively on a q12w interval immediately following the loading
phase and continuing through week 48[1],[2]
* In both studies overall ocular and non-ocular adverse event rates for RTH258
were comparable to aflibercept[1],[2]
Basel, June 20, 2017 - Novartis, the global leader in Ophthalmology, today
reported that RTH258 (brolucizumab) 6 mg met the primary and key secondary
endpoints in two Phase III studies, HAWK and HARRIER. RTH258 3 mg, evaluated in
HAWK, also met these endpoints. These pivotal studies enrolled more than 1,800
patients with neovascular age-related macular degeneration (nAMD) across 400
centers worldwide. The primary and key secondary efficacy endpoints were non-
inferiority of RTH258 to aflibercept in mean change in best-corrected visual
acuity (BCVA) from baseline to week 48, and average mean change over the period
of week 36-48, respectively.[3],[4] Both were met with highly significant p
values. RTH258 was generally well tolerated with overall ocular and non-ocular
(systemic) adverse event rates comparable to aflibercept.[1],[2]
RTH258 demonstrated long-lasting efficacy versus aflibercept dosed every eight
weeks. A majority of patients, 57% (HAWK) and 52% (HARRIER), were maintained
exclusively on a q12w (every 12 week) interval immediately following the loading
phase through week 48.[1],[2]
"These results clearly and convincingly demonstrate RTH258 has the potential to
reduce injection burden while providing excellent visual outcomes. Given our
legacy in developing medicines to preserve vision, we are pleased that RTH258
carries the promise of being the next major advancement for patients with nAMD"
said Vas Narasimhan, Global Head, Drug Development and Chief Medical Officer,
Novartis. "Based on these robust data, we are looking forward to working with
regulatory agencies to bring this pioneering treatment to patients."
Detailed analysis of the data is ongoing and will be presented at an upcoming
medical congress. RTH258 is a highly innovative single chain antibody that
enables much higher concentrations of antibody in the eye than approved
therapies. Given the complexity of the formulation, Novartis has invested to
ensure a competitive, low cost of goods formulation over the past 18 months to
maximize the long term value of RTH258. Novartis expects to complete the
pharmacokinetic study with the final manufacturing process to enable filing in
2018.
RTH258 has the potential to address the needs of patients with nAMD who would
benefit from a long-lasting, efficacious treatment with a less frequent dosing
regimen.[5]
About RTH258 (brolucizumab)
Designed specifically for the eye, RTH258 is the most clinically advanced,
humanized single chain anti-body fragment in development. The proprietary
innovative architecture results in a small molecule (26 kDa) with potent
inhibition of, and high affinity to all VEGF-A isoforms.[6],[7] Potential
benefits of the small size include better tissue penetration and rapid clearance
from the systemic circulation.[6],[8],[9]
In preclinical studies,[6],[7],[8],[9] RTH258 inhibited activation of VEGF
receptors through prevention of the ligand-receptor interaction. Increased
signalling through the VEGF pathway is associated with pathologic ocular
angiogenesis and retinal edema[10]. 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.[11]
About HAWK and HARRIER
With more than 1,800 patients across 400 centers worldwide, HAWK and HARRIER are
the first and only global head-to-head trials in patients with nAMD that
prospectively demonstrate efficacy with a pre-specifed injection interval of 12
weeks.[1],[2] Both studies are 96-week prospective, randomized, double-masked
multi-center studies and part of the Phase III clinical development of
RTH258.[3],[4]
The studies were designed to compare the efficacy and safety of intravitreal
injections of RTH258 6 mg and 3 mg (HAWK only) versus aflibercept 2 mg in
patients with nAMD.[3],[4] The primary efficacy objective of HAWK and HARRIER
trials was to confirm that RTH258 is non-inferior to aflibercept in mean change
in best-corrected visual acuity (BCVA) from baseline to Week 48.[3],[4]
Secondary endpoints include average mean change in BCVA from baseline over the
period week 36-48, the proportion of patients on a q12w interval at week 48 and
anatomical parameters.[3],[4]
In both protocols, patients were randomized to either RTH258 or aflibercept.
Immediately following the 3-month loading phase, patients in the RTH258 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.[3],[4]
RTH258 6 mg met the primary and key secondary endpoints in two Phase III
studies, HAWK AND HARRIER. RTH258 3 mg, evaluated in HAWK, also met these
endpoints. In both studies, these endpoints were met with highly significant
p.[1],[2]
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 and grow underneath the macula, the area of the retina
responsible for sharp, central vision. These blood vessels are fragile and leak
fluid and blood, disrupting the normal retinal architecture and ultimately
causing damage to the light sensitive cells.[14],[15]
Early symptoms of nAMD include distorted vision or metamorphopsia and
difficulties seeing objects clearly.[16] Prompt diagnosis and intervention are
essential. As the disease progresses cell damage increases, further reducing
vision quality. This 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 deteriorate within days.[17]
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, 200 million patients worldwide
were treated with Novartis ophthalmic products.
Disclaimer
The foregoing release contains forward-looking statements that can be identified
by words such as "prospective," "commitment," "potential," "looking forward,"
"above expectations," "ongoing," "will," "upcoming," "on track," "end of 2018,"
"can," "would," "in development," or similar terms, or by express or implied
discussions regarding potential marketing approvals for RTH258, or regarding
potential future revenues from RTH258. You should not place undue reliance on
these statements. Such forward-looking statements are based on the current
beliefs and expectations of management 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 RTH258 will be
submitted or approved for sale in any market, or at any particular time. Nor can
there be any guarantee that RTH258 will be commercially successful in the
future. In particular, management's expectations regarding RTH258 could be
affected by, among other things, the uncertainties inherent in research and
development, including clinical trial results and additional analysis of
existing clinical data; regulatory actions or delays or government regulation
generally; the company's ability to obtain or maintain proprietary intellectual
property protection; general economic and industry conditions; global trends
toward health care cost containment, including ongoing pricing and reimbursement
pressures; safety, quality or manufacturing issues, and other risks and factors
referred to in Novartis AG's current Form 20-F on file with the US Securities
and Exchange Commission. Novartis is providing the information in this press
release as of this date and does not undertake any obligation to update any
forward-looking statements contained in this press release as a result of new
information, future events or otherwise.
About Novartis
Novartis provides innovative healthcare solutions that address the evolving
needs of patients and societies. Headquartered in Basel, Switzerland, Novartis
offers a diversified portfolio to best meet these needs: innovative medicines,
cost-saving generic and biosimilar pharmaceuticals and eye care. Novartis has
leading positions globally in each of these areas. In 2016, the Group achieved
net sales of USD 48.5 billion, while R&D throughout the Group amounted to
approximately USD 9.0 billion. Novartis Group companies employ approximately
118,000 full-time-equivalent associates. Novartis products are sold in
approximately 155 countries around the world. For more information, please visit
http://www.novartis.com.
Novartis is on Twitter. Sign up to follow (at)Novartis at
http://twitter.com/novartis
For Novartis multimedia content, please visit www.novartis.com/news/media-
library
For questions about the site or required registration, please contact
media.relations(at)novartis.com
References
[1] Data on file.
[2] Data on file.
[3] ClinicalTrials.gov. Identifier NCT02307682. Available at
https://clinicaltrials.gov/ct2/show/NCT02307682. Accessed June 2017.
[4] ClinicalTrials.gov. Identifier NCT02434328. Available at
https://clinicaltrials.gov/ct2/show/NCT02434328. Accessed June 2017.
[5] Prenner JL, et al. Disease Burden in the Treatment of Age-Related Macular
Degeneration: Findings From a Time-and-Motion Study. American Journal of
Ophthalmology. 2015;160(4):725-731.e1.
[6] Escher D, Schmidt A, STeiner P, Maurer P, Weissgerber G. Single-chain
antibody fragments in ophthalmology. Oral presentation at EURETINA congress.
2015. Abstract. Available at: http://www.euretina.org/nice2015/programme/free-
papers-details.asp?id=4072&day=0 (accessed 16 May 2017)
[7] Tietz J, Spohn G, Schmid G, et al. Affinity and Potency of RTH258
(ESBA1008), a Novel Inhibitor of Vascular Endothelial Growth Factor A for the
Treatment of Retinal Disorders. IOVS. 2015; 56(7): 1501.
http://iovs.arvojournals.org/article.aspx?articleid=2331210.
[8] Nimz EL, Van't Land CW, Yanez JA, Chastain JE. Intraocular and systemic
pharmacokinetics of brolucizumab (RTH258) in nonhuman primates. The Association
for Research in Vision and Ophthalmology (ARVO) annual meeting. 2016. Abstract
4996. http://www.arvo.org/webs/am2016/sectionpdf/RC/Session_443.pdf
[9] Gaudreault J, Gunde T, Floyd HS, et al. Preclinical pharmacology and safety
of ESBA1008, a single-chain antibody fragment, investigated as potential
treatment for age related macular degeneration. ARVO Annual meeting abstract.
Invest Ophthalmol Vis Sci 2012;53:3025.
http://iovs.arvojournals.org/article.aspx?articleid=2354604
[10] Qazi Y, et al. Mediators of ocular angiogenesis. J. Genet.
2009;88(4):495-515.
[11] Kim R. Introduction, mechanism of action and rationale for anti-vascular
endothelial growth factor drugs in age-related macular degeneration. Indian J
Ophthalmol. 2007;55(6):413-415.
[12] Schmidt-Erfurth U, et al. Guidelines for the management of neovascular age-
related macular degeneration by the European Society of Retina Specialists
(EURETINA). Br J Ophthalmol. 2014;98:1144-1167.
[13] Chopdar A et al. Age related macular degeneration. BMJ.
2003;26(7387):485-488.
[14] World Health Organization. Priority eye diseases: Age-related macular
degeneration. Available at
http://www.who.int/blindness/causes/priority/en/index7.html. Accessed June
2017.NHS Choices. Macular Degeneration. Available at
http://www.nhs.uk/Conditions/Macular-degeneration/Pages/Introduction.aspx.
Accessed June 2017.
[15] National Eye Institute. Facts About Age-Related Macular Degeneration.
Available at https://nei.nih.gov/health/maculardegen/armd_facts. Accessed June
2017
[16] NHS Choices. Macular degeneration - Symptoms. Available at
http://www.nhs.uk/Conditions/Macular-degeneration/Pages/Symptoms.aspx. Accessed
June 2017.
[17] van Lookeren Campagne M, et al. Mechanisms of age-related macular
degeneration and therapeutic opportunities. J Pathol. 2014; 232(2):151-64. doi:
10.1002/path.4266.
# # #
Novartis Media Relations
Central media line: +41 61 324 2200
E-mail: media.relations(at)novartis.com
Eric Althoff Friedrich von Heyl
Novartis Global Media Relations Novartis Pharma Communications
+41 61 324 7999 (direct) +41 61 324 8984 (direct)
+41 79 593 4202 (mobile) +41 79 749 0286 (mobile)
eric.althoff(at)novartis.com friedrich.vonheyl(at)novartis.com
Novartis Investor Relations
Central investor relations line: +41 61 324 7944
E-mail: investor.relations(at)novartis.com
Central North America
Samir Shah +41 61 324 7944 Richard Pulik +1 212 830 2448
Pierre-Michel Bringer +41 61 324 1065 Cory Twining +1 212 830 2417
Thomas Hungerbuehler +41 61 324 8425
Isabella Zinck +41 61 324 7188
Media release (PDF):
http://hugin.info/134323/R/2114312/804427.pdf
This announcement is distributed by Nasdaq Corporate Solutions on behalf of Nasdaq Corporate Solutions clients.
The issuer of this announcement warrants that they are solely responsible for the content, accuracy and originality of the information contained therein.
Source: Novartis International AG via GlobeNewswire
Unternehmensinformation / Kurzprofil:
Datum: 20.06.2017 - 07:15 Uhr
Sprache: Deutsch
News-ID 548710
Anzahl Zeichen: 16032
contact information:
Town:
Basel
Kategorie:
Business News
Diese Pressemitteilung wurde bisher 386 mal aufgerufen.
Die Pressemitteilung mit dem Titel:
"Novartis RTH258 (brolucizumab) demonstrates robust visual gains in nAMD patients with a majority on a 12-week injection interval"
steht unter der journalistisch-redaktionellen Verantwortung von
Novartis International AG (Nachricht senden)
Beachten Sie bitte die weiteren Informationen zum Haftungsauschluß (gemäß TMG - TeleMedianGesetz) und dem Datenschutz (gemäß der DSGVO).
