Breaking News
September 24, 2018 - New nanoplatform technology may reverse drug-resistance in renal cell carcinoma
September 24, 2018 - October 1918 marks the centenary of Spanish Flu that claimed more lives than World War I
September 24, 2018 - LGBT community reports more number of poor mental health days than general population
September 24, 2018 - New research suggests power of zebrafish as tool for cancer drug discovery
September 24, 2018 - New study finds height as possible risk factor for developing varicose veins
September 24, 2018 - Researchers compare weight loss results of online and in-person diabetes prevention program
September 24, 2018 - New HER2 PET Study Uses Affibody’s ABY-025 Tracer to Individualize Breast Cancer Treatment
September 24, 2018 - Drug combination offers more effective care for patients suffering miscarriage
September 24, 2018 - Tallness linked to varicose veins, Stanford study says
September 24, 2018 - For Heart Failure Patients, Mitral Valve Procedure Improved Outcomes
September 24, 2018 - Ecstasy drug makes octopuses more social
September 24, 2018 - Immediate compression therapy could cut risk of complications after deep-vein thrombosis
September 24, 2018 - Transcatheter mitral valve repair reduces mortality for patients with mitral regurgitation
September 24, 2018 - First intracranial aneurysm patients treated with BRAVO Flow Diverter after CE mark approval
September 24, 2018 - ‘Physicians of the mouth’? Dentists absorb the medical billing drill
September 24, 2018 - People more likely to believe those with confident tone of voice than with accent
September 24, 2018 - Harmony Biosciences Presents 5-Year Data On Pitolisant At International Narcolepsy Symposium
September 24, 2018 - Blood test may identify gestational diabetes risk in first trimester
September 24, 2018 - Height may be risk factor for varicose veins | News Center
September 24, 2018 - King’s commemorates opening of new NMR facility with one-day symposium
September 24, 2018 - Eisai receives approval for partial label change of DC Bead device for transcatheter arterial embolization
September 24, 2018 - High-resolution genomic map gives scientists unprecedented view of brain development
September 24, 2018 - Alexion announces positive results from Phase 3 PREVENT study of Soliris in patients with NMOSD
September 24, 2018 - First evaluation of benefits, harms of Alzheimer’s screening for family members of older adults
September 24, 2018 - Children of mothers using cannabis may start using it at an earlier age, finds study
September 24, 2018 - Gilead Sciences plans to launch authorized generic versions of Epclusa and Harvoni in the US
September 24, 2018 - Most patients who underwent transcatheter valve replacement experience prosthesis-patient mismatch
September 24, 2018 - Lumos acquires license for LUM-201 drug that promotes secretion of growth hormone
September 24, 2018 - New study provides basis for Air Canada to change its facial hair policy for aircrew
September 24, 2018 - Infant walkers lead to thousands of emergency visits for babies
September 24, 2018 - Genes predicting person’s height may provide clues about causes of varicose veins
September 24, 2018 - EPA Plan Will Maintain Carbon Emissions From Power Plants
September 24, 2018 - Characterizing pig hippocampus could improve translational neuroscience
September 24, 2018 - Element3 Health reports social and mental engagement play key role in overall health
September 24, 2018 - Paralympic medalists support Fight for Sight’s unique virtual event
September 24, 2018 - ADCETRIS drug receives approval in Japan as frontline treatment option for Hodgkin lymphoma
September 24, 2018 - Public awareness of urological conditions found to be alarmingly low across Europe
September 24, 2018 - Fitter Folks Suffer Milder Strokes: Study
September 24, 2018 - Novel botulinum toxin compound relieves chronic pain
September 24, 2018 - CHMP recommends approval of Gilenya for treatment of multiple sclerosis in children, adolescents
September 24, 2018 - National Friendly’s private medical insurance is a hit with women living in the South East
September 24, 2018 - Academics receive prestigious awards for achievements in blood pressure research
September 24, 2018 - Obese pregnant women can restrict weight gain safely with proper nutrition guidance
September 24, 2018 - CHMP adopts positive opinion of Takeda’s ALUNBRIG for treatment of ALK+ non-small cell lung cancer
September 24, 2018 - China NMPA approves LENVIMA for treatment of unresectable hepatocellular carcinoma
September 24, 2018 - A new approach for finding Alzheimer’s treatments
September 24, 2018 - USC research uncovers previously unknown genetic risk factor for dementia
September 24, 2018 - Study examining mental health among students finds significant disparities in treatment across race
September 24, 2018 - Breakthrough discovery paves way for future test to identify drowsy drivers
September 24, 2018 - Transcatheter mitral-valve repair in patients with heart failure
September 24, 2018 - Study opens new avenues for treatment of Laing distal myopathy
September 24, 2018 - Stroke Facts | cdc.gov
September 24, 2018 - Sarcolipin tricks muscle cells into using more energy, burning fat
September 24, 2018 - Enrollment in opioid controlled substance agreement reduces primary care visits
September 24, 2018 - UTA researchers patent new smart seat cushion technology that helps prevent painful ulcers
September 24, 2018 - Second HPV-Related Primary Cancers Common in Survivors
September 24, 2018 - How a virus destabilizes the genome
September 24, 2018 - Old letters provide insight into Spanish flu pandemic horror
September 23, 2018 - Smart textile-based soft robotic exosuit helps wearers save energy and traverse difficult terrain
September 23, 2018 - New research hub to drive radical change in development and manufacturing of vaccines
September 23, 2018 - AHA: For Hispanics, Neighborhood May Be Key Factor in Heart Disease Risk
September 23, 2018 - Excessive airway nerves tied to more severe asthma symptoms, study finds
September 23, 2018 - Study highlights need to remain vigilant in maintaining key infection control processes
September 23, 2018 - Novel therapeutic strategy for blood vessel related disorders, such as cancer and retinopathy
September 23, 2018 - New naturally occurring antibiotic found effective against Mycobacterium tuberculosis
September 23, 2018 - First-in-human phase 0 study shows clinically-relevant activity of new drug in glioblastoma
September 23, 2018 - Removing tobacco product display from shops reduced number of children buying cigarettes
September 23, 2018 - Random fraction of specialized immune cells leads the charge in battling invaders
September 23, 2018 - Few minutes of sprinting exercise may be as effective as longer exercise sessions
September 23, 2018 - Researchers use neutrons to make first direct observations of water in lipid bilayers
September 23, 2018 - Researchers demonstrate pre-clinical success for universal flu vaccine in new paper
September 23, 2018 - Study reveals surprising gaps in some HIV medical providers’ knowledge of ACA
September 23, 2018 - Oxehealth secures European medical device accreditation for vital signs measurement software
September 23, 2018 - HTN Tx Intensification Common Upon Discharge in U.S. Vets
September 23, 2018 - Fibre can strengthen the intestinal barrier
September 23, 2018 - New platform examines infectious pathogens that may spread from animals to humans
September 23, 2018 - Demographers create detailed color map of population aging in Europe
September 23, 2018 - New type of fatty acid can slow down overreactive immune system
September 23, 2018 - Innovative procedure could provide breakthrough in treating early-stage lung cancer
September 23, 2018 - Research finds drop in number of measles cases in the EU/EEA since March 2018
New Novartis Phase III data for Brolucizumab Demonstrate Reliability of 12-week Treatment Interval

New Novartis Phase III data for Brolucizumab Demonstrate Reliability of 12-week Treatment Interval

image_pdfDownload PDFimage_print

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.

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 market, or at any particular time. Nor can there be any guarantee that such products will be commercially successful in the future. In particular, our expectations regarding such products 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; global trends toward health care cost containment, including government, payor and general public pricing and reimbursement pressures; our ability to obtain or maintain proprietary intellectual property protection; the particular prescribing preferences of physicians and patients; general political and economic conditions; safety, quality or manufacturing issues; potential or actual data security and data privacy breaches, or disruptions of our information technology systems, 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 2017, the Group achieved net sales of USD 49.1 billion, while R&D throughout the Group amounted to approximately USD 9.0 billion. Novartis Group companies employ approximately 124,000 full-time-equivalent associates. Novartis products are sold in approximately 155 countries around the world. For more information, please visit http://www.novartis.com.

References

[1] Dugel P, et al. HAWK & HARRIER: 48-week results of 2 multi-centered, randomized, double-masked trials of brolucizumab versus aflibercept for neovascular AMD. Presented at: The American Academy of Ophthalmology 2017 Annual Meeting on November 10, 2017, New Orleans.
[2] Dugel P, et al. A Comparison of the Anatomical Efficacy of Brolucizumab and Aflibercept in Neovascular Age-related Macular Degeneration (nAMD): An Analysis over 16 Weeks of Matched Treatment in the HAWK and HARRIER Studies. Presented at: the Association for Research in Vision and Ophthalmology (ARVO) 2018 Annual Meeting, Honolulu, HI.
[3] Data on file.
[4] Escher D, et al. 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 (link is external). Accessed November 2017.
[5] Nimz EL, et al. Intraocular and systemic pharmacokinetics of brolucizumab (RTH258) in nonhuman primates. The Association for Research in Vision and Ophthalmology (ARVO) annual meeting. 2016. Abstract 4996.
[6] Gaudreault J, 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 (link is external).
[7] Tietz J, 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.
[8] Qazi Y, et al. Mediators of ocular angiogenesis. J. Genet. 2009;88(4):495-515.
[9] 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.
[10] ClinicalTrials.gov. Identifier NCT02307682. Available at https://clinicaltrials.gov/ct2/show/NCT02307682 (link is external). Accessed November 2017.
[11] ClinicalTrials.gov. Identifier NCT02434328. Available at https://clinicaltrials.gov/ct2/show/NCT02434328 (link is external). Accessed November 2017.
[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 (link is external). Accessed November 2017.
[15] NHS Choices. Macular Degeneration. Available at http://www.nhs.uk/Conditions/Macular-degeneration/Pages/Introduction.aspx (link is external). Accessed November 2017.
[16] National Eye Institute. Facts About Age-Related Macular Degeneration. Available at https://nei.nih.gov/health/maculardegen/armd_facts (link is external). Accessed November 2017.
[17] NHS Choices. Macular degeneration – Symptoms. Available at http://www.nhs.uk/Conditions/Macular-degeneration/Pages/Symptoms.aspx (link is external). Accessed November 2017.
[18] 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.

Source: Novartis

Posted: April 2018

Tagged with:

About author

Related Articles