Study targets potential treatment for nAMD


HAWK, HARRIER treatment and study data

This article was reviewed by Chirag D. Jhaveri, MD

Editor’s Note: On Oct. 8, 2019, Novartis announced that the FDA approved brolucizumab injection (Beovu), also known as RTH258, for the treatment of wet age-related macular degeneration (AMD). The approval makes brolucizumab the first FDA approved anti-VEGF to offer both greater fluid resolution versus aflibercept and the ability to maintain eligible wet AMD patients on a three-month dosing interval immediately after a three-month loading phase with uncompromised efficacy, according to a prepared statement.


Analyses of data collected in phase III clinical trials investigating brolucizumab (Novartis) for the treatment of neovascular age-related macular degeneration (nAMD) provide further evidence that better disease control measured by less fluctuation of OCT-measured fluid is associated with better vision outcomes.

The research demonstrated a link between stability of central subfield thickness (CST) and having a dry retina, according to Chirag D. Jhaveri, MD. “Increased retinal thicknes s and fluid identified by OCT in any space in the retina in an eye with nAMD is an indication of active disease for which anti-VEGF therapy may be warranted,” said Dr. Jhaveri, private practice, Retina Consultants of Austin, Austin, TX, and clinical assistant professor of ophthalmology, Dell Medical School, the University of Texas at Austin. “Although fluid resolution correlates with vision improvement, the magnitude of the improvement is patient specific.”

Related: Decreasing burden of nAMD therapy 

According to Dr. Jhaveri, recent analysis of data from the CATT and IVAN trials found that fluctuation of CST in eyes with nAMD treated with antiVEGF therapy was another factor predicting the vision outcome.

“The results of our post-hoc analysis of data from the brolucizumab trials parallel the finding from CATT and IVAN,” he said. “In addition, we showed that increasing fluctuation in fluid was associated with an increased proportion of visits where retina drying was not achieved.”

The analyses of CST fluctuation associations used data from 96 weeks of follow-up in the HAWK and HARRIER trials and included only patients who had more than three CST observations. HAWK randomized patients 1:1:1 to brolucizumab 3 mg, brolucizumab 6 mg, or aflibercept 2 mg, and HARRIER compared brolucizumab 6 mg against aflibercept.

All treatments were initiated with a loading phase in which patients received three doses at monthly intervals.

Thereafter, brolucizumab was administered every 12 weeks with an option to adjust to dosing every eight weeks based on predefined disease activity assessments. After the loading phase, aflibercept was administered on a fixed schedule every eight weeks.

Related: Brolucizumab: Next-generation of anti-VEGF therapy?

Retinal thickness fluctuation for each patient was quantified by calculating the standard deviation of the individual’s standardized CST. Patients were pooled from both studies and divided into quartiles based on CST fluctuation. Each quartiles included 444 patients, and they were defined by the following values: <27 μm, 27-44 μm, 44-68 μm, and ≥68 μm.

The data showed that the mean BCVA gain at the end of the study decreased progressively across the four quartiles moving from the group with the lowest CST fluctuation to the group with the highest variability (+10.3, +8.8, +6.9, and +2.1 letters, respectively).

“The mean vision gain from baseline among patients in the quartile with the greatest amount of fluctuation was eight letters less than in the reference group in the lowest quartile, which parallels the finding from the CATT and IVAN analysis,” Dr. Jhaveri said.

Related: OCTA may be harbinger of anti-VEGF effiicacy 

Dr. Jhaveri said that a separate analysis was done to investigate whether there was a correlation between fluid presence after the loading phase and CST variability. CST standard deviation from week 12 to week 96 was calculated for each patient and used to divide the population into new quartiles.

The analyses were done separately for HAWK and HARRIER patients. Results showed eyes in the quartile with the least CST variability had the least amount of visits with fluid.

Those with the most fluctuations in CST had the most amount of visits with fluid.

“The findings indicate that a more stable retina with less CST variability is associated with a drier retina in addition to better BCVA gains,” Dr. Jhaveri said. 

Chirag D. Jhaveri, MD
Dr. Jhaveri is on the advisory board for Allergan and is a consultant for Genentech and Novartis. 

Read more by Cheryl Guttman Krader 

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