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MACUSTAR receives third nod of approval from regulators

The European Medicines Agency issued a third letter of support for the development of new biomarkers and clinical endpoints for a condition that blurs vision and can lead to blindness.

30 January 2025
Person undergoing an eye exam. Image credit: People Images - Yuri A via Shutterstock.
Person undergoing an eye exam. Image credit: People Images - Yuri A via Shutterstock.

As we age, our eyesight often suffers. Age-related macular degeneration (AMD) is an eye disease that blurs central vision affecting older populations. If it progresses, it can cause blindness. More than 2.5 million patients in the EU are affected and late-stage AMD is the leading cause of blindness among the elderly in industrialised countries.

Up until now, the development of new treatments has been hampered by a lack of knowledge regarding why some people with the intermediate stage of the disease progress to late-stage AMD and become blind, and others don’t. There is a need for biomarkers to identify who will go on to develop late-stage AMD, and also a need for clinical endpoints that are capable of determining the effectiveness of new treatments under development.

The IMI MACUSTAR project has been developing tools that can help to accurately detect changes in eyesight over time, as well as measures and markers for assessing how well a treatment works. For instance, the team is assessing visual function tests that evaluate visual acuity under good and poor lighting conditions and tests that probe how fast patients can adapt to dim light conditions. The project has also validated a questionnaire to deliver insights into how living with AMD affects people’s quality of life.

In 2016, the MACUSTAR project requested qualification advice from the EMA on intermediate-stage AMD biomarkers. A first letter of support was sent on February 15 2018. The MACUSTAR consortium then carried out a study designed to assess the ability of the measures to discriminate between patients with different stages of AMD and the ability of the measures to reliably give the same result for the same patient measured twice. The results of thstudy were promising, and EMA provided positive feedback on the results in a second Letter of Support.

In 2023, MACUSTAR submitted a third request for qualification advice relating to biomarkers and novel clinical endpoint development in age-related macular degeneration. The consortium presented fresh/longitudinal data from 619 patients with intermediate AMD as well as from 34 people with early AMD who had undergone functional, structural and patient-reported outcome assessments every six months for a period of 3.5 years. During this time, 84 individuals progressed from iAMD to late AMD.

The request for advice focused on a discussion surrounding enrichment criteria – attempts by researchers to select study populations where the effects of a drug effect is more likely to be seen – as well as indication of iAMD and strategies for the evaluation of progression from iAMD to late-stage AMD.

The EMA’s Committee for Medical Products for Human Use (CHMP) agreed that the data presented by MACUSTAR supported an association between visual function deficits in iAMD and the likelihood that a person will develop AMD, an important step towards biomarker identification. The committee described the Vision Impairment in Low Luminance measure validated by MACUSTAR as promising for future trials.

Overall, the committee supported the goals and plans to carry out further research to develop trial enrichment criteria and trial endpoints for subjects with iAMD as described by MACUSTAR. Although the MACUSTAR project has ended, the work of the consortium is continuing thanks to industry funding.

Though IMI2 funding for MACUSTAR has ended, the longitudinal study will continue until 2027. This will allow a total of 6 years of patient follow-up data to be collected thanks to funding from EFPIA partners Bayer, Roche and Novartis, and will further support clinical endpoint and biomarker qualification in the future.

Frank Holz from the Universitatsklinikum Bonn, coordinator of the project, said "The MACUSTAR consortium has advanced a critical field with significant unmet clinical needs. Currently, no regulatory-accepted endpoints exist for interventional clinical trials for the intermediate stage of age-related macular degeneration. This gap underscores the importance of the strong collaboration between major academic ophthalmological clinical and research centers and leading industry partners with innovative programs, which continues to attract major attention within ophthalmology in Europe and beyond."

MACUSTAR is supported by the Innovative Medicines Initiative, a partnership between the European Union and the European pharmaceutical industry.