Evaluation of novel therapy endpoints in age-related macular degeneration supported by European Medicines Agency
The European public-private partnership consortium MACUSTAR has received a third Letter of Support from the European Medicines Agency (EMA) for its efforts in developing novel outcome measures for clinical trials evaluating treatments for the common eye condition age-related macular degeneration (AMD). The scientific advice by the agency was based on four-year study results of more than 600 Europeans with early stages of AMD who are at a high risk of developing visual impairment. EMA recognises the high quality and impact of the scientific outputs from the MACUSTAR project that may have impact on more than 200 million patients with AMD globally.
AMD leads to a slow but progressive decline in vision in people older than 55 with the deterioration of photoreceptor cells. In late AMD stages, this process results in a loss of function of the macula, the anatomical center of the retina responsible for highly resolved vision. Even though wet/neovascular AMD stages can be treated, visual function in atrophic manifestations of the disease cannot be restored once lost. Therefore, worldwide initiatives are targeting the development of treatments at an earlier stage of the disease to prevent irreversible visual loss.
The MACUSTAR study investigates which eye examinations predict disease progression and therefore represent potential endpoints for future interventional trials in intermediate AMD. These include high-resolution retinal imaging technologies, a detailed set of visual functional tests and instruments to evaluate patient-reported outcomes. In addition to conventional visual function tests, vision under reduced lighting conditions and different contrast settings is also assessed in the MACUSTAR study, since they typically show the most noticeable changes among all tests in early AMD stages.
At the core of MACUSTAR is an observational cohort study with 619 patients with early and intermediate AMD, spread out across 20 EVICR.net clinical centres, across seven European countries. MACUSTAR is the largest systematic study on intermediate AMD to date that measures functional and patient-relevant changes during the disease course, on top of imaging tests. The aim of the MACUSTAR consortium is to identify high-risk markers of progression from intermediate AMD to late AMD and to develop trial designs. For this purpose, the research consortium continues to seek support by regulatory authorities such as EMA.
While the MACUSTAR study is ongoing, participants have already completed up to four years of follow-up examinations. The resulting dataset generated very valuable insights into how vision and anatomy of the retina change with AMD. Researchers from the MACUSTAR consortium have analysed these four-year longitudinal data and found new and innovative ways to identify high-risk patients and design future clinical trials, for instance, based on optical coherence tomography and fundus-controlled perimetry. Using both tests, the MACUSTAR consortium first confirms the independent value of anatomical exams and specialised visual function tests in early AMD stages. This is particularly relevant given that current AMD classifications are purely based on structural AMD changes. The approaches newly developed within the MACUSTAR study can be directly employed in upcoming AMD studies and, therefore, serve AMD patients in the near future. Beyond this, the data analyses revealed that patient-reported outcomes, specifically the Vision Impairment in Low Luminance questionnaire (VILL) predict the development of an advanced disease stage over four years, which highlights the role of asking patients about their visual symptoms. These key four-year findings of the MACUSTAR study were supported during the recent independent assessment by EMA, which opens new possibilities to design clinical trials and eventually find treatments for early AMD stages. EMA specifically supported the value of both imaging-based measurements and visual function in predicting the prognosis of intermediate AMD, based on the MACUSTAR study data. This may enable better stratification of disease stages into subcategories in the future.
This support endorses MACUSTAR researchers to conduct more in-depth analyses of the study data, while the collection of longer follow-up data and the inclusion of other innovative tests is being continued. The MACUSTAR consortium looks forward to the 6-year follow-up available at the end of the clinical study period, which will permit MACUSTAR to further characterise iAMD on a longer time span and to fine-tune the new definition of clinical endpoints for future drug clinical trials in intermediate AMD.
Read the full Letter of Support
This project has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 116076. This Joint Undertaking receives support from the European Union’s Horizon 2020 research and innovation programme and EFPIA. A further funding from Bayer, Novartis and Roche enabled the study to be extended by three years.
