Worldwide, the number of people with AMD is predicted to reach 288 million by 2040 (1). With a rapidly aging population, the number of people with AMD is only expected to rise. Though it’s true that there is a growing number of available therapeutic options, they have had limited impact on the long-term benefits for many patients. Currently, the most popular therapeutic options lie in dietary supplements, intravitreal injections, and laser treatments – all of which slow the progression of the disease. But none can stop AMD in its tracks.
Prevention, early detection, and effective treatment options are all needed to fully address the challenge of AMD. But here, we look at some new therapies that focus on incremental and subtler structural or functional degeneration with a view to yielding more sustained improvements or preservation of vision in dry AMD (see Table 1).
Type of therapy | Example(s) |
|---|---|
Neuroprotection | Elamipretide (Stealth) Risuteganib (Allegro) |
Reduction of toxic accumulation | GAL-101 (Galimedix) ALZ-801 (Alzheon) |
Modulation of the visual cycle | ALK-001 (Alkeus) |
Stem cells | HESCs (Lineage Cell Therapeutics, Regenerative Patch Technologies) Human retinal progenitor cells (iCyte) |
Inflammation suppression | ANX007 (Annexon) APL-2 (Apellis) (2) |
Table 1. Novel methodologies currently in development to treat dry AMD.
New endpoints
The latest innovations in AMD endpoints signal big changes in how the disease will be treated in the future. R&D dedicated to the development of novel endpoints can assist in identifying metrics that translate into an improved quality of life for patients, and its importance cannot be understated – especially in conditions such as AMD, where decreased visual function is sometimes not spotted on traditional measures of visual acuity.
The relevance of functional endpoints is becoming increasingly apparent in early evaluation for early-to-intermediate AMD. And it will be important to develop an understanding of the status and future direction of these solutions in relation to the vision loss caused by the condition. In Table 2, we outline several visual function endpoints that can more sensitively assess the real-world effects of early AMD versus the more conventionally used visual acuity charts.
Table 2. Visual function endpoints and real world effect
Functional Endpoint | Description |
|---|---|
Contrast sensitivity | Based on the ability to perceive objects against their background. Can be assessed as a function of spatial frequency or at various rates of motion or flicker, which are temporal frequencies. |
Reading speed | Reading is a valued activity and seriously impacted by AMD. |
Microperimetry | Perimetry that incorporates high-resolution testing of the macula in real-time, compensating for various eye movements. |
Dark adaptation | Decreased in patients with AMD, often before changes in visual acuity (3). |
Ora-VCF (Variable Contrast Flicker) Contrast Test & Low Luminance Tablet Reading Test | Combines contrast sensitivity, flicker fusion, and reading speed. Can detect visual deficits in patients with mild-moderate AMD and NPDR by detection of early visual dysfunction (4). |
The need for more patient-centered trials
New therapeutic targets and new endpoints certainly paint a rosier picture for the future. But we also need to address the thorny issue that stands in the way of getting treatments to patients: the clinical trial.
A patient-first clinical trial strategy is crucial to the future of standard patient care – but it also benefits clinical sites and therapy developers, while better serving the needs of trial participants with progressive conditions such as AMD.
As scientists, investigators, clinicians, and researchers, we know we must put the patient at the center of everything that we do. But how? Here are a few thoughts for consideration:
Conduct patient panels to identify how to make the protocols less burdensome (particularly regarding what tests are being administered and the number of visits necessary) and understand how to best support patients on their journey.
Develop patient-facing materials that consolidate important information in one place to address their needs.
Engage with patients throughout the entire clinical trial process in a compassionate and empathetic manner so that they feel involved. Remind them why they are taking part in a research study and make sure they feel appreciated for being part of the trial.
Optimize relationships with the investigators and monitors, particularly to reassure patients that all possible safety procedures are in place to ensure the risk of harm is mitigated.
It is widely known amongst industry professionals that patient participation in clinical research is extremely low; estimates suggest that just 3 percent of patients take part in a clinical trial. Retention is also an issue. And all these factors, combined with the complications brought on by the recent pandemic (e.g., increased staff turnover), put even more pressure on trials across all sectors. But that makes them no less critical. And so, increasing awareness and understanding of clinical trials is a top priority.
Industry members, physicians, sponsors, researchers, ophthalmic professionals, and healthcare practitioners all need to play their part, emphasizing the extraordinary value of clinical trials during interactions with patients. Presented with the right opportunity, an educated patient is much more likely to participate in research and thus contribute to the more rapid development of therapies that may benefit them and others with the same condition.
As well as being directly valuable to patients, clinical trial advocacy gives healthcare providers an opportunity to share pathways for alternative care and support and educate patient communities.
These advocacy efforts can include:
Patient-led initiatives to raise awareness of the clinical options available, increase patient involvement in research, and provide innovative care options.
Easy access to information from healthcare professionals to assist in broader education and an understanding of the conditions that surround degenerative eye diseases.
A true patient-first focus, which can help facilitate learnings from shared experiences to provide assurance and valuable insight for patients living with these debilitating conditions.
Whatever the approach, creating a clear pathway for clinical research holds the key to improving the patient experience.
The path to the patient
We have made progress – but there is a long way to go. Though we need new therapies to tackle unmet needs (for example, early-to-intermediate dry AMD and less frequent intravitreal injections), we cannot rely solely on therapeutic development. As we’ve highlighted above, exploring and validating functional endpoints and meeting actual patient needs – during clinical trials and down the road – are essential for success.
Strategies that enhance patient well-being, increase access to education, and raise the level of support provided by the organizations involved in the design of clinical trials will all boost patient enrolment and retention.
By ticking these boxes – better therapies, better endpoints, better trials – we’ll see faster translation from pre-clinical research to accessible treatment and, ultimately, a brighter future for all patients with AMD.
References
- T D L Keenan, Adv Exp Med Biol, “Age-Related Macular Degeneration: Epidemiology and Clinical Aspects,” 1256, 1 (2021). PMID: 33847996.
- Retina Today, “Retina Pipeline: A View Into Ongoing Innovation Dry AMD” (2022). Available at: shorturl.at/avBL6.
- LA Lesmes et al., “Visual Function Endpoints to Enable Dry AMD Clinical Trials,” Drug Discov Today Ther Strateg, 10, 43 (2013). PMID: 32863843.
- Ora, “Ora-VCF Contrast Test: Dry AMD Model” (2019). Available at: shorturl.at/ginR3.
