Syfovre FAQs and next steps for dry AMD and geographic atrophy treatment

The UK’s Medicines and Healthcare products Regulatory Agency (MHRA) decision to reject the first potential treatment for GA, or late-stage AMD is undoubtedly a disappointing one for those living with the condition. But, what does the decision mean? We answer your questions.

What is geographic atrophy? 

Geographic atrophy (GA) is the medical term for late stage dry aged-related macular degeneration (AMD). It is called geographic atrophy because the damage to the macula appears as patches where the cells have died (atrophy) that look like islands on a map. 

The areas of cell death or ‘atrophy’ tend to develop initially away from the central area of the macula, called the fovea. The fovea is responsible for the highest quality vision. As the condition progresses the atrophy spreads and can start affecting the fovea, leading to more severe sight loss.  

Read more about geographic atrophy. 

What is Syfovre? 

Syfovre (pegcetacoplan) is a drug that has been developed to treat GA, or late-stage dry AMD. The drug needs to be injected into the eye (called an intravitreal injection) every month or every other month.  

How does Syfovre work? 

The complement system is a set of proteins that is part of the immune system (the body’s natural defences). In people with GA, the complement system is overactive, causing inflammation and damage to the cells of the macula, ultimately leading to cell death and consequent sight loss. 

The drug attaches to and blocks the C3 protein of the complement system. By blocking C3, Syfovre prevents activation of the complement system. This slows down the rate of progression.  

How effective is it? 

Syfovre is unable to restore vision or cure geographic atrophy. Instead the drug works by slowing the rate at which the areas of atrophy grow larger over time. In this way it is hoped that vision loss will be reduced and central vision maintained for longer.  

The OAKS and DERBY clinical trials concluded that treatment with Syfovre reduced the rate of progression of GA. However, the results showed that Syfovre did not lead to a change in how well the participants could see during their vision tests. 

How safe is it? 

Results from 12, 18 and 24-month time points in both clinical studies suggested that Syfovre showed a similar safety profile to other intravitreally injected medicines for AMD. However, patients receiving Syfovre developed wet AMD more frequently than patients receiving sham injections.  

Regulatory context

When was it approved in the USA? 

It was approved for use in the USA by the Food and Drug Administration in February 2023. Since then, it has been used to treat people with GA. 

Non-approval in Europe 

Why wasn’t Syfovre approved by the European Medicines Agency (EMA)?  

Although the studies showed that Syfovre slowed the growth of GA lesions, the EMA considered that this did not lead to clinically meaningful benefits for patients. It was noted that benefits of a treatment should have an impact on patients’ everyday functioning, and this was not demonstrated in the studies. In terms of safety, regular injections into the eye carry a significant risk of adverse events, including the development of other forms of AMD or inflammation in the eye, which could further worsen vision.  

Although the EMA recognises the unmet medical need for effective treatment for people with GA caused by AMD, its opinion was that the magnitude of Syfovre's effectiveness did not outweigh the potential risks. The Agency therefore concluded that a positive balance of the medicine's benefits and risks could not be established in the treatment of GA caused by AMD. 

Assessment in the UK

How do MHRA approve drugs? 

Before a new medicine can be given to patients in the UK, it needs to be assessed by the Medicines and Healthcare products Regulatory Agency (MHRA). The MHRA review the data and evidence on risks and benefits of the treatment and, where appropriate, issue marketing authorisations. This process can usually take around a year to complete. 

Why wasn’t Syfovre approved by the MHRA in the UK?  

We understand that the MHRA recognised the effect Syfovre has on the progression of the disease and the growth rate of the GA lesions. However, they were concerned that meaningful benefit for patients had not been demonstrated in terms of their ability to see and manage daily tasks during the trial periods. 

Potential treatments in trial

What is the situation with the other new drug Izervay? 

The drug Izervay (avacincaptad pegol) was approved by the Food and Drug Administration to treat GA in the USA in 2023. It is also under consideration for approval in the UK by the MHRA.  

It is not approved by the European Medicines Agency as the company, Astellas, withdrew its application after Syfovre was refused a marketing authorisation in Europe. News | Astellas Pharma Inc. 

What other treatments might become available for dry AMD in the future? 

Several new drugs are being assessed as potential treatments for GA. They are all at different stages of development but some have reached phase three, the final stage of clinical trials before the manufacturer seeks a marketing authorisation. A variety of approaches are being explored, including oral tablets, skin injections and eye injections. 

Recent research on AREDS supplements suggests they may be able to slow the progression of GA but this is still to be confirmed through a clinical trial. 

Why does it take so long to get new drugs to patients? 

Potential new drug treatments can arise from laboratory research on the disease or the drug may be being used to treat another health condition already.  

If it is a novel drug, it will need to be checked to ensure that it is safe to give to humans, before being assessed for safety and efficacy in a series of clinical trials. If it is a drug that is already authorised for another condition, it will still need to be proven to be effective for the new condition through testing in clinical trials.  

If a drug is shown to be both safe and effective at treating the condition in clinical trials, it then needs to be approved for use more widely. This process of testing and approval can take 10 –15 years from start to finish but is important to ensure that the benefit of the drug is proven and outweighs any side effects. 

How can I get involved in a clinical trial?  

Information on how to volunteer for clinical trials can be found on the Macular Society website.