TTR Depleters

In ATTR amyloidosis, a protein in your blood called transthyretin (TTR) misfolds and clumps together. These clumps are called amyloid fibrils. The amyloid clumps build up in organs. This buildup can damage the heart, nerves, and other parts of the body.¹

Doctors have treatments that can help slow this process. Some drugs, called TTR stabilizers, help keep the TTR protein from breaking apart. Other drugs, called RNA silencers, tell the liver to make less TTR protein.²

But what about the amyloid clumps that are already stuck in the organs? Researchers are now testing a new type of treatment. These new drugs are called TTR depleters. Another term for them is amyloid fibril disruptors. Their goal is to clear out the amyloid clumps that have already formed.²

How do TTR depleters work?

TTR depleters are drugs designed to remove amyloid clumps from the body. They work in a completely different way from stabilizers or silencers.²

TTR depleters are a type of drug called a monoclonal antibody. You can think of them as "amyloid hunters" that are made in a lab. Here is how they work:^2,3

• They find the target – The antibodies are designed to hunt for and stick only to the misfolded TTR amyloid clumps. They ignore the normal, healthy TTR protein.
• They tag the target – When the antibody finds an amyloid clump, it sticks to it. This places a "tag" on the clump.
• They call for cleanup – This tag signals your body’s own immune system. It tells cleanup cells, called macrophages, to come and "eat" the tagged amyloid clump.

The main goal of TTR depleters is to clear amyloid out of organs like the heart. Scientists hope that removing these damaging clumps will help the organs work better. This is a new approach that is still being studied.^2-4

Examples of TTR depleters

It is important to know that TTR depleters are still investigational. This means they are being tested in clinical trials. They are not yet approved by the US Food and Drug Administration (FDA) to treat ATTR amyloidosis.^2-4

Two examples of TTR depleters currently in clinical trials are:^2,4,5

• Coramitug (PRX004) – This is a monoclonal antibody being studied for ATTR amyloidosis. It is designed to find and clear misfolded TTR clumps. An early Phase 1 study showed that the drug was safe and well-tolerated in patients. It is now in later-stage studies to learn more about its safety and how well it works.
• ALXN2220 – This is another monoclonal antibody. It is being tested in a large Phase 3 clinical trial. This study is looking at how well the drug works for people who have ATTR amyloidosis that affects the heart. This is also called ATTR cardiomyopathy, or ATTR-CM.

What are the possible side effects?

Because TTR depleters are still in clinical trials, doctors are still learning about their side effects. These drugs are usually given to a person through an IV. Some people may have an infusion reaction. This can happen while the drug is being given. It can feel like an allergic reaction.^4,5

Doctors in the clinical trials watch for all "treatment-emergent adverse events." This means any health problem that happens during the study. They also check to see if a person's body tries to fight the drug. This is called an "anti-drug antibody" response. In early trials, the drugs seem to be well-tolerated among patients.^4,5

Talk to your doctor about whether a TTR depleter is right for you and what to expect from a clinical trial. You should also call your doctor if you have any changes that concern you.

Other things to know

It is important to know that different types of amyloidosis have very different treatments. For example, you may hear about another monoclonal antibody drug called daratumumab. Daratumumab is an approved treatment for a different condition called AL amyloidosis. AL amyloidosis is caused by a different protein, not TTR. Therefore, daratumumab does not work for ATTR amyloidosis.³

Scientists are studying whether TTR depleters might one day be used alone or with these other drugs. Clinical trials are the only way to get access to these new treatments right now. Talk to your doctor to see if a clinical trial is a good option for you.^2-5

Before beginning any new treatment for ATTR amyloidosis, tell your doctor about all your health conditions and any other drugs, vitamins, or supplements you are taking. This includes over-the-counter drugs.