Exploring PNH Treatment Options: Finding Disease Control That Fits Your Life

Treatment for paroxysmal nocturnal hemoglobinuria (PNH) has changed a great deal. Today, there are more PNH treatment options than ever. Knowing how your options compare can help you talk about treatment with your hematologist.^1,2

How complement inhibitors work

In healthy blood, protective surface proteins act as a shield to keep red blood cells safe from the immune system. In PNH, red blood cells lack these protective proteins, leaving them vulnerable to attack by a part of the immune system known as the complement system.¹

The complement system operates through a step-by-step chain of immune reactions. Because PNH cells lack their protective shield, complement proteins attack them as the chain moves through its steps. Complement inhibitor medications work by blocking a specific step in the chain, stopping the destruction of red blood cells (hemolysis).¹

One goal of treatment with complement inhibitors is to increase your levels of hemoglobin, a protein in red blood cells that makes blood look red.^1,2

Types of red blood cell destruction (hemolysis)

When the complement system attacks unprotected red blood cells, 2 types of cell destruction (hemolysis) can occur:^1,2

• Intravascular hemolysis (IVH) – Red blood cells burst inside blood vessels. This type characterizes PNH. It causes symptoms like red, brown, or dark-colored urine.
• Extravascular hemolysis (EVH) – Red blood cells are tagged by the complement system and removed in the spleen and liver. Some people with PNH develop it.

C5 inhibitors: Blocking a late step

C5 inhibitors block a late step in the complement chain. This stops red blood cells from bursting inside blood vessels (IVH).¹

C5 inhibitors approved for PNH include:^1,3-7

• eculizumab (Soliris®) – Given by IV infusion.
• eculizumab-aeeb (Bkemv®) and eculizumab-aagh (Epysqli®) – Biosimilars of Soliris®, also given by IV. A biosimilar is highly similar to the original drug.
• ravulizumab-cwvz (Ultomiris®) – Given by IV, with more time between infusions. Approved for ages 1 month and older.
• crovalimab-akkz (PiaSky®) – Starts with an IV infusion, then shots under the skin. Approved for ages 13 and older, weighing at least 88 pounds.

The first C5 inhibitor changed PNH care. Blood clots fell by 92 percent compared with earlier years. Survival became close to that of people without PNH.¹

Still, some people on C5 inhibitors stay anemic. Depending on the definition, 10 to 30 percent develop symptom-causing extravascular hemolysis.¹

Upstream inhibitors: Acting earlier in the chain

Newer drugs act earlier, or upstream, in the complement chain. This can reduce both types of hemolysis. Some studies included people who stayed anemic on a C5 inhibitor. Switching to pegcetacoplan or iptacopan raised their hemoglobin levels. Many did not need transfusions. Adding danicopan to a C5 inhibitor also raised hemoglobin.^1,8-10

Experts have no proven way yet to pick the first drug for each person. Long-term data on upstream drugs are still being collected. Upstream inhibitors approved for PNH include:^1,8-10

• pegcetacoplan (Empaveli®) – A C3 inhibitor. It is infused under the skin with a pump or on-body device. Approved for adults.
• iptacopan (Fabhalta®) – A factor B inhibitor. It is a capsule taken by mouth. Approved for adults.
• danicopan (Voydeya®) – A factor D inhibitor taken by mouth. It is approved for adults with extravascular hemolysis. It is used only as an add-on to ravulizumab or eculizumab.

Pills mean no needles or infusion visits. But they must be taken every day, on schedule.

What are the possible side effects?

Side effects can vary depending on the specific drug you are taking. All complement inhibitors approved for PNH have a boxed warning. This is the strictest warning from the US Food and Drug Administration (FDA). They have this warning because they raise the risk of serious, life-threatening infections. You will need certain vaccines before starting. Each drug is available only through a special safety program.^3-10

Common side effects can include headache, respiratory infections, nausea, diarrhea, belly pain, and injection site reactions. Switching between crovalimab and another C5 inhibitor can cause a serious immune reaction.^3-10

Some people on upstream drugs have sudden flares of hemolysis, called breakthrough hemolysis. Serious infections have also been reported.¹

These are not all the possible side effects of complement inhibitors. Talk to your doctor about what to expect when taking complement inhibitors. You also should call your doctor if you have any changes that concern you when taking complement inhibitors.

Other treatments for PNH

Some people also need blood transfusions or blood thinners at times. A stem cell transplant is the only cure for PNH. But it has serious risks, and a matching donor is not always available.^1,2

Defining your personal goals of care

Survival is not the only goal. Think about what good control means in your daily life. Topics to discuss with your doctor include:2

• Energy – Can you do what you want to do most days?
• Transfusions – Do you still need them? How often?
• Lab results – Are your lab results what your doctor wants to see?
• Treatment routine – Do you prefer infusions, shots at home, or pills?
• Flexibility – How does your treatment fit with work, travel, and family plans?
• Side effects – Which risks feel acceptable to you?

Bring your top goals to your next visit and ask how each option could help.

Other things to know

Before beginning treatment for PNH, tell your doctor about all your health conditions and any other drugs, vitamins, or supplements you take. This includes over-the-counter drugs.

Treatments work differently for each person. Your hematologist can help you weigh the benefits and risks of each option. You do not have to make these choices alone.