Paroxysmal nocturnal hemoglobinuria (PNH) is a rare immune disease that causes your body to break down red blood cells when it should not. This disorder happens when there is a problem with certain cells in the bone marrow. In people with PNH, these cells do not work properly and create RBCs that are destroyed by the immune system too easily. When red blood cells are destroyed (also referred to as hemolysis), hemoglobin can be found in the urine (referred to as hemoglobinuria). Hemoglobin is a component of red blood cells that carries oxygen. People with hemoglobinuria may have urine that is dark in color or blood-colored. If hemoglobinuria occurs, it is usually most obvious in the morning.
The symptoms associated with PNH vary greatly from one person to the next. While hemoglobinuria is common, it may not always be noticeable. Another complication of PNH is an increased risk for development of blood clots, some of which can be life-threatening. In addition to the impact on red blood cells, other cells may also be affected, such as white blood cells (which help to fight off infections) and platelets (which help your blood to form clots).
Treatment of PNH targets the specific symptoms you are experiencing. The list below describes different treatment options and the symptoms they target. Your health care provider will help you to determine the best treatment for you.
- Androgen therapy. Androgens are male hormones that stimulate the bone marrow to produce red blood cells. Androgen therapy (for example, danazol) may help to improve the symptoms of anemia caused by hemolysis.
- Anticoagulants. These medicines prevent blood clots from forming. Some examples of anticoagulants that may be used in people with PNH are injectable medicines, like enoxaparin, or pills that can be taken orally (apixaban, dabigatran, edoxaban, rivaroxaban, or warfarin).
- Blood transfusions. People with low levels of blood cells may require blood transfusions. Red blood cell transfusions can help to correct anemia, while platelet transfusions can help to prevent or treat serious bleeding.
- Bone marrow transplant. This is a procedure where a person’s bone marrow is destroyed using chemotherapy, immunotherapy, or radiation therapy (or a combination of these), then replaced with healthy bone marrow. In people with PNH, healthy bone marrow usually comes from a donor with a similar genetic makeup to the person with PNH. It is transplanted into the person with PNH by an intravenous infusion. Bone marrow transplantation is the only cure for PNH. However, it can cause severe complications and even death and is reserved only for very severe cases of PNH.
- Complement inhibitors. These medicines target the part of the immune system that causes hemolysis of red blood cells. Examples of complement inhibitors used for PNH include Soliris (eculizumab) and Ultomiris (ravulizumab). These medicines work by slowing down the breakdown of red blood cells.
- Folic acid (folate). This vitamin supplement can help to support the body as it makes more red blood cells to try to compensate for those destroyed by hemolysis.
- Growth factors. Growth factors can help stimulate your bone marrow to produce different types of cells. Examples of growth factors that may be used in people with PNH are:
- Red blood cell growth factors. Erythropoietin is a growth factor made by the kidneys and stimulates the bone marrow to produce more red blood cells. Products containing a lab-made form of erythropoietin (for example, Aranesp, Epogen, and Procrit) can reduce the need for blood transfusions by increasing the number of red blood cells.
- White blood cell growth factors: Granulocyte-colony stimulating factor (G-CSF) is a white blood cell growth factor that stimulates the bone marrow to produce more granulocytes. Granulocytes are a type of white blood cell that help to fight certain infections.
- Immunosuppressants. Immunosuppressant drugs, such as antithymocyte globulin, cyclosporine, or eltrombopag, may be used to restore function of the bone marrow. However, these drugs will not have any effect on the genetic mutation that causes PNH.
- Iron supplements. People with hemolysis may develop iron deficiency. Iron supplements can help to replace iron lost in the urine.
- Steroids. Steroids (for example, prednisone) may help slow the breakdown of red blood cells. Long-term treatment with steroids can cause serious side effects. Your health care provider can help you to decide if steroids are right for you.
How Does Empaveli Work?
Empaveli blocks the third component of the complement system (C3) within the immune system. Your complement system is a part of the immune system that activates proteins to help your body heal from infections or injuries. In people with PNH, the complement system helps to slow down the breakdown of red blood cells. Other medicines target a different area of the immune system (complement C5). These medicines prevent hemolysis that happens inside of your blood vessels (called intravascular hemolysis).
Empaveli is different from these medicines because it blocks a different part of the immune system, which prevents both intravascular hemolysis and hemolysis that happens outside of the blood vessels, in areas such as the liver and spleen (extravascular hemolysis). Empaveli may be especially useful in people with PNH who continue to have anemia even after treatment with a C5 complement-targeting medicine.
How Do I Use Empaveli?
Empaveli comes as an injection solution that contains 1,080 milligrams of Empaveli in 20 mL of liquid. One vial of the medicine contains a single dose. A 1,080-milligram dose is used twice weekly. Your health care provider will monitor certain labs during your treatment, including lactate dehydrogenase (LDH). Lactate dehydrogenase is an enzyme in the blood that indicates that red blood cells are breaking apart. If your LDH level is too high, your health care provider may increase your dose of Empaveli to be used every 3 days.
Before you use Empaveli for the first time, your health care provider will show you how to use it. After you learn how to use Empaveli, you may be able to give it to yourself at home. Empaveli is used in one of two ways.
- By a pump, obtained from your health care provider, that infuses the medicine under your skin over 30-60 minutes through a needle that you insert.
- By a one-time injector system that you stick to your stomach that infuses the medicine under your skin over 30-60 minutes.
How Was Empaveli Studied for Treatment of PNH?
Empaveli was studied in two studies known as PEGASUS and PRINCE. In PEGASUS, Empaveli was compared to eculizumab, another treatment for PNH, in people who were already receiving treatment with eculizumab for at least 3 months. In PRINCE, Empaveli was compared to best supportive care (for example, symptom management with blood transfusions, steroids, or vitamins/supplements) in people who had not used any other treatment for PNH in the past 3 months. In both studies, Empaveli 1,080 milligrams was given twice weekly as an infusion under the skin. In PEGASUS, people in the study who received eculizumab were given the same dose that they were using before the start of the study.
The average age of people in the PEGASUS trial was 47-50. Most people in the trial were White (59%-64%). Other races that were represented included Asian (12%-18%), and Black (0%-5%). Additional races were not described. More than half of the people in the trial were female (56%-65%). At the start of the study, the average hemoglobin level was 8.7 g/dL. People enrolled in the trial had an average of about six blood transfusions in the year before the study. About one-third of people in the trial were also taking medicines to keep blood clots from forming (anticoagulants or antiplatelets) before and during the study.
People in the PRINCE trial had an average age of 42-49, and most were Asian (65%-89%), while 11%-26% were American Indian or Alaska natives, 0%-6% were Black or African American. There were no white people in the study. Other races were not described. At the beginning of the study, the average hemoglobin level was between 8.7-9.4 g/dL. In the year before the study, people enrolled had an average of four to five blood transfusions. Compared to the PEGASUS trial, fewer people were taking anticoagulants or antiplatelets before (17%-28%) and during (0%-9%) the study.
Both studies compared the effects of the treatments on hemoglobin levels. The PEGASUS trial looked at the change in hemoglobin level over time, while the PRINCE trial looked at hemoglobin stabilization. Hemoglobin stabilization was defined as the number of people who avoided a decrease in hemoglobin of more than 1 g/dL without needing a blood transfusion. The PRINCE study also compared the change in LDH between groups.
After finishing these studies, people could choose to be in a longer study for an additional 8 months. In the longer study, people were only given Empaveli 1,080 milligrams under the skin two to three times weekly. The longer study’s goal was to make sure Empaveli continued work and was safe over this longer period of time.
What Benefits Were Seen in the Studies?
In both the PEGASUS and PRINCE trials, people treated with Empaveli had better hemoglobin levels at the end of the study period compared to people treated with eculizumab or supportive care.
- In PEGASUS, hemoglobin increased by 2.37 g/dL in people who used Empaveli and decreased by 1.47 g/dL in people who used eculizumab.
- In PRINCE, 85.7% of people treated with Empaveli achieved hemoglobin stabilization compared to 0% of people who were treated with best supportive care.
- In PRINCE, LDH levels decreased by an average of 1,870 units/L in people who used Empaveli and decreased by 400 units/L in people who were treated with best supportive care.
In both studies, the side effects reported most often in people who used Empaveli were ones that the medicine is known to cause, such as increased infections and pain or redness where Empaveli is injected under the skin. Before you start taking Empaveli, your health care provider will make sure you are up to date with your vaccinations. If you are not up to date, you may be prescribed a course of antibiotics until you can receive those vaccinations. While you are using Empaveli, make sure to get enough sleep, eat a balanced diet, and wash your hands frequently. If you have pain where the medicine is injected, apply a warm or cool compress to the area for 15 to 20 minutes.
Findings from the longer study showed that Empaveli continued to be effective for treating PNH. No unexpected or concerning side effects were reported.
Your results may differ from what was seen in clinical studies.
What Should I Know About the Empaveli REMS Program?
Empaveli is only available through a restricted Risk Evaluation and Mitigation Strategy (REMS) program. The FDA requires REMS programs for some medicines that have serious safety concerns. These programs help to make sure that anyone prescribing, dispensing, or receiving the medicine is aware of the safety concern and that any measures needed to help the medicine be used safely are in place. In order to prescribe Empaveli, your health care provider will need to enroll in the REMS program. The REMS program requires your health care provider to tell you more about the serious risk of infections associated with Empaveli. They will also make sure that you have received all of the correct vaccines to minimize this risk. If you have not yet gotten the correct vaccines, they will make sure that you receive appropriate antibiotics, if needed.
Pharmacies that dispense Empaveli are also required to be certified through the Empaveli REMS program. They must also make sure that your doctor who prescribed Empaveli is certified through REMS. Your health care provider should give you information about which pharmacies you can use to get Empaveli.
As the person using Empaveli, you must learn more about the risk of serious infections associated with Empaveli from your health care provider. This discussion will include information about the need for certain vaccines, when antibiotics may be needed, and signs to look out for that may indicate a serious infection. When the drug is prescribed, you will be supplied with a Patient Safety Card that you should carry with you at all times during treatment and for 2 months after stopping treatment. This will help to let other people know that you are using Empaveli. It is important to carry the card with you even after you stop using Empaveli because your risk of getting a serious infection will last for several weeks after stopping it.
Is There Any Cost Assistance Available?
If you need support paying for Empaveli, the drugmaker may be able to help you. Check out their ApellisAssist program at empaveli.com/apellisassist-program/ to learn more about their patient assistance program or to ask questions about insurance coverage and out-of-pocket costs. You can also contact the drugmaker at 866-692-7527.