Paroxysmal nocturnal hemoglobinuria (PNH) is a rare blood disease due to a genetic defect, where your red blood cells (RBCs) do not have a protective layer of proteins. These missing proteins cause your immune system to attack your red blood cells and break them down too early, also called hemolysis. The hemolysis can happen inside (intravascular) and outside (extravascular) your blood vessels.
The most common symptoms of PNH are anemia and blood clots, which can be life-threatening. People with PNH may have many of the following symptoms or only a few.
- Feeling tired or weak
- Shortness of breath
- Headaches
- Irregular or fast heartbeat
- Belly pain
- Bruise easily
- Dark or brown pee (urine), especially overnight or in the morning
- Red, painful, and swollen area
Treatment for PNH includes blood transfusions, folic acid or iron for anemia, anticoagulants to prevent blood clots, and medicines that protect your RBCs from being attacked by your immune system. Your treatment will depend on how many symptoms you have and how severe they are.
The common medicines that protect against the attack by your immune system are IVs or shots, like eculizumab (Soliris) or ravulizumab (Ultomiris). These medicines inhibit the C5 portion of the complement system. They have shown to improve symptoms by stopping the intravascular hemolysis. But some people still have anemia while on treatment due to extravascular hemolysis still happening. Fabhalta, the first oral medicine, can further help reduce symptoms of PNH, even if the other medicines did not work.
How Does Fabhalta Work for PNH?
Fabhalta is a medicine that works to block factor B of the complement system, which is part of your immune system. When the complement system is working correctly, it helps fight off infections and helps keep you healthy. In PNH, this system is confused and attacks your own healthy RBCs. By inhibiting factor B, Fabhalta stops the attacks. This increases the number of healthy RBCs, which improves symptoms and reduces the need for blood transfusions.
How Should I Take This Medicine?
Fabhalta is an oral capsule that is swallowed whole, twice daily, with or without food. Do not open, break, or chew the capsules. If you miss a dose, take the missed dose as soon as you remember and continue with your regular schedule. Your health care provider will give you instructions on how to start treatment if you are changing from another medicine, like eculizumab or ravulizumab.
You must have up-to-date vaccines, including pneumococcal and meningitis vaccines, at least 2 weeks before starting treatment. If you have not been vaccinated and must start Fabhalta, you will receive the vaccines and start antibiotics. Your health care provider will determine the right vaccines and timing for treatment.
Do not stop taking Fabhalta without talking with your health care provider, even if your symptoms have improved. Stopping treatment may cause more breakdown of your RBCs. Your health care provider will determine the right time to stop and will monitor you closely for 2 weeks.
How Was It Studied for PNH?
Two studies were done to see if Fabhalta was safe and effective for treating PNH. Everyone in the studies had PNH with anemia.
People in the APPLY-PNH study were on another complement-inhibiting medicine, eculizumab (Soliris) or ravulizumab (Ultomiris), for at least 6 months before the study and had remaining anemia despite treatment. They either stayed on their current treatment or switched to Fabhalta. A little over half of the people were female, with an average age of 50. The average time since PNH diagnosis was over 10 years. The study included people from many countries, including the U.S. The average hemoglobin level was 8.9 grams per deciliter (g/dL), which is below normal and is one sign of anemia. About half of the people had at least one blood transfusion within 6 months of starting the study.
People in the APPOINT-PNH study had not been treated with another complement medicine and had signs of hemolysis. Everyone in the study was treated with Fabhalta. A little over half were male, with an average age of 42. The average time since PNH diagnosis was about 4 years. The average hemoglobin level was 8.2 g/dL, which is below normal and is one sign of anemia. Three-quarters of the people had at least one blood transfusion within 6 months of starting the study.
Everyone in both studies were required to be vaccinated against Neisseria meningitidis and recommended to be vaccinated against Streptococcus pneumoniae and Haemophilus influenzae type B. If hemoglobin levels were too low at specific times in the trial, people in the study would receive a blood transfusion.
Efficacy was measured by the following at the end of 24 weeks.
- Maintained an increase of hemoglobin levels of more than 2 g/dL
- Maintained a hemoglobin level of at least 12 g/dL
- Did not require a blood transfusion
What Benefits Were Seen in the Studies?
Changes in hemoglobin levels. People taking Fabhalta had greater increases in their hemoglobin levels, which may have resolved their anemia and improved their symptoms.
In the APPLY-PNH study, most (82.3%) of the people taking Fabhalta saw an increase of more than 2 g/dL in their hemoglobin levels. A little more than half (67.7%) had hemoglobin levels greater than 12 g/dL. This was compared with zero people taking the eculizumab (Soliris) or ravulizumab (Ultomiris).
In the APPOINT-PNH study, almost all (92%) of the people taking Fabhalta saw an increase of more than 2 g/dL in their hemoglobin levels. A little more than half (63%) had hemoglobin levels greater than 12 g/dL.
Blood transfusions avoidance. This was defined as not requiring a blood transfusion between weeks 2 and 24 of the studies. Not requiring a transfusion means that the people in the studies were able to maintain normal hemoglobin levels.
In the APPLY-PNH study, almost all (95%) of the people who took Fabhalta did not have a blood transfusion, compared to only half of the people taking eculizumab (Soliris) or ravulizumab (Ultomiris). In the APPOINT-PNH study, almost all (98%) the people did not have a blood transfusion.
Your results may differ from what was seen in clinical studies. You and your health care provider should determine if the benefits outweigh any potential risks.
Signs That Your Medicine Is Working
Fabhalta helps to protect your RBCs from being attacked by your immune system. This should increase the RBC and hemoglobin levels in your body. If your treatment is working, you may start to see the following improvements.
- Increased energy
- Reduced darkness or redness of your pee
- Improved appetite and less stomach area pain
- Reduced need for blood transfusions
- Easier to do normal daily activities
Improvements from treatment can be different for each person, so it is important to track your symptoms and review with your health care provider. Tell your health care provider if you do not think that your symptoms are improving after a few months.
How Can I Prevent and Manage Side Effects?
The most common side effects are headache, diarrhea, nausea, stomach pain, and rash. You may also have common cold symptoms and bacterial or viral infections.
There is also a risk of more serious infections due to specific bacteria, including Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae type B. These infections can be life-threatening if not treated quickly. The best way to prevent infection is to receive recommended vaccinations and reduce your exposure to germs by washing your hands and avoiding people who are sick. Call your health care provider right away if you have the following symptoms of infection.
- Fever with or without chills, chest pain and cough, a fast heart rate, a rash, or a hard time breathing
- Body aches with flu-like symptoms
- Clammy skin
- A persistent headache with fever, nausea, and vomiting, or a stiff neck or back
- Tiredness
- Confusion
- Vision changes
These are not all of the possible side effects. Talk with your health care provider if you are having symptoms that bother you. In the U.S., you can report side effects to the FDA at www.fda.gov/medwatch or by calling 800-FDA-1088 (800-332-1088). In Canada, you can report side effects to Health Canada at www.health.gc.ca/medeffect or by calling 866-234-2345.
What Monitoring or Blood Tests May I Need Before Starting and During Treatment?
Your health care provider may perform blood tests to monitor your health and assess how your body responds to the medication.
With PNH, checking blood levels of RBCs and hemoglobin is common with or without treatment. Before starting and during treatment, your health care provider will monitor these to see how you are responding and to help decide if a blood transfusion is needed.
Fabhalta may increase your cholesterol and triglycerides. Fasting blood checks of your cholesterol, including total cholesterol, LDL cholesterol, HDL cholesterol, and triglycerides, will be completed before starting and during treatment.
What Types of Interactions Can Happen?
Several medicines can affect the blood levels of Fabhalta. This may increase the risk of side effects or cause Fabhalta to not work as well. Your health care provider will closely monitor your response if you are taking a CYP2C8 inducer, like rifampin, as it may decrease the levels of Fabhalta. This means you may have more PNH symptoms. It is not recommended to take Fabhalta with a strong CPY2C8 inhibitor, like gemfibrozil. Your health care provider will decide which treatment is best for all conditions.
This is not a complete list of medicines that may interact with Fabhalta. Tell your pharmacist or other health care provider about all the prescription or over-the-counter (OTC) medicines, vitamins/minerals, herbal products, or other supplements you take or have recently taken. This will help them determine if there are any interactions, or if you need a dosage adjustment.
Getting Your Medicine: What to Expect
Fabhalta is part of the FDA’s Risk Evaluation and Mitigation Strategy (REMS) program. This is a program required by the FDA for medicines that have potential serious side effects. The goal is to inform you and your health care provider about the risks and how to manage and check for these symptoms during treatment. The drugmaker has a program to help support the process and may require that you use a specific pharmacy.
You can find out more at https://www.fabhalta-rems.com or by calling 833-993-2242. Here are some differences that you may expect.
Health care provider enrollment. Your health care provider will need to enroll in the REMS program and be certified to prescribe Fabhalta. This should only take a few days.
Safety information and monitoring. Your health care provider will give you an overview of the safety concerns and give you a safety card. This card should be carried with you during treatment and up to 2 weeks after stopping it. This is because your risk of serious infections may continue for a few weeks after your last dose of Fabhalta.
Before starting treatment, your health care provider will see if you have any symptoms of untreated serious bacterial infections or an incomplete vaccination history. During treatment, they will monitor you for signs and symptoms of serious bacterial infections.
Pharmacy access. Fabhalta is only available at approved pharmacies. The pharmacy must enroll in the REMS program and be familiar with the safety information. This should only take a few days. The pharmacy will review your vaccine history, confirm that your health care provider is enrolled in the program, and report any potential serious bacterial infections.
Cost assistance. There is a copay assistance program from the drugmaker that may allow you to pay $0 for your prescription. Whether you are eligible depends on whether you have prescription insurance and what type of insurance you have. You can find out more at https://support.fabhalta.com/ or by calling by calling 833-993-2242.