Complement 3 glomerulopathy (C3G) is a rare kidney disease caused by problems in the body's complement system, which normally helps fight infections. It damages tiny filters in your kidneys called glomeruli, which clean your blood. When these filters are damaged, proteins and blood cells can leak into your urine. Over time, this affects how your kidneys work and can lead to kidney failure and the need for dialysis.
Each person with C3G may have different symptoms. People may have many of the following symptoms or only a few.
- Cloudy, foamy, or dark pee (urine) that may be red, pink, or brown
- Swelling in your feet, hands, ankles, or around your eyes
- Joint pain
- High blood pressure
- Feeling tired or weak
- Frequent infections
- Eye problems
Treatment for C3G includes medicines such as angiotensin-converting enzyme (ACE) inhibitors or angiotensin II type-1 receptor blockers (ARBs) that control blood pressure and lower the amount of protein spilling into your urine. This may help slow down the progression of C3G. If you have high cholesterol, treatment with medicine to lower your cholesterol may slow down the time it takes for your C3G to get worse. Other treatment options may include glucocorticoids plus mycophenolate mofetil (MMF). These medicines suppress your immune system and may prevent relapses of C3G in some people.
Iptacopan (Fabhalta) is the first medicine approved for C3G in adults to lower protein in the urine.
How Does Fabhalta Work for C3G?
Fabhalta is a medicine that blocks factor B of the alternative complement system, which is part of your immune system. Normally, this system helps your body fight infections. In C3G, this system becomes overactive and causes a protein called C3 to build up in the kidneys. This can lead to protein spilling into the urine (proteinuria), which may cause kidney damage over time. By blocking factor B, Fabhalta helps reduce protein in the urine.
How Should I Take This Medicine?
Fabhalta is an oral capsule that is swallowed whole and taken twice a day, 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.
How Was Fabhalta Studied for C3G?
A clinical study called APPEAR-C3G was done to see if Fabhalta was safe and effective, compared to a placebo, in 72 adults with C3G. The study did not include people with recurrent C3G after a kidney transplant. Most of the people in the study were male (64%). The average age was 28, and the study included White people (69%), Asian people (24%), and Hispanic or Latino people (9%). About half of the people in the study were taking glucocorticoids and/or MMF. Almost all of the people were taking a medicine called an ACE inhibitor or ARB.
In the first part of the study, people were randomly selected to take either oral Fabhalta or a placebo. Both were taken two times per day for six months. The placebo looked like Fabhalta but did not contain any medicine. Neither the people in the study nor the doctors knew who received Fabhalta or who got the placebo. After six months, all of the people in the study took Fabhalta for six more months. Those who took Fabhalta for the first six months continued for another six months. Those who took a placebo for the first six months took Fabhalta for the next six months of the study.
Everyone in the study was required to be vaccinated against Neisseria meningitidis, Streptococcus pneumoniae, and Haemophilus influenzae type B.
The main goal of the study was to see if Fabhalta could lower the amount of protein in the urine after six months of treatment. This was measured using 24-hour urine samples. The study also looked at changes in kidney function, disease activity, and fatigue.
What Benefits Were Seen?
People taking Fabhalta had greater decreases in the amount of protein in their urine, compared to those taking the placebo. After six months, people taking Fabhalta had a 35% decrease in protein in their urine from the beginning of the study, compared to those taking the placebo. This effect was maintained through 12 months of taking Fabhalta. When the people who took the placebo switched to Fabhalta, the decrease in protein in the urine after six months was similar to those who took Fabhalta. In the people who took Fabhalta for six months, kidney function stayed the same or improved, compared to those taking the placebo.
Your results may differ from what was seen in clinical studies.
What Can I Do to Manage Side Effects?
The most common side effects are nasal congestion, a runny nose, coughing, sneezing, and a sore throat. 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. To prevent these infections, reduce your exposure to germs by washing your hands and avoiding people who are sick. You must also have up-to-date vaccines, including pneumococcal and meningitis vaccines, at least two 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 find out the right vaccines and timing for treatment.
Call your health care provider right away if you have the following symptoms of infection.
- Fever with or without chills, chest pain, and coughing, 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 do blood tests to monitor your health and see how your body responds to the medication.
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 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 medicine called a CYP2C8 inducer, like rifampin, as it may decrease the levels of Fabhalta. It is not recommended to take Fabhalta with a strong CPY2C8 inhibitor, like gemfibrozil, because it can increase your risk of side effects from Fabhalta. Your health care provider will decide which treatment is best for all of your 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 find out 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 potentially 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 with Fabhalta and give you a safety card. This card should be carried with you during treatment and up to two 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 specialty pharmacies. The pharmacy must enroll in the REMS program and be familiar with the safety information. The pharmacy will confirm that your health care provider is enrolled in the program.
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 833-993-2242.