Hereditary angioedema (HAE) causes severe swelling attacks that are unpredictable, painful, and potentially life-threatening. People with this condition often use medicines that are injected into the body to help prevent these attacks from occurring. There are also injectable medicines that are used to help stop an attack that has already started.
In 2020, Orladeyo (berotralstat) became the first medicine that can be taken by mouth to help prevent swelling attacks in people with HAE.
How Does Orladeyo Work for Hereditary Angioedema?
HAE is a rare, inherited condition that is passed down from parents to their children. People with HAE do not have enough of a certain protein called complement component C1 esterase inhibitor (C1 inhibitor) in their bodies. This is caused by a mutation in the gene that codes for this protein.
C1 inhibitor helps to control how much fluid flows in and out of the body’s cells. When there isn’t enough C1 inhibitor present, fluid can build up outside of the blood vessels. This can block the normal flow of blood and fluid and lead to rapid and severe swelling. In people with HAE, this causes severe swelling attacks that happen without any warning and can last for a few days. On average, these swelling attacks happen about every 2 weeks, although some people may only experience them one or two times per year.
When the swelling occurs in the hands, feet, arms, legs, or face, the area will become hard and painful. Swelling can also occur in the gastrointestinal (GI) tract, which can cause nausea, vomiting, and stomach pain. If swelling occurs in the airway, it can become hard to swallow, speak, and breathe, which can be serious and life-threatening.
The key to managing HAE is to avoid certain triggers that can bring on a swelling attack and to take medicines that can help to prevent swelling attacks. There are also many medicines that can be used to treat swelling attacks once they occur, called “on-demand” treatments.
Orladeyo is one of the medicines that can help to prevent swelling attacks. The active ingredient in Orladeyo is called berotralstat. It blocks a substance in the body called kallikrein, which plays an important role in the process that leads to swelling. People who do not have enough C1 inhibitor have extra kallikrein, which increases the rate of swelling attacks. By blocking kallikrein from working, Orladeyo can decrease the number of swelling attacks in people with this condition.
How Do I Use It?
Orladeyo is available as capsules or pellets that are taken by mouth once daily with food. Unlike some of the other medicines used for HAE that treat swelling attacks after they happen, Orladeyo helps to prevent these attacks. If you are having an attack, do not treat it with Orladeyo. Instead, you should seek medical help right away or use an injected “on-demand” medicine that your health care provider has trained you to use during an attack.
It is very important that you do not take more than one dose of Orladeyo each day. Taking more than one dose per day can cause serious side effects, including a dangerous heart rhythm problem called QT prolongation.
If you are taking the oral pellets, they may either be placed in the mouth and swallowed right away with non-acidic liquid (such as water or milk), or they may be sprinkled onto soft, non-acidic food and swallowed right away. Non-acidic foods include creamed corn, mashed potatoes, pudding, and pureed bananas, carrots, and peas. You should not sprinkle the pellets onto acidic foods (such as applesauce or yogurt) because it can cause a bitter taste. The food you sprinkle it on should be at or below room temperature. If the pellets are not taken within 10 minutes of sprinkling on food, you should thow the dose away. Do not chew or crush the oral pellets, and eat a meal either right before or after your dose.
How Was It Studied for Treating HAE?
One study was done to see if Orladeyo was safe and effective for preventing swelling attacks in people with HAE. The people in this study were at least 12 years old, with an average age of about 40. Most of the people in the study (66%) were female and almost everyone in the study (93%) was White. The race of the other people in the study was not reported.
Everyone in the study had been diagnosed with HAE and had at least two swelling attacks in the 2 months before the study started. Most of the people in the study (70%) had more than two swelling attacks per month, on average. The rest of the people in the study did not have attacks quite as often, but they still had at least one per month, on average.
Orladeyo was compared with a placebo containing no medicine. There were two doses of Orladeyo taken during this study: 110 milligrams (mg) daily and 150 mg daily. Neither the people in the study nor the researchers knew which dose of medicine they were taking or whether they were taking the medicine or the placebo. Everyone in the study was expected to have an on-demand medicine for treating swelling attacks available throughout the study. If a swelling attack happened during the study, they were told to use their on-demand medicine the way that they normally would.
This study measured efficacy by counting the number of swelling attacks that people had during the first 6 months of the study.
What Were the Benefits?
Number of swelling attacks. Over 6 months, the people who took Orladeyo had fewer swelling attacks each month than the people who took placebo. At the beginning of the study, people had about 3 attacks per month, on average. After 6 months, there were:
- 1.31 attacks per month on average in people taking Orladeyo 150 milligrams
- 1.65 attacks per month on average in people taking Orladeyo 110 milligrams
- 2.35 attacks per month on average in people taking placebo
Reduced rate of attacks. The study also looked at how many people had at least a 50% reduction in the number of attacks during the study. In other words, they counted how many people had half as many attacks (or less) while they were in the study compared to before the study started. More people who took Orladeyo had at least a 50% reduction in attacks during the study.
Your results may differ from what was seen in clinical studies.
How Quickly Will Orladeyo Work for HAE?
If Orladeyo is working for you, it can start to lower your risk of a swelling attack within the first week. Over time, you should notice that you are having fewer attacks overall and that they are happening less often. In the clinical trial, the number of attacks began to decrease during the first month of taking the medicine.
Do not change your dose of Orladeyo without talking to your health care provider first, regardless of whether it seems to be working for you. Higher doses of Orladeyo can have serious side effects. If you are concerned that the medicine is not working or is causing too many side effects, your health care provider can discuss your treatment options with you.
What If I Stop Taking It?
Orladeyo must be taken every day in order to continue to prevent swelling attacks. If you stop taking it each day, your risk of a swelling attack will go up again. The medicine will begin to wear off quickly after stopping it. If you are considering stopping your Orladeyo, speak with your health care provider first. They can discuss your other treatment options with you.
How Can I Prevent or Manage Side Effects?
Orladeyo can cause gastrointestinal (GI) side effects such as stomach pain, nausea, vomiting, diarrhea, and acid reflux. For many people, these side effects are worse right after starting the medicine. They often get better within a few days and, in most cases, go away completely within the first month. One way to help reduce GI side effects is to make sure that you always take your dose of Orladeyo with food. If you are still having GI side effects after a few weeks of taking the medicine, talk with your health care provider. They may discuss lowering your daily dose or considering other treatment options.
These are not all of the possible side effects. Talk with your health care provider if you are having symptoms that bother you. If you experience anything that you think may be caused by Orladeyo, you can also report side effects to the FDA at 800-FDA-1088 (800-332-1088).
Are There Any Interactions With Other Medicines?
It is important that you tell your pharmacist or other health care provider about all of 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 to decide the best treatment plan for you.
Orladeyo can alter the blood levels of other medicines, and other medicines can alter the blood levels of Orladeyo. In some cases, your health care provider may need to change the dose of some of your other medicines. They may also need to prescribe a lower dose of Orladeyo.
Make sure that you let your health care provider know if you are using a hormonal birth control medicine that contains desogestrel. Some examples of these medicines include Apri, Freya, Linessa, and Mirvala. Orladeyo may increase the blood levels of these medicines.
Are There Any Special Steps Required to Get Orladeyo?
Orladeyo is available through a program called Empower Patient Services. This group will work with you to address any prior authorization requirements from your insurance company. They may also be able to provide you with a coupon from the drugmaker that will allow you to pay as little as $0 for your prescription. The group will also coordinate with a specific pharmacy, which will ship your Orladeyo prescription to you. You can find out more at orladeyo.com/empower-patient-services.
