If you have systemic mastocytosis, your health care provider may recommend a medicine to treat it. One such medicine is Ayvakit (avapritinib), an oral tablet.
Systemic mastocytosis is a rare condition where too many mast cells build up in your body. Mast cells are a type of white blood cell that can release histamine, which can cause itching and inflammation. “Systemic” means the symptoms can affect your whole body. Systemic mastocytosis especially affects your skin, tissues, and organs. There are different types of systemic mastocytosis, ranging from slow-growing to advanced forms that are aggressive and cancerous.
The FDA approved Ayvakit in 2020. It belongs to a class of medicines called kinase inhibitors. Ayvakit works by blocking certain proteins that help mast cells grow. This medicine is also commonly used to treat gastrointestinal stromal tumor (GIST), a rare type of cancer that affects the esophagus, stomach, and intestines. Ayvakit may also be used for other conditions as determined by your health care provider. This article focuses on the use of Ayvakit for systemic mastocytosis.
Is Ayvakit Right for My Systemic Mastocytosis?
Your health care provider will do a series of tests to check which type of systemic mastocytosis you have. The test results, along with any symptoms you are experiencing, can help your health care provider determine if Ayvakit is right for you. Ayvakit is FDA-approved to treat the following types of systemic mastocytosis in adults:
Advanced systemic mastocytosis (AdvSM), including three specific subtypes, as follows.
- Aggressive systemic mastocytosis, where the buildup of mast cells causes an organ to stop working as well as it should. Commonly affected organs include the liver, digestive tract, bone, or bone marrow.
- Systemic mastocytosis with an associated blood disorder (hematological neoplasm), which occurs when mast cells build up at the same time as another blood disorder, such as myelodysplastic syndromes.
- Mast cell leukemia, a rare and fast-growing cancer where a buildup of mast cells takes up at least 20% of your tissues or organs.
Indolent systemic mastocytosis (ISM), which is a benign (meaning not cancerous) condition that is milder than other forms of systemic mastocytosis. Mast cells usually build up slower and lower, which may cause uncomfortable symptoms but does not typically lead to organ failure.
Taking Ayvakit may not be safe if your platelet count is too low. Platelets are a type of blood cell that help you stop bleeding. Your health care provider will monitor your platelet counts before and during Ayvakit treatment to make sure your platelets are within a healthy range. This helps to reduce the risk of brain bleeding, which can be a serious side effect.
How Does Ayvakit Work for Systemic Mastocytosis?
Kinases are enzyme proteins that help send and receive signals within the body. Ayvakit belongs to a class of medicines called kinase inhibitors, which are designed to block certain signals that help cells grow.
More specifically, Ayvakit works for systemic mastocytosis by blocking a protein called KIT, which has a specific change (mutation) in many people with systemic mastocytosis. This mutation makes the KIT protein overactive, causing too many mast cells to grow and build up in the body. This can lead to inflammation and damage, and the resulting symptoms can vary depending on the tissues and organs affected.
By targeting kinases including the mutated KIT protein, Ayvakit helps slow down or stop the excessive buildup of mast cells. This can help reduce symptoms and damage in people with systemic mastocytosis.
How Do I Take Ayvakit?
Ayvakit comes as a tablet that you swallow. Take Ayvakit on an empty stomach, either at least one hour before or two hours after a meal. This timing helps your body absorb the medicine better.
The typical dosage of Ayvakit is as follows:
- For advanced systemic mastocytosis (AdvSM), the typical dosage of Ayvakit is 200 milligrams once daily.
- For indolent systemic mastocytosis (ISM), the usual dosage of Ayvaki is 25 milligrams once daily.
Ayvakit is usually a long-term treatment. You will likely continue taking it as long as it is working safely for you. If you experience certain side effects, your health care provider may need to adjust your dose, temporarily stop the medicine, or in some cases, stop treatment completely.
Always follow your provider’s instructions and let them know about any side effects you experience, especially if they do not go away. Seek medical care right away for any side effects that seem severe.
How Was Ayvakit Studied for Systemic Mastocytosis?
Three clinical trials were done to test how well Ayvakit works for systemic mastocytosis. These trials also looked at the safety of Ayvakit by collecting information about side effects.
The EXPLORER and PATHFINDER trials studied how well Ayvakit worked for treating advanced systemic mastocytosis (AdvSM). Both trials were open-label, meaning everyone knew they were taking Ayvakit. Here are some details about the participants and how the studies were conducted.
- These trials included adults ranging from 37 to 85 years. More than half (58%) were male, and most participants were White (98%). The race of the other people in the trail was not noted.
- Everyone had a subtype of AdvSM: aggressive systemic mastocytosis, systemic mastocytosis with an associated blood disorder (hematological neoplasm), or mast cell leukemia.
- Most people had a good performance status when the study began, meaning they were able to do daily activities. Many were receiving other medicines, such as steroids, for AdvSM symptoms and about half had tried a medicine called midostaurin (Rydapt) in the past.
- People in these trials took Ayvakit once daily for up to 24 weeks.
The main goal was to measure how many people with AdvSM responded to Ayvakit, based on specific criteria related to how their condition improved or worsened. To measure this, the participants had regular exams and tests to track their progress.
Another study, the PIONEER trial, looked at how well Ayvakit worked for indolent systemic mastocytosis (ISM) by comparing its effects to a placebo (a pill that contains no medicine). Here are some details about how the study was done and who participated.
- The trial included 212 adults ranging from age 18 to 77, with half being 50 or older. Most (71%) were female, and 77% were White. Less than 1% were Asian, 3% were of another race, and 19% did not report their race. In terms of ethnicity, 4% identified as Hispanic or Latino.
- Everyone had ISM with moderate to severe symptoms when they joined the study, despite using multiple medicines for symptom relief.
- People in this study were randomly assigned to take either Ayvakit or a placebo for up to 24 weeks. Everyone also received supportive care, such as medicines for symptom relief. No one knew if the pill they were given was Ayvakit or a placebo.
The main goal of this study was to see how well Ayvakit worked for treating ISM. Participants provided daily ratings of their symptoms (such as itching, pain, stomach issues, and fatigue) using a rating scale where higher scores indicated worse symptoms. To measure Ayvakit’s effectiveness, the researchers compared the average change in these symptom scores from the start to the end of the study.
What Are the Main Benefits of Ayvakit for Systemic Mastocytosis?
The trials evaluating Ayvakit for advanced systemic mastocytosis (AdvSM) found that more than half of people had improvement while taking Ayvakit. Improvement was defined as having a treatment response, which means their symptoms were reduced and at least one of their organs had a full or partial recovery from damage. Here are some of the main results of the EXPLORER and PATHFINDER trials.
- Out of the 53 people with AdvSM treated who took Ayvakit, 57% experienced a treatment response.
- About 19% of participants experienced stable disease, meaning their condition did not improve but it also did not get worse.
- Of those that improved, half had a response that lasted at least 38.3 months.
- Half of the people started experiencing a response treatment in less than 2.1 months, while the other half took longer to respond.
The trial evaluating Ayvakit for indolent systemic mastocytosis (ISM) also had positive results, finding that people had a reduction in their overall symptoms while taking Ayvakit. This means, on average, their symptoms became less bothersome than they were before the study began. Here are some of the main results of the PIONEER trial.
- People who took Ayvakit had a decrease in their total symptom scores, with an average reduction of 15.33 points. This means their symptoms were reduced more than those taking the placebo, who had a smaller reduction of 9.64 points.
- About 25% of people who took Ayvakit had their symptoms decrease by 50% or more. In comparison, only 10% of people taking the placebo experienced this result.
Together, these studies support Ayvakit as an effective treatment option for systemic mastocytosis. Note that Ayvakit is not meant to cure this condition, and your results may be different from what was seen in studies.
What Is Its Place in Therapy?
According to treatment guidelines, Ayvakit is one of the first-line treatment options for people with advanced systemic mastocytosis (AdvSM). “First-line” refers to an initial medicine given to someone who has not yet received treatment for a particular condition. Ayvakit and other first-line medicines have been shown to effectively manage symptoms and slow the worsening or progression of the disease.
In addition, Ayvakit is the first medicine specifically approved by the FDA to treat indolent systemic mastocytosis (ISM). Studies show that Ayvakit can help reduce the mast cell burden and may improve quality of life by treating the underlying cause of the disease.
Ayvakit is not recommended for people with very low platelet counts due to the risk of serious side effects. A health care provider can help determine if Ayvakit is right for you.
What Types of Drug Interactions Can Happen With Ayvakit?
Ayvakit can interact with certain medicines, particularly those that affect enzymes in the liver called CYP3A, which help your body process many medicines. Some medicines can increase or decrease the levels of Ayvakit in your body, possibly affecting how well it works or increasing side effects.
Always tell your health care provider about any prescription, over-the-counter (OTC) medicines, vitamins, herbal products, or supplements you are using. They can check for possible interactions and advise how to avoid or manage them. For instance, they may recommend changes in your other medicines to help avoid interactions. In some cases, your health care provider may reduce your dosage of Ayvakit to help prevent increasing side effects. Do not change any of your medicines or dosages without first discussing it with your prescriber.
Also, while not a direct interaction, blood thinner medicines may raise the risk of brain bleeding, which is a rare but serious side effect of Ayvakit. An example of a blood thinner is warfarin (Coumadin, Jantoven). Your health care provider may monitor you closely if you are taking a blood thinner or have other factors that could raise the risk of side effects with Ayvakit.
How Can I Get Ayvakit?
Ayvakit requires a prescription from a health care provider. This is usually a hematologist (blood disorder specialist), oncologist (cancer specialist), or other health care provider who specializes in treating your condition.
Ayvakit is a specialty medicine. Your local pharmacy does not carry it. Instead, your health care provider will send your prescription to a specialty pharmacy. They can ship the medicine to your home or doctor’s office.
Is There Any Cost Assistance Available?
A cost assistance program is available from Blueprint Medicines, the manufacturer of Ayvakit. It may reduce the amount you pay. Whether you qualify to enroll may depend on what type of insurance plan you have or if you are uninsured. To learn more about Ayvakit costs and copay savings, visit the following websites for more information.
- Visit this website if you or a loved one has AdvSM: www.ayvakit.com/advanced-systemic-mastocytosis/
- Visit this website if you or a loved one has ISM: www.ayvakit.com/indolent-systemic-mastocytosis/paying-for-ayvakit/
You can also call 888-258-7768 to connect with a representative for financial support information and other resources.
