PIK3CA-related overgrowth spectrum (PROS) is a group of rare conditions that cause areas of the body to grow too much or in an unusual way. People are born with PROS due to mutations (mistakes) in a gene called PIK3CA. This means that the gene is not working correctly and allows the body to change the way it grows.
Vijoice is the first FDA-approved drug to specifically target the causes of PROS. The active ingredient in Vijoice (alpelisib) was originally approved and is currently used for the treatment of certain breast cancers. Vijoice was first made available for people with PROS as part of an extended access program (EAP), which allows people to use a medicine if they have a severe, life-threatening condition.
How the Medicine Works
The PIK3CA gene helps to guide the PIK3CA protein to make sure that cells in your body grow, divide, and die normally. When there is a mutation in PIK3CA, the PIK3CA protein starts to work too fast and too much. This causes the body to have overgrowth of specific body parts, like skin, blood vessels, bones, or the brain. These gene and protein changes are also seen as an overgrowth of cancer cells.
PROS can affect some but not all parts of the body. The signs and symptoms can be different from person to person. Examples of the conditions linked to PROS are listed in the table below.
| PROS Condition | Areas Commonly Affected |
| CLOVES Syndrome | |
| Klippel-Trenaunay Syndrome (KTS) |
|
| Isolated Lymphatic Malformation (ILM) |
|
| Megalencephaly-Capillary Malformation Syndrome (MCAP) |
|
| Hemimegalencephaly (HME) |
|
| Hemihyperplasia-multiple Lipomatosis (HHML) |
|
| Macrodactyly |
|
| Facial Infiltrating Lipomatosis (FIL) |
|
| Fibroadipose Hyperplasia or Overgrowth (FAO) |
|
There is not a cure for PROS, so treatment depends on the symptoms and tissues involved. Treatments include medicines for symptoms like painful or itchy skin or seizures; antibiotics; or growth hormones. Also, surgery or other therapies can be helpful for certain overgrowths or spine issues. But these procedures come with their own risk, and regrowth is common after surgery.
Since the PIK3 pathway is also overactive in certain cancers, some cancer treatments have been used with PROS patients. Vijoice contains the ingredient alpelisib that is used along with other medicines to treat certain breast cancers. Vijoice works by blocking activity in the PIK3 pathway. This helps to slow down the overgrowth of tissues, reduce the size of existing areas, and reduce some symptoms. Vijoice was the first medicine approved for PROS conditions.
How Should I Take This Medicine?
Vijoice is taken with food at the same time each day. Depending on your dose and ability to swallow tablets, your health care provider may prescribe Vijoice tablets or granules. You should not take tablets and granules together.
If you are not able to swallow the tablets, two options are described in the table below. Talk to your pharmacist or other health care provider about the best choice for you.
| Vijoice tablet suspension |
|
| Vijoice granules | Hold the top of the package (with the cut line on top) and shake to get all the granules to the bottom. Cut along the cut line using scissors. The granules can be taken two ways:
|
What Studies Were Completed?
Two studies (EPIK-P1 and EPIK-P3) have been done to see if Vijoice was safe and effective for PROS conditions.
EPIK-P1 was a study designed to look at the past use of a Vijoice in adults and children with a diagnosis of severe or life-threatening PROS. In this study, the medical charts were reviewed of each person who took at least one dose of Vijoice. In this study:
- There were 57 people (39 children and 18 adults), with an average age of 14 years.
- More than half of the people were female (57%).
- The races of 89% of the people in this study were not reported, and the remaining 11% were White.
EPIK-P3 is an ongoing study that includes looking back at the medical charts of people who were included in EPIK-P1 and had taken Vijoice for at least two years and up to six years. In this study:
- There are 34 children and 14 adults from the end of the EPIK-P1 assessment.
- EPIK-P3 is ongoing, and the full results have not been published.
- A final racial breakdown of those in this study was not available.
Average overall treatment for the two studies was 42 months, with 22.8% of people treated for more than 60 months. Over 80% of people in the studies had at least one surgery before starting Vijoice.
In EPIK-P1, the efficacy results included 37 people with at least one lesion and imaging of the lesion. Efficacy was defined as response to treatments at 24 weeks, based on reducing a lesion by at least 20%. The study also looked at how long people responded to Vijoice, changes in symptoms, changes in physical performance, PROS-related surgeries, and occurrence of side effects.
EPIK-P3 looked at the safety of Vijoice and how people responded to treatment. Efficacy outcomes included overall assessment of symptoms, other treatments required, and PROS-related surgeries.
What Benefits Were Seen in the Studies?
In EPIK-P1, 27% of the people who took Vijoice responded. For the people with a response, 70% had a response for at least six months and 60% had a response for at least 12 months. This means that the volume of their targeted lesions decreased.
- 30.4% of children taking Vijoice had a response, where 68% had a reduction in at least one target lesion
- 55.6% of adults taking Vijoice had a response, where 88.8% had a reduction in at least one target lesion
Common symptoms. The commonly reported symptoms were tracked and combined between EPIK-P1 and EPIK-P3. Improvements were noted based on the percentage of people who reported less severe symptoms or relief from the following symptoms.
Symptom | Percent Improvement |
| Fatigue | 100% |
| Vascular malformations | 92.1% |
| Disseminated intravascular coagulation (DIC), a blood clotting disorder | 86.2% |
| Difference in the size (asymmetry) of limbs | 86.2% |
| Pain | 87% |
Surgeries. For most people taking Vijoice, the number of surgeries were reduced. About 70% of children and 90% of adults did not require surgery. Some of the surgeries that did happen were done due to disease improvement.
Functional improvements. Some of the people in both studies had functional assessments completed. Those people completed assessments that looked at their daily activity, physical ability, and ability to care for themselves. The combined results from the studies showed that 81% (38 out of 47 people) had improvements in the last assessment they took during the study. This means that most of the people who had taken Vijoice felt better and were more able to do everyday tasks, compared with their abilities before taking Vijoice.
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 the Medicine Is Working
Vijoice works gradually, so you may not see quick changes in your symptoms. The long-term goal is to slow progression, so it is important to track your symptoms and review with your health care provider. You may see these improvements:
- Decreased size of the overgrowth of tissues like fat (lipomas), blood vessels (vascular malformations), or body parts
- Improved appearance and function of affected areas
- Slowed progression of symptoms
- Fewer associated symptoms, like seizures or itchy skin
Always continue your medicine even if you don’t feel changes in your symptoms right away.
How Can I Prevent and Manage Side Effects?
The most common side effects are diarrhea, dehydration, mouth sores (stomatitis), increased blood sugar (hyperglycemia), or thinning hair (alopecia). In the studies, most of these side effects were mild to moderate.
Diarrhea. If you have diarrhea while taking Vijoice, stay well-hydrated by drinking plenty of water, sports drinks, or clear broth, and try small, frequent meals. You will be told how to take the medicine to lessen the effect of diarrhea. Call your health care provider right away if you get diarrhea or if you have more than two bowel movements in one day. If you are given medicine to prevent or treat diarrhea, take it exactly as your health care provider tells you. Call your health care provider right away if you have:
- Severe diarrhea
- Stomach (abdominal) pain
- Diarrhea that does not go away
- Diarrhea with weakness, dizziness, or fever
- Mucus or blood in your stool
Dehydration. Vijoice may cause dehydration, especially if you have diarrhea during treatment. Dehydration may lead to low blood pressure, especially when you stand up (orthostatic hypotension), or kidney damage. Call your health care provider right away if you have any of the following symptoms of dehydration, low blood pressure, or kidney damage:
- Dizziness or lightheadedness
- Weakness or unusual tiredness
- Confusion
- Unsteadiness
- Peeing less than normal
- Swelling in your legs, ankles, and feet
- Loss of appetite or nausea
- Difficulty catching your breath, or chest pain or pressure
- Seizures
- Extreme thirst
Mouth sores. Vijoice may cause mouth sores, which can cause inflammation, irritation, and pain. If you have mouth sores, you can try rinsing your mouth with salt water a few times a day or putting ice chips or a cold compress on the sores. Try to avoid mouthwashes that contain alcohol and spicy, acidic, or rough foods. Talk to your health care provider about over-the-counter (OTC) treatments.
Increased blood sugar. Your health care provider may monitor your blood sugar before starting Vijoice and during your treatment. If you have a history of diabetes, you may need to monitor your blood sugar more closely. Contact your health care provider right away if you have any of the following symptoms of increased blood sugar or if you have high blood sugar at home:
- Thirsty more than usual
- Peeing more than usual
- Dry mouth
- Increase in hunger
- Tiredness
- Feeling sick to your stomach
- Feeling tired, woozy, or confused
- Your breath smelling fruity
- Trouble breathing
- Dry or flushed skin
Thinning hair. Vijoice can cause your hair to be thinner during treatment. Use gentle hair products and avoid excessive heat styling. Talk to your health care provider about products or vitamin supplements that may help with hair health.
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?
Due to the risk of side effects, your health care provider may do the following tests before and during your treatment:
Pregnancy. Vijoice can harm an unborn baby. Your health care provider may do a pregnancy test before starting Vijoice to confirm the absence of a pregnancy. Tell your health care provider if you are pregnant or plan to become pregnant before starting Vijoice.
Blood sugar. Vijoice may increase your blood sugar. Your health care provider may do a blood test to check your blood sugar levels before starting Vijoice and may monitor it during treatment. If you have a history of diabetes, your health care provider may monitor your blood sugar more closely.
What Types of Interactions Can Happen?
Several medicines can interact with Vijoice. Before taking Vijoice, tell your health care provider about any prescription or over-the-counter (OTC) medicines, vitamins/minerals, herbal products, and other supplements you are using.
Blood levels of Vijoice. Several medicines can change the blood levels of Vijoice. This may make Vijoice less effective. These changes are related to the effect of these medicines on enzymes called CYP or proteins called BCRP. Let your health care provider know if you are using any of the following medicines or foods that change these enzymes. These medicines should not be used at the same time as Vijoice:
- Strong inducers of CYP3A4 enzymes, which include apalutamide (Erleada), carbamazepine (Epitol, Equetro, Tegretol), enzalutamide (Xtandi), ivosidenib (Tibsovo), lumacaftor/ivacaftor (Orkambi), mitotane (Lysodren), phenytoin (Dilantin), rifampin (Rifadin, Rifampicin, Rimactane), and St. John’s wort
- BCRP inhibitors, which include avanafil (Spedra, Stendra), cyclosporine, eltrombopag (Promacta), febuxostat (Uloric), gefitinib (Iressa), imatinib (Glivec), nilotinib (Tasigna), and omeprazole (Prilosec)
Blood levels of other medicines. Vijoice can affect the blood levels of some medicines. These changes are related to the effect on these medicines by an enzyme called CYP2C9. This may make these medicines less effective. Ask your health care provider about the medicines you are taking. They may closely monitor any affected medicine while you are taking Vijoice.
This is not a complete list of medicines that may interact with Vijoice. 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 to change your dose.
Getting Your Medicine: What to Expect
Insurance approval. Your insurance may require approval for using this medicine, also called prior authorization. The insurance company reviews the prescription from your health care provider to make sure it is covered and determines the process that needs to be followed.
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://us.vijoice.com/pik3ca-related-overgrowth-spectrum-pros/patient-support/financial-support or by calling 877-577-7756.