Navigating Anemia: What to Know About Aqvesme for Thalassemia

Written by Jessica Elste, BCPS, PharmD
Medically Reviewed by Patricia Weiser, PharmD on February 22, 2026

Your blood carries oxygen to all of the cells in your body. When there are problems with red blood cells, you may feel weak and tired and may have to take medicines or receive blood transfusions to manage this.

Aqvesme (mitapivat) was approved in 2025 as the first pyruvate kinase activator taken by mouth to treat adults with anemia (low red blood cells) caused by certain blood disorders called alpha- or beta-thalassemia.

Thalassemia is a rare inherited (passed down in families) blood disease that affects your body’s ability to make hemoglobin. Hemoglobin is a protein in your red blood cells that helps carry oxygen throughout your body. When you lack enough hemoglobin, your red blood cells do not work properly and are destroyed. When there are fewer red blood cells in your body to carry oxygen, you may experience symptoms of anemia, such as tiredness, weakness, and difficulty breathing.

Aqvesme is a medicine that helps red blood cells make and use energy more effectively. It works by turning on an important enzyme (a helper protein) inside red blood cells called pyruvate kinase. When this enzyme works better, red blood cells have more energy to stay healthy and function normally.

In people with alpha- or beta-thalassemia, red blood cells are made with an imbalance in their building blocks. This causes stress and damage inside the cells, so many of them do not develop properly or break down earlier than they normally would.

By boosting pyruvate kinase activity, Aqvesme helps red blood cells work better and last longer. It also reduces the early destruction of red blood cells. These effects may help improve symptoms of anemia in people with thalassemia.

Aqvesme can cause serious liver damage. Because of this risk, the medicine is only available through a special program called the Aqvesme REMS program. Before you receive your prescription for Aqvesme, you, your health care provider, and your pharmacy will all need to be registered through the Aqvesme REMS program. This program makes sure that everyone knows about the risk of liver damage, symptoms to look for, and that you receive proper monitoring for liver damage during your treatment with Aqvesme. Your health care provider will check liver function tests at different times throughout your treatment.

  • Before starting treatment. Your health care provider will order liver function tests, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and total bilirubin, before you get your first dose of Aqvesme. This will help make sure that your liver is healthy. This will also give a point of reference to compare future tests with to make sure your liver stays healthy enough to continue treatment. 
  • After your first dose. Your liver function tests will be checked again after your first dose, then every four weeks for at least six months. After that, your health care provider will continue to check your liver function as needed.

Tell your health care provider right away if you experience any symptoms of liver damage, such as nausea, loss of appetite, jaundice (yellowish eyes and skin), or stomach pain or swelling. Your health care provider may have you stop taking Aqvesme if you experience symptoms of liver damage or if your labs show signs of liver damage during treatment. If this happens, you will work with your health care provider to decide whether and when it is safe to restart Aqvesme.

To study the safety and effectiveness of Aqvesme for the treatment of anemia in people with alpha- or beta-thalassemias, researchers conducted a clinical trial called ENERGIZE. To be able to participate in the trial, people had to have alpha- or beta-thalassemia, a low hemoglobin concentration indicating anemia, and not be dependent on blood transfusions. This means that they could not have received more than 5 units of red blood cells transfused within six months or have had any red blood cell transfusions within eight weeks before the study started. People in the study were either given Aqvesme or a placebo containing no medicine by mouth twice a day for six months.

People in the ENERGIZE trial had the following characteristics at the beginning of the study:

  • The median (middle) age was 41 years.
  • 63% were women, and the rest were men.
  • 56.2% were White, 39.2% were Asian, 1% were Black or African American, 0.5% identified as multiracial, and 2.1% had unknown race.
  • The median hemoglobin level before starting the study was about 8.4 grams per deciliter (g/dL).
  • About 86% had not received a red blood cell transfusion.
  • About two-thirds of people had beta-thalassemia, and the rest had alpha-thalassemia.

A second study, called ENERGIZE-T, was done to evaluate the safety and effectiveness of Aqvesme in adults with alpha- or beta-thalassemia who were classified as transfusion-dependent. To be considered transfusion-dependent, a person must have received 6-20 units of red blood cells in the 24 weeks before the study started and could not have gone more than six weeks without a transfusion during that time. People in the ENERGIZE-T study were either given Aqvesme or a placebo by mouth twice daily for 48 weeks. 

People in the ENERGIZE-T trial had the following characteristics at the beginning of the study:

  • The median age was 33.5 years.
  • 53% were women, and the rest were men.
  • 60.1% were White, 30.2% were Asian, 0.8% were Black or African American, 0.8% identified as multiracial, 3.9% had unknown race, and race was not reported for the rest.
  • The median hemoglobin level before starting the study was 8.9 g/dL.
  • 71% had received transfusions of more than 12 units of red blood cells.
  • 44% of people had beta-thalassemia, and the rest had alpha-thalassemia.

In the ENERGIZE study, effectiveness was measured by how many people’s hemoglobin “responded” to treatment with Aqvesme or placebo. They defined a response as an increase in the hemoglobin by at least 1 point when the level was averaged over the last three months of the study. So if a person’s hemoglobin was 9 g/dL at the start of the study, they would be classified as having a hemoglobin response if their average hemoglobin went up to at least 10 g/dL over the last three months of treatment. 

  • About 42% of people treated with Aqvesme had a hemoglobin response compared to about 2% of people treated with a placebo.
  • More people treated with Aqvesme also reported improvements in tiredness, compared with people who received a placebo. Tiredness can be a sign of more severe anemia.

In the ENERGIZE-T study, effectiveness was measured by how much the treatment lowered the need for blood transfusions. A person was considered to have “responded” to treatment if they needed at least 50% fewer blood transfusions and at least two fewer units of red blood cells during any 12-week period within the first 48 weeks of treatment, compared with before starting the medicine. The researchers called this a transfusion reduction response.

  • About 30% of people treated with Aqvesme had a transfusion reduction response compared to about 13% of people treated with a placebo.

Your results may differ from what was seen in clinical studies.

In the ENERGIZE study, people treated with Aqvesme started to see improvements in their hemoglobin levels and reduced feelings of tiredness within four weeks of starting the medicine.

Your results may differ from what was seen in clinical studies.

The most common side effects of Aqvesme are headache and trouble sleeping (insomnia).

In studies, about 25% of people reported headache as a side effect while taking Aqvesme. Tips to help get rid of headaches include:

  • Drink plenty of liquids. 
  • Lie down in a quiet place with the lights dimmed. 
  • Use a cold compress on your head for 15 minutes, or try a warm cloth on the back of your head to ease tension.
  • Try an over-the-counter (OTC) pain reliever. Your health care provider or pharmacist can help you choose a product that is safe for you.

Nearly 1 in 4 people had insomnia while taking Aqvesme in studies. People reported having trouble falling asleep, waking up in the middle of the night, and/or waking up too early. Tips to help you sleep better include:

  • Avoid caffeine later in the day. This includes drinks and foods that contain caffeine, such as chocolate.
  • Go to bed and wake up at the same time each day. This helps your body stay on a healthy sleep schedule so you can fall asleep faster and sleep better through the night.
  • Ask your health care provider if a sleep aid or melatonin is safe for you.

This is not a complete list of side effects. Tell your health care provider if these or other side effects bother you or do not go away.

Many medicines can interact with Aqvesme. Tell your health care provider about all medicines and supplements you take or have recently stopped. Some common drug interactions with Aqvesme are further described below. 

CYP3A inhibitors. CYP3A enzymes process and remove some medicines from the body, including Aqvesme. Taking certain medicines that inhibit (decrease the activity of) this enzyme can increase the risk of side effects from Aqvesme. Aqvesme should not be taken with any medicines that moderately or strongly inhibit CYP3A.

CYP3A inducers. Taking certain medicines that induce (increase the activity of) the CYP enzyme can cause Aqvesme to not work as well. Aqvesme should not be taken with any medicines that strongly induce CYP3A. If you need to take Aqvesme with a medicine that moderately induces CYP3A, you may need extra monitoring to make sure Aqvesme is working.

Substrates of UGT1A1 or certain CYP enzymes. Some medicines may be substrates of certain CYP enzymes or another enzyme called UGT1A1. This means they are broken down in the body by those enzymes. Aqvesme induces UGT1A1 and several different CYP enzymes, causing them to remove those other medicines from your body more effectively. This can cause the other medicines not to work as well.

P-gp substrates. Aqvesme inhibits (blocks) the activity of another enzyme called P-gp. If you take Aqvesme with other medicines that are broken down by P-gp in your body, it can increase your risk of side effects from those other medicines.

This is not a complete list of interactions. Tell your pharmacist or other health care provider about all the prescription or OTC medicines, vitamins/minerals, herbal products, or other supplements you take or have recently taken. This will help them know if there are any interactions with Aqvesme.

 

 

 

The drugmaker offers a patient support program that will help you get started with treatment and may be able to help make Aqvesme more affordable for you. To find out more, you can call 877-772-4467.

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