Lyfgenia for Sickle Cell Disease

Written by Chelsey McIntyre, PharmD
Medically Reviewed by Laurel Riemann, PharmD on October 27, 2025
9 min read

If you or someone you know has sickle cell disease (SCD), you may have heard of Lyfgenia, one of two gene therapies approved for this condition. Gene therapies are the only treatments for SCD that can actually help your body make its own healthy hemoglobin. 

People with SCD make an abnormal form of hemoglobin, the protein in your red blood cells that carries oxygen through your body. This protein is usually flexible and can fit through your smallest blood vessels without any issue. But people with SCD have rigid hemoglobin that can get stuck and block the flow of blood through smaller blood vessels. This rigid hemoglobin is shaped like a sickle (a crescent) and is known as hemoglobin S. Normal hemoglobin is known as hemoglobin A.

Sickle cell disease (SCD) is an inherited condition that is passed down from parents to their children. It is caused by a specific change (mutation) in a gene that has the directions to make hemoglobin. But not everyone with this mutation has SCD. Having one copy of this mutation from one parent and a normal gene from the other parent is known as sickle cell trait. People with sickle cell trait usually make enough normal hemoglobin, so they usually do not have any symptoms. 

If you have SCD, you are not able to make any normal hemoglobin. You may have inherited two copies of the sickle cell trait, or you may have inherited one copy of the sickle cell trait plus one copy with a different mutation that results in abnormal hemoglobin.

There are three main types of SCD:

  • HbSS (sickle cell anemia): This is the more serious form of the condition. In HbSS, a person has inherited the sickle cell trait from both parents, meaning that the genes from both parents are telling their body to make hemoglobin S.
  • HbSC: This form of SCD may not be as severe as HbSS. In HbSC, a person has inherited the sickle cell trait from one parent and a different type of abnormal hemoglobin, called hemoglobin C, from the other parent.
  • HbS beta-thalassemia: A person with HbS beta-thalassemia has inherited the sickle cell trait from one parent and the beta-thalassemia gene from another parent. Beta-thalassemia is a different genetic disorder that changes the shape of hemoglobin. Some forms of HbS beta-thalassemia are very serious, while others are milder.

In SCD, red blood cells get trapped in blood vessels, limiting or blocking the flow of blood to parts of the body. Most people with SCD begin to have symptoms during infancy. These symptoms may be different for each person and will change with age and time. However, most people with a serious form of this condition will have the following significant health problems:

  • Vaso-occlusive crises (VOC, or pain crises): VOCs occur when blood flow to a part of the body is completely blocked. The pain during these crises can be all-consuming and may be sharp, stabbing, or throbbing. These crises may be brought on by illness or stress, but the causes of most VOCs are often unclear. A VOC in the lungs can be life-threatening and is known as acute chest syndrome.
  • Blood clots: Hemoglobin S changes the way your blood flows, increasing the risk of blood clots. Blood clots in the lungs can be serious and life-threatening. Blood clots in the brain can cause a stroke, which can be life-threatening and also cause long-term problems.
  • Joint problems: Blockage of blood flow to the bones or joints can cause joint damage and long-term problems. Many people with SCD have chronic pain in their shoulders, knees, hips, and ankles, which can cause trouble with walking and movement.

Many people will also have other symptoms in different parts of their bodies that can significantly reduce their quality of life.

In the past, treatments for SCD have focused on reducing the buildup of hemoglobin S in the blood. Some examples of these treatments include crizanlizumab, hydroxyurea, and L-glutamine. Many people also receive regular blood transfusions.

In 2023, the FDA approved two novel treatments for SCD, called gene therapies. Lyfgenia (lovotibeglogene autotemcel) is one of those gene therapies. It works by adding a new gene to your body that helps you form hemoglobin A, which is the normal, flexible form of hemoglobin. Once you have received a complete course of treatment with Lyfgenia, this new gene becomes a permanent part of your body. Having healthy hemoglobin A can help reduce or stop VOCs and other problems in people with SCD.

Lyfgenia is a personalized gene therapy that is given by a health care provider in a hospital. The actual process of receiving Lyfgenia involves multiple steps and procedures that may take up to six months to complete.

First, your health care provider must collect your stem cells and send them to a lab. In order to have your stem cells collected, you may need to stop taking certain medicines and start taking other medicines. You may also need to receive a blood transfusion. Once your cells are collected, it may take up to four months for the lab to prepare your modified (edited) cells.

When your modified cells are ready, you will need to receive “conditioning” treatment that will clear all of the bone marrow cells from your body. The medicines used for conditioning have many side effects, and you may need to take other medicines to help prevent or treat these side effects. Since conditioning removes your body’s ability to fight off infections and increases your risk for bleeding, you will need to stay in the hospital during and after this treatment. 

Once your bone marrow is cleared, you will be ready to receive treatment with Lyfgenia, which is made of your own edited cells. These cells will be infused into your vein (IV) as a bone marrow transplant. Your body will use Lyfgenia to rebuild your bone marrow, a process called engraftment, which typically takes four to six weeks. Since you will still be at high risk for infection and bleeding as you wait for engraftment, you may need to remain in the hospital this entire time.

As your cells begin to engraft, your body will use the new gene found in your edited cells to make normal, flexible hemoglobin (hemoglobin A). Although you will still have some hemoglobin S in your body, the levels should be much lower. Most of your hemoglobin should be hemoglobin A. It can take four to six weeks for your body to fully respond to your bone marrow transplant with Lyfgenia.

Your health care providers will monitor the levels of blood cells in your body to determine when your bone marrow is functioning normally again. Once this happens, you should begin to notice a difference in your SCD symptoms. Most people have fewer VOCs after recovering from their treatment with Lyfgenia.

One small clinical study was done to see if Lyfgenia is safe and effective for the treatment of SCD. In total, there were 43 people in this study, all between the ages of 12 and 38. All of the people in this study had a diagnosis of severe SCD (HbSS).

Of the 43 people who started in the study, only 36 received conditioning treatment and treatment with Lyfgenia. Two people did not continue due to issues with the stem cell collection process, and five people dropped out for other reasons.

The study measured efficacy by seeing how many people did not have any VOCs for a full year. The “year” that was measured started six months after receiving Lyfgenia and continued until 18 months after receiving Lyfgenia. Of the 36 people, 32 had at least four severe VOCs or acute chest syndromes in the past two years and were followed for 18 months.

Of these 32 people, most (63%) were male, and almost everyone (97%) was Black/African American. The races of the two other people in this study were not provided.

Starting six months after treatment with Lyfgenia, the number of VOCs was counted.

  • No VOCs: 88% of people did not have any VOCs for the next year.
  • No severe VOCs: 94% of people did not have any severe VOCs for the next year.

What this means: During the full year that started six months after receiving treatment with Lyfgenia, most did not have any VOCs. This means that Lyfgenia reduced the number of VOCs by a large amount in most people in the study. These people had at least four severe VOCs or acute chest syndromes in the two years before the study started.

However, this study was small and only lasted for 18 months. It is not clear if Lyfgenia will work for everyone or if it will continue to work in the same way over time. Researchers are continuing to monitor the people who have received Lyfgenia so they can better understand its long-term effects.

In rare cases, the edited stem cells in Lyfgenia may not engraft. This is called engraftment failure. This did not happen during the clinical study of Lyfgenia, but it is a rare possibility for anyone who undergoes treatment. If this happens, your health care provider will infuse your original stem cells back into your body so they can engraft again. This means that your body will use your original stem cells, and you will not get any benefit from Lyfgenia.

In some cases, certain people may not be able to receive Lyfgenia because they have issues during the steps leading up to treatment. Some people may not have enough stem cells available for collection. Additionally, some people may have serious side effects from the conditioning medicines that clear all of the blood cells from your body.

Before you begin the process necessary to receive Lyfgenia, your health care provider will discuss the possible risks with you, as well as your options if any of these problems occur.

The conditioning medicine that is used to clear the bone marrow cells from your body will cause you to have severely low levels of white blood cells and platelets. This will increase your risk for infection and bleeding. To help prevent these problems, you will need to stay in the hospital until your bone marrow recovers. You may also need to take some medicines to reduce your risk for infections or bleeding and help manage other side effects.

Conditioning medicines may also make it difficult for you to get pregnant or get your partner pregnant. Before treatment, speak with your health care provider about your options if you may want to have children in the future.

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 have anything that you think may be caused by Lyfgenia, you can also report side effects to the FDA at 800-FDA-1088 (800-332-1088).

You may need to stop some of the medicines that you take for SCD before and during your treatment with Lyfgenia. After your treatment is complete, you may or may not need to restart these medicines.

Tell your health care provider about all of the medicines that you are currently taking for SCD and any other conditions. It is also important to tell them about any over-the-counter (OTC) medicines, vitamins/minerals, herbal products, or other supplements you take or have recently taken. Your health care provider will develop a treatment plan that is specific to you and your needs.

Treatment with Lyfgenia requires many different medical appointments and procedures in a complex process that can take up to six months. The drugmaker has a free support program that will connect you with a Patient Navigator who can provide you with more information about this process. If necessary, they may also be able to connect you with programs that offer financial assistance. You can find out more at www.mybluebirdsupport.com.