FDA Approves Zynteglo, the First Gene Therapy Medication for Beta-Thalassemia
Key takeaways:
In August 2022, the FDA approved Zynteglo (betibeglogene autotemcel) to treat severe beta-thalassemia, a genetic blood disorder, in kids and adults. It’s the first gene therapy medication for this condition.
Zynteglo helped about 89% of people avoid blood transfusions over a 12-month period in clinical trials. Some of the most common side effects were mouth sores, fever, and vomiting.
Zynteglo’s reported U.S. list price is $2.8 million, making it the most expensive medication in the country. Zyntelgo’s manufacturer is negotiating with insurance providers about what coverage options may look like.
Table of contents
In August 2022, the FDA approved Zynteglo (betibeglogene autotemcel) to treat severe beta-thalassemia in kids and adults. It’s the first gene therapy medication approved for this genetic blood disorder.
Before this approval, people living with severe beta-thalassemia didn’t have many treatment options to choose from. Blood transfusions are go-to sources of relief, but they can require frequent infusions — as often as every 2 to 4 weeks. They may also cause health problems over time, such as iron overload.
Zynteglo offers new hope for people living with beta-thalassemia. It’s a one-and-done medication that can help put an end to the need for blood transfusions. However, receiving it can be complicated for a number of reasons. For one, it’s expensive. You’ll also need to prepare for your infusion. Plus, it has side effects to keep in mind.
What is Zynteglo?
Zynteglo is a gene therapy medication that treats kids and adults living with transfusion-dependent (severe) beta-thalassemia.
If you have this type of thalassemia, your body has trouble making hemoglobin — a protein that carries oxygen in your red blood cells. This leads to a lack of red blood cells, and oxygen has trouble traveling around your body. Mutations in one or more hemoglobin genes cause this, so Zynteglo is designed to replace mutated cells with normal ones. It aims to fix the problem at its source.
When Zynteglo was put up for approval, the FDA made it a top item on its to-do list. It helped Zynteglo get through the approval process faster by giving it priority review, fast track, and breakthrough therapy designations. The agency also gave it orphan drug status (a designation given to medications that treat rare medical conditions). For comparison, most new medications are approved through a standard review process.
How does Zynteglo work?
Zynteglo is a type of cell-based gene therapy. Bone marrow stem cells are taken from your body, genetically modified, and placed back into your body as a form of treatment.
However, a few steps go into this. If your care team decides you’re eligible for Zynteglo, this is what the general process of receiving it looks like:
To start, you’ll receive a couple medications that boost your stem cell numbers. Once there’s enough of these cells, they’ll be collected from your body in a process called apheresis.
After enough of these cells are collected, they’ll be sent to a lab. If not enough are collected the first time around, you’ll receive more rounds of medication and apheresis until enough are gathered.
At a lab, your stem cells will be genetically modified to create your dose of Zynteglo. Then, the final product will be sent back to your treatment center.
Once your Zynteglo dose is ready to go, you’ll receive a chemotherapy medication like busulfan daily for a few days. This gets rid of any remaining stem cells in your body. Zynteglo will replace these cells with genetically modified ones. As a precaution, you may also receive medications to prevent side effects, such as seizures and liver problems.
After at least 2 days have passed since your last dose of busulfan, you should be ready to receive Zynteglo.
After your infusion, you’ll stay in a hospital for about 3 to 6 weeks for monitoring purposes.
How is Zynteglo dosed?
Zynteglo is infused into your vein once as a liquid medication. Depending on your dose, you’ll receive one to four bags of Zynteglo altogether. Each bag takes about 30 minutes to infuse. Your body weight helps determine your dose.
How effective is Zynteglo?
Getting blood transfusions can be a hassle. In two phase 3 clinical trials, researchers’ main goal was to see if Zynteglo could help reduce the need for blood transfusions.
The two studies (Study 1, Study 2) included 41 kids and adults younger than 50 years old with transfusion-dependent beta-thalassemia. After receiving Zynteglo, about 89% of people were able to avoid blood transfusions over a 12-month (1 year) period. They were able to maintain an ideal hemoglobin level during this time, too.
Zynteglo wasn’t compared to another medication or treatment in these studies.
What are the known side effects of Zynteglo?
Every medication has its drawbacks, including Zynteglo. In Zynteglo’s clinical trials, these side effects happened in more than 20% of people:
Mouth sores
Nausea and vomiting
Diarrhea
Constipation
Cough
Headache
Hair loss
Nose bleeds
Stomach pain
Muscle and bone pain
Skin rashes and itchy skin
Small patches of skin color changes
Smaller appetite than normal
More serious side effects have also been reported. Your care team will monitor you for side effects like these during and after your Zynteglo infusion:
Neutropenia (low white blood cell numbers)
Febrile neutropenia (low white blood cell numbers alongside a fever)
Low platelets
Low red blood cells
A higher risk for bleeding
Allergic reactions, including swelling of the face, tongue, or throat
No cases have been reported, but there’s also a chance of developing blood cancer after receiving Zynteglo. Your care team may check in annually for at least 15 years to monitor for any signs of cancer.
How much will Zynteglo cost?
Zynteglo was initially approved in Europe in June 2019. At the time of that approval, its list price was set at $1.8 million. More recently, its U.S. list price was reported as $2.8 million. This would make it the most expensive medication in the country.
This is comparable to another gene therapy medication, Zolgensma (onasemnogene abeparvovec-xioi). This one-time spinal muscular atrophy medication costs more than $2 million.
There should be ways to save on Zynteglo, but specific details are being sorted out. Zynteglo’s manufacturer, bluebird bio, is still talking to insurance companies and the government about what coverage options may look like. This is a developing situation.
Bluebird bio’s patient assistance program, my bluebird support, may also connect you to savings opportunities. For more information, visit the program online or call them at 1-833-888-6378.
When will Zynteglo be available?
Zynteglo should be available in the U.S. in the coming months. Zynteglo’s manufacturer plans on kicking off the Zynteglo preparation process for affected people in late 2022. Initial Zynteglo doses should be administered in early 2023.
However, Zynteglo won’t be available everywhere. It will only be available at certain qualified treatment centers. The location of these treatment centers will be announced starting in September 2022.
The bottom line
Zynteglo is the first gene therapy medication approved for severe beta-thalassemia in kids and adults. In clinical trials, Zynteglo helped about 89% of people avoid blood transfusions over a 12-month period. But it has side effects to keep in mind, and access concerns are being sorted out. First doses are expected to be given in early 2023.
If you have beta-thalassemia, your healthcare provider can tell you if Zynteglo is a treatment option for you.
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References
Bajwa, H., et al. (2022). Thalassemia. StatPearls.
Bluebird bio, Inc. (2022). A study evaluating the efficacy and safety of the LentiGlobin® BB305 drug product in participants with transfusion-dependent β-thalassemia, who do not have a β0/β0 genotype. ClinicalTrials.gov.
Bluebird bio, Inc. (2022). A study evaluating the efficacy and safety of the Lentiglobin® BB305 drug product in participants with transfusion-dependent β-thalassemia. ClinicalTrials.gov.
Bluebird bio, Inc. (2022). Zynteglo [package insert].
Centers for Disease Control and Prevention. (2022). Thalassemia: Complications and treatment.
Dunleavy, K., et al. (2021). With the pricing situation 'untenable' in Europe, Bluebird will wind down its operations in the 'broken' market. Fierce Pharma.
Kansteiner, F. (2022). Update: Bluebird bio's $2.8M gene therapy Zynteglo wins FDA backing. Will its US launch take flight? Fierce Pharma.
My bluebird support. (n.d.). Find a qualified treatment center.
My bluebird support. (n.d.). My bluebird support.
National Center for Advancing Translational Sciences Genetic and Rare Diseases Information Center. (2021). Beta-thalassemia.
Roy, M. (2022). Bluebird's $2.8 million gene therapy becomes most expensive drug after U.S. approval. Reuters.
U.S. Food and Drug Administration. (2022). Development and approval process | Drugs.
U.S. Food and Drug Administration. (2022). FDA approves first cell-based gene therapy to treat adult and pediatric patients with beta-thalassemia who require regular blood transfusions.
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