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October 13, 2022

News about All Segments | Rx

Gene replacement therapy updates

In 2017, the U.S. Food and Drug Administration (FDA) approved Luxturna®, the first gene replacement therapy. At the time, a flurry of gene‑based therapies was predicted to hit the market over the next few years. But by 2019, only one other gene replacement therapy was on the market.

Now, it seems, the FDA is moving full speed ahead, having approved two new gene replacement therapies within a few weeks of each other: ZyntegloTM and Skysona®. Both Zynteglo and Skysona are one‑time infusions that are eligible for coverage under the medical benefit for members who meet the coverage criteria in our medical policies.


In August, the FDA approved Zynteglo (betibeglogene autotemcel) to treat severe beta thalassemia in adults and children. Beta thalassemia is caused by a genetic mutation that limits the amount of oxygen red blood cells can carry. This condition can lead to chronic weakness, dizziness, and organ damage. Every year, about 60,000 people worldwide are diagnosed with beta thalassemia, with cases ranging from mild to severe.

Zynteglo uses the patient's cells to create new, working cells that gradually restore red blood cell function and improve oxygen circulation in the body. Prior to this approval, the two treatment options for severe beta thalassemia were lifelong blood transfusions or stem cell transplant. These options both have risks, and it can be challenging to find a matching stem cell donor.


In September, the FDA approved Skysona (elivaldogene autotemcel) to treat cerebral adrenoleukodystrophy (CALD) in children younger than 18 who are not candidates for stem cell transplant. With CALD, there is a dysfunction in the genes responsible for creating proteins that break down very long‑chain fatty acids. When these acids build up, they destroy the protective covering for the nerves in the brain and spinal cord, leading to progressive loss of cognitive abilities and muscle control. Most cases are fatal within ten years of diagnosis. Approximately 1 in 21,000 male newborns are diagnosed worldwide each year.

Skysona uses the patient's cells to create working copies of the gene responsible for producing the proteins that break down the very long‑chain fatty acids. It is important to note that Skysona cannot reverse existing neuromuscular damage; it can only prevent future damage. Prior to this approval, the only treatment for CALD was stem cell transplant, which comes with serious risks and challenges.

Skyrocketing costs

A one‑time dose of Zynteglo is slated to cost about $2.8 million, and a one‑time dose of Skysona is projected at $3 million. Although there are only four gene replacement therapies on the market right now, as many as ten more could receive FDA approval in the next few years. This drug class will continue to push the cost envelope, as each approved gene replacement therapy has exceeded the cost of the gene replacement therapy that preceded it.

Independence recognizes that the traditional management strategies we are using to manage this class (such as medical policy and precertification) will not be enough to minimize future financial impact.

In response, Independence is pursuing other strategic solutions, which may include the following options:

  • Harnessing the capabilities of the high‑quality, valued‑based facilities in our network that have access to these advanced therapies and a reputation for optimizing their delivery to adult and pediatric populations
  • Exploring outcomes‑based agreements with drug manufacturers, where the drug manufacturer provides significant reimbursement if the member does not meet certain therapeutic metrics after treatment

Supporting our members

The health care professionals on our Case Management team engage, educate, and support all our members. Since genetic conditions often come with additional stress and complexity, Independence has a dedicated team of registered nurses who specialize in gene‑based diseases and therapeutics. This team coordinates precertification reviews, answers questions, identifies resources, and helps members navigate all aspects of the treatment process.

Looking ahead

Gene replacement therapy has the potential to be life‑changing for patients, and our health plans will need to keep evolving to innovatively manage this dynamic drug class. Independence will harness our network capabilities and key partnerships across the industry to build modern solutions that focus on clinical experience, value, safety, and patient‑centered care. Keep following Independence Edge for more information on these initiatives.            

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Independence Blue Cross offers products through its subsidiaries Independence Hospital Indemnity Plan, Keystone Health Plan East and QCC Insurance Company, and with Highmark Blue Shield — independent licensees of the Blue Cross and Blue Shield Association.