Gene therapies—medications that involve directly editing or replacing a patient’s genetic material to treat disease—have been discussed in the scientific community for more than half a century. But while gene therapies only began receiving approval in 2017, there are now more than 900 currently in the pipeline, with an estimated 10-20 slated for approval each year by 2025.
Many of the diseases with an approved gene therapy have few, if any, treatment options, so this is potentially life-changing news for those who suffer from these particularly rare conditions. While many questions remain about gene therapy, including duration of effectiveness (also known as “durability”), it is clear that they offer significant promise for patients with a number of debilitating disorders.
Here are a few specialty conditions with noteworthy gene therapies to watch for in the 2023 pipeline.
Treatment for Duchenne muscular dystrophy: SRP-9001
One condition with a gene therapy in development is Duchenne muscular dystrophy (DMD), an inherited disorder that is caused by a defective gene for dystrophin, a protein important for muscle fiber. DMD primarily affects young males (about 1 in 3,600 males born in the U.S.), and leads to progressive weakening and loss of muscle, with a range of symptoms including difficulty walking, cardiomyopathy and even learning disabilities. These health complications become fatal as they advance, and many DMD patients do not live past their twenties.
The primary treatment for DMD is the use of corticosteroids like deflazacort or prednisolone to delay muscle loss. Other supportive options include physical therapy to prevent contractures and gentle exercise to prevent muscle atrophy. None of these therapies are curative, and they can be prohibitively expensive: deflazacort costs $35,000 annually for a child weighing 55 pounds, and because the dose increases with a patient’s weight, the cost can exceed $100,000 per year.
Because these treatments are often ineffective, costly and can cause disruptive side effects, there is a lot of hope for SRP-9001, a new gene therapy for DMD nearing the market. SRP-9001 uses an inactivated virus to deliver a version of dystrophin to the patient’s muscle cells to recode them and create healthy dystrophin. Thus far, treatment has shown increased motor function and walking ability for DMD patients after three years. SRP-9001 currently has a U.S. Food and Drug Administration action date of May 2023, but may be delayed.
Treatment for recessive dystrophic epidermolysis bullosa: Vyjuvek®
Recessive dystrophic epidermolysis bullosa (RDEB) is a rare genetic condition with a gene therapy, Vyjuvek, nearing approval this year. RDEB is caused by mutations in the COL7A1 gene, which helps form a protein important to the strength and health of skin called type VII collagen. Those affected by RDEB (about 3,000 patients in the U.S.) experience painful blistering skin erosions and severe scarring. Current treatments for RDEB are limited: pain relievers and routine wound and infection care form the backbone of treatment.
Two things differentiate Vyjuvek from other gene therapies that have been approved: it is topical and it can be redosed. Where other gene therapies may require visits to surgical centers for one-time procedures, Vyjuvek is a gel that can be applied and re-applied directly to a patient’s wounds. The gel uses inactive viral cells to deliver healthy versions of the COL7A1 gene to the skin, restoring type VII collagen. This improves healing and prevents blistering. In clinical trials, all wounds treated with Vyjuvek healed satisfactorily for at least three months. While the exact pricing is unknown, it’s expected to cost between $100,000-$300,000 per year, in line with the current cost of managing the disease.
Treatments for sickle cell disease and beta thalassemia: Exa-Cel
Approximately 100,000 Americans have SCD, and 1 in 365 African American children are born with SCD. Currently, the only cure is a bone marrow transplant or stem cell replacement. SCD is an inherited disease affecting hemoglobin, a protein that carries oxygen in red blood cells. Malformed hemoglobin changes the overall shape of a patient’s red blood cells. These sickled cells cause pain, can burst easily and may stick to vessel walls, leading to problems like anemia, infection or stroke.
TDT (affecting approximately 1,200 people in the U.S.) is another inherited blood disorder, where lack of a protein chain called beta-globin affects a patient’s hemoglobin production and can cause severe symptoms such as anemia, enlarged vital organs, delayed puberty, blood clots and more. Frequent, lifelong blood transfusions are required for people with TDT.
Exa-cel is an “ex vivo” therapy, meaning the treatment takes place outside of the body: the patient’s stem cells are removed, their genetic makeup is modified to increase the production of healthy hemoglobin and then treated stem cells are administered to the patient. The cost of treatment has not been announced, but is speculated to be in the millions.
Hemophilia gene therapies: RoctavianTM and Hemgenix®
Hemophilia is a disorder caused by the lack of a clotting protein called factor, which is vital to controlling bleeding. Hemophilia mostly affects males (approximately 30,000 in the U.S.)1, and the two most common types are hemophilia A and hemophilia B, caused by insufficient factor VIII and IX respectively.
Traditional management for hemophilia involves treatment with plasma-derived or recombinant factor. However, gene therapies for hemophilia will soon be available, including:
- Hemgenix (approved 2022) for hemophilia B
- Roctavian (anticipated approval summer 2023) for hemophilia A
What’s notable about hemophilia is that the existing treatment landscape is relatively robust and highly effective compared to diseases like DMD and RDEB. Gene therapies for hemophilia will be initially limited to patients with more severe disease. Uncertain durability, combined with a continued need for periodic factor treatment for trauma or accidents and price tags in the $2.5-3.5 million range means that gene therapies will not be a mainstay of treatment for most hemophilia patients in the near future.
As more gene therapies are approved, plan sponsors will need to determine the likelihood these treatments will impact their benefit, and prepare for the expense and necessary coverage decisions. This is especially true because many gene therapies will be for rare disorders with few or no treatment options available.
Since there are a number of very effective hemophilia treatment options already available, the outlook is different. Plan sponsors will need to make coverage decisions for gene therapies based on unique hemophilia patient needs and those specific clinical considerations.
Plan sponsors should work with a specialty partner that has the proven ability to navigate the complexities of gene therapy distribution, storage and dispensing and has the appropriate tools to manage costs and ensure visibility of utilization, such as:
- An automated payer reporting dashboard that allows an understanding of patient-specific utilization and spend history for the last 24 months
- A gene and cell therapy forecasting model that can help plans anticipate potential future expenditures
As more gene therapies become available, the ability to project potential utilization and spend along with the need for quality reporting on utilization that has occurred will be vital for plan sponsors to make more informed policy and coverage decisions.
1 Institute for Clinical and Economic Review, September 2022