The Top 5 Most Expensive FDA-Approved Gene Therapies

Gene Therapy

The United States Food and Drug Administration defines gene therapy as a treatment “to modify or manipulate the expression of a gene or to alter the biological properties of living cells for therapeutic use.” Gene therapy has become a critical tool for treating genetic diseases, providing lifesaving and life-changing alternatives that may eliminate the need for chronic treatments.

There are five main types of gene therapy products, including genetically engineered plasmid DNA, viral vectors, bacterial vectors, human gene editing technologies, and patient-derived cellular gene therapy products.

The first FDA-approved gene therapy in the United States, Luxturna, was a treatment for vision loss linked to congenital retinal dystrophy. Even as early as 2017, when the product was initially launched, the therapy came with a hefty price tag of $425,000 per eye for each one-time treatment.

The most FDA-approved expensive gene therapies are Hemgenix, Skysona, Zynteglo, Zolgensma, and Luxturna.

Hemgenix

Priced at roughly $3.5 million, CSL Behring manufactures the world’s most expensive drug, Hemgenix. On November 22, 2022, the FDA approved Hemgenix, the first gene therapy for adults with hemophilia B, otherwise known as congenital factor IX deficiency.

The condition affects 1 in 5,000 people, accounting for roughly 30,000 patients in the US. Hemophilia B is a genetic bleeding disorder caused by a mutation in the congenital factor IX gene, preventing the body from expressing proteins needed to clot blood or stop bleeding.

The condition’s most common symptoms include prolonged or excessive bleeding following an injury, surgery, or dental procedure; however, some bleeding episodes may occur unprompted. Left untreated, prolonged bleeding caused by this condition can impact a patient's joints, organs, and nervous system.

The standard treatment for hemophilia B is a series of frequent infusions to replace the clotting factors, maintain normal blood levels, and prevent excessive bleeding. According to the Orphanet Journal of Rare Diseases, the average direct medical cost of factor IX treatment is roughly $614,886 annually. Additional non-medical costs ranged from $2,371 to $6,931.

The Journal of Thrombosis and Hemostasis estimates that the median lifespan of a patent with hemophilia B is 77 years, bringing the lifetime direct medical costs to over $47 million.

Comparatively, Hemgenix, etranacogene dezaparvovec, is a viral vector one-time gene therapy delivered via intravenous infusion. Based on clinical trial data, the treatment can eliminate the need for repeat treatments for at least eight years, while ongoing trials follow patients for even longer. Clinical researchers hypothesize that this new gene therapy can prevent the need for regular treatments.

According to a statement by CSL Behring, the drug is anticipated to save the US healthcare system $5–5.8 million per patient treatment.

Skysona

Coming in second place, Skysona, developed by bluebird bio, was approved by the FDA on September 16, 2022. The drug treats active cerebral adrenoleukodystrophy (CALD) in males between 4 and 17.

CALD is a progressive neurodegenerative disease that can lead to cognitive and motor decline, including loss of communication abilities, cortical blindness, incontinence, wheelchair dependence, and more. The condition impacts young boys, with roughly 50% of patients dying within five years of symptom onset.

According to Adrenoleukodystrophy News, the standard treatment for CALD is an allogeneic hematopoietic stem cell transplant. While not all patients are eligible for stem cell therapy, earlier intervention may delay disease progression. Estimates from DVC Health state that the cost of a single stem cell transplant can range from $15,000 to $75,000.

Based on data from phase 2 and 3 clinical trials, treatment with Skysona increased the chance of survival by 29% for patients with CALD.

According to bluebird bio, “SKYSONA uses ex vivo transduction with the Lenti-D lentiviral vector (LVV) to add functional copies of the ABCD1 gene into a patient’s own hematopoietic stem cells (HSCs). The addition of the functional ABCD1 gene allows patients to produce the ALD protein (ALDP), which can then participate in the local degradation of very long-chain fatty acids (VLCFAs). This degradation of VLCFAs is believed to slow or possibly prevent further inflammation and demyelination.”

The drugmaker plans to follow the $3 million treatment over the next 15 years.

Zynteglo

Just months before being awarded Skysona approval, bluebird bio’s Zynteglo, gene therapy for beta-thalassemia, was approved on August 17, 2022.

Patients with this condition have mutated beta-globin genes that impact hemoglobin production, significantly reducing or eliminating hemoglobin production. While the severity of the disease varies depending on the level of hemoglobin production, one of the most severe forms of the condition is called transfusion-dependent beta-thalassemia or beta-thalassemia major, comprising up to 1,500 people in the US.

Patients with transfusion-dependent beta-thalassemia (TDT) typically undergo a lengthy blood transfusion every 2–5 weeks, as transfusions only offer a temporary solution. An article published in HemaSphere estimates an average of 16.8 transfusions yearly for patients with TDT.

Regular transfusions also increase patients’ morbidity and mortality risk, increasing the probability of cardiac, liver, and endocrine complications.

Researchers in HemaSphere estimated the average lifespan of a patient with TDT to be 39 years, amounting to a lifetime average of 686 transfusions. Based on these generalizations, the researchers calculated the average lifetime treatment cost for one patient with TDT to be roughly $5.4 million.

The treatment is one-time ex vivo LVV gene therapy, replacing regular blood transfusions for patients who require them. The treatment allows patients to create their own hemoglobin by transfusing them with genetically modified hematopoietic stem cells with a functional gene copy.

According to GoodRx, the list price for this medication is roughly $2.8 million for a one-time treatment, not accounting for hospital stays and follow-up care. While it is unclear what the final cost of treatment will be with these components, the pharmaceutical company claims it will lead to cost savings throughout a patient’s lifespan.

Zolgensma

On May 24, 2019, the FDA approved Zolgensma, onasemnogene abeparvovec, a spinal muscular atrophy (SMA) treatment.

The International Journal of Applied and Basic Medical Research notes that SMA is an umbrella term for a group of neuromuscular disorders caused by mutations in the survival motor neuron 1 gene (SMN1), which prevents the body from creating properly functioning SMN1 proteins. As a result, motor neurons cannot survive, leading to muscle weakness and — if left untreated — death.

Before Zolgensma was approved, the only available treatment for SMA was Spinraza (nusinersen), manufactured by Biogen. While Spinraza did not cure SMA, the drug slowed disease progression and improved motor function.

However, the treatment is temporary. Priced at $750,000 for the first year of treatment and $350,000 each subsequent year, the treatment must be administered every four months.

Comparatively, Zolgensma is a one-time gene therapy treatment that uses adeno-associated viral (AAV) vectors to deliver functional human SMN1 genes to patients via a single intravenous infusion. Novartis is selling the drug at $2.1 million per dose.

Luxturna

Luxturna, voretigene neparvovec-rzyl, also manufactured by Novartis, was approved by the FDA on December 18, 2017, to treat patients with retinal dystrophy caused by biallelic RPE65 mutations, a type of hereditary retinal dystrophy.

The condition affects roughly 1,000–2,000 patients in the US. A normally functioning RPE65 gene produces all-trans retinyl ester isomerase, an enzyme that facilitates the visual cycle. Absent or non-functioning forms of the enzyme cause retinal dystrophy, characterized by vision loss.

Using AAV vectors to deliver an unmutated version of the gene, Luxturna helps partially restore vision. With a one-time injection under the retina of each eye, Luxturna can improve vision in patients with some viable retinal cells. The drug costs $425,000 per eye for $850,000 per patient.

Effects of Gene Therapy Costs

Although gene therapy has proven to be a tool to revolutionize healthcare, the hefty healthcare costs associated with the treatments have made development and adoption difficult for the industry.

Theoretically, the high price of these treatments is offset by the potential lifetime cost of other, less effective therapies. Commentary in a Nature publication notes that the ability of new gene therapies to reduce healthcare costs down the line could justify their initial costs upfront.

However, with such a high upfront price, only some patients and payers can afford the medications. Steven Pearson, president of the Institute for Clinical and Economic Review, a health-economics think tank in Boston, MA, revealed that although there is no formal regulation on pharmaceutical companies’ pricing of gene therapies in the US, many hypothesize that health insurance companies and payers will restrict coverage in an interview with Nature.

As well-developed and wealthy nations flail while looking for a way to manage costs, low- and middle-income countries are left out of the discussion because drugmakers’ costs make affordability impossible.

With that in mind, many healthcare leaders are exploring alternative procedures that may reduce treatment costs. One proposed solution is to develop technologies to ease or automate the production, development, and clinical trial process.

Alternatively, researchers may consider building on existing treatment options that are FDA approved or have significant data backing their efficacy and safety.

Health economists urge industry leaders and government officials to develop more affordable funding models, improving cost-effectiveness and accessibility. The researchers warn that high therapy or drug prices may limit funding abilities and attract fewer scholars to the field.