In 2019, Novartis’s gene therapy Zolgensma has made news as the „most expensive single-dose drug ever“ with $2.125 million. Just 3 years later, as of November 2022, bluebird bio’s Skysona with the price tag of $3 million per dose holds the title. The development of gene therapies, often claimed to be single-dose drugs, is one of the fastest growing areas of healthcare, with over 2,000 gene therapies in development globally.
Drug manufacturers derive the higher prices from (expected) drastically different prognoses for the patient, relative simplicity of administration, one-off treatment (often as compared to the previous treatments) and associated economic and societal benefits. However, policymakers often struggle to adapt the reimbursement guidelines also because the longest clinical follow-up of treated patients is, for basically all of these, still less than a decade.
What are currently the most expensive single-dose drugs approved by FDA? And is the sky the limit when it comes to the (reimbursable) price?
1. Skysona - $3 million.
In September 2022, bluebird bio's Skysona (elivaldogene autotemcel or eli-cel) was approved as the first treatment indicated for boys 4 to 17 years of age with early, active cerebral adrenoleukodystrophy (CALD). CALD is a rare inherited and fatal neurodegenerative disease that occurs primarily in young boys (median age of onset 7 years). Nearly half of patients who do not receive treatment die within five years of symptom onset. Skysona is derived from each of the patient’s own stem cells and further processed to contain a copy of the gene to make a functional ALDP (adrenoleukodystrophy protein). Consequently, it is administered in a single infusion treatment. The clinical data point to the fact that Skysona-treated patients had an estimated 72% likelihood of Major Functional Disability (MFD)- free survival at 24 months from time of first neurologic function score (NFS) ≥ 1, compared to untreated patients who had an estimated 43% likelihood of MFD-free survival. The wholesale acquisition cost of Skysona is $3 million.
2. Zynteglo - $2.8 million
Zynteglo (betibeglogene autotemcel or beti-cel), a one-time lentiviral vector (LVV) gene therapy, was approved by the FDA in August 2022 for the treatment of adult or pediatric beta-thalassemia patients who require regular red blood cell (RBC) transfusions. Patients with beta-thalassemia often require extensive red blood cell transfusions every 2 to 5 weeks. Beta-thalassemia is a rare, inherited blood condition that can cause severe anemia and lifetime dependence on them. According to research, almost 90 percent (32 out of 36) of evaluable patients attained transfusion independence, which is defined as not requiring red blood cell transfusions for at least 12 months while maintaining a weighted average total hemoglobin of at least 9 g/dL. Based on the most recent follow-up, results were persisting. The cost of Zynteglo is $2.8 million per patient.
Importantly, following a failed European launch in th EU in 2019 due to issues with reaching reimbursement agreements in the European market, in the US the manufacturer bluebird bio and authorities have agreed on a landmark outcomes-based payment scheme depending on whether or not patients reach the key milestone of transfusion independence.
3. Zolgensma - $2.125 million
(onasemnogene abeparvovec-xioi) has been FDA-approved in May 2019 to treat pediatric Spinal Muscular Atrophy (SMA). It has held the title of the most expensive single-dose treatment until the approval of Zynteglo. The manufacturer, Novartis, estimates that the overall cost of Zolgensma in the US is $2.125 million. SMA is a rare genetic motor neuron disease that, depending on the severity, may make it difficult to breathe, hold your head up, or even swallow. Due to their inability to breathe, the majority of children with SMA do not live through early infancy. Zolgensma is administered as a single intravenous (IV) dose. It is considered to be a potentially curative treatment and functions by substituting the survival motor neuron 1 (SMN1) gene that is damaged or absent.
4. Luxturna - $850,000
In December 2017, the FDA authorized the gene therapy Luxturna (voretigene neparvovec-rzyl) to treat a rare form of the hereditary retinal illness called biallelic RPE65-mediated inherited retinal disease (IRD). A normal copy of the RPE65 gene is delivered into the eye by subretinal injection using the adeno-associated viral (AAV) vector gene therapy Luxturna. Biallelic RPE65-mediated inherited retinal disease can lead to blindness and occurs in roughly 1,000 to 2,000 people in the U.S. Luxturna has been developed by Spark Therapeutics and despite costing $850,000 (or $425,000 per eye), the manufacturer claims it is potentially cheaper than the drugs that have come before it, due to the fact that it is a one-time treatment.
Obviously, the lack of practical, long-standing experience with gene therapies beyond several years of follow-up, uncertain evidence with often small sample sizes, and the price tag make it challenging to create a unified framework for the access to these one-off treatments – which has resulted in failed access attempts in many cases already. Co-financing of the treatments through specialized funds, in conjunction with outcomes-based agreements between manufacturers and the payers alike the one reached in the case of Zynteglo might be the way forward.
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