In the realm of modern medicine, groundbreaking advancements often come at a significant cost. The development of cutting-edge gene therapies has provided remarkable solutions for individuals grappling with rare and challenging conditions. However, the high price tags associated with these treatments have sparked both fascination and controversy.
In this article, we delve into the world of the most expensive drugs, where innovative gene therapies are transforming the lives of patients facing conditions such as hemophilia B, cerebral adrenoleukodystrophy, beta-thalassemia and spinal muscular atrophy. Here's a look at the extraordinary scientific achievements and financial implications of these groundbreaking treatments.
1. Hemgenix, CSL Behring, hemophilia B
U.S. list price: $3.5 million
After the FDA approved the first gene therapy for adults with hemophilia B last year, it quickly became the world's most expensive drug, priced at $3.5 million per dose.
Australian drugmaker CSL Behring bought the rights to the drug from UniQure in 2020 for $450 million upfront, while the drug was still in phase 3 trials. Hemgenix is administered as a one-time gene therapy through IV fusion and offers an alternative to frequent Factor IX prophylaxis treatment for hemophilia patients. The FDA based its approval on positive results from the HOPE-B trial, the largest gene therapy trial for hemophilia B. In the trial, 94% of patients (51 out of 54) treated with Hemgenix were able to discontinue prophylaxis and remained free of continuous routine treatment. Hemgenix received Priority Review, Orphan and Breakthrough Therapy designations from the FDA and was granted conditional approval in the EU this past February.
While Hemgenix has shown a significant reduction in bleeding rates, it does not address the underlying mutation causing hemophilia B. In the ongoing HOPE-B trial, Hemgenix led to a substantial decrease in annual bleeds, with 94% of patients able to discontinue factor IX infusions. The mean adjusted annualized bleeding rate for all bleeds was reduced by 54% after seven to 18 months of Hemgenix treatment.
2. Elevidys, Sarepta, Duchenne muscular dystrophy
U.S. list price: $3.2 million
Sarepta Therapeutics, a rare disease drugmaker, recently received accelerated FDA approval for SRP-9001, which will be marketed as Elevidys. This gene therapy, based on adeno-associated virus, is now approved for the treatment of ambulatory pediatric patients aged 4 through 5 years with Duchenne muscular dystrophy (DMD) who have a confirmed mutation in the DMD gene.
The approval was based on data from three ongoing clinical studies, with a wholesale acquisition cost of $3.2 million, making it the second most expensive prescription drug currently available. Duchenne muscular dystrophy is a rare, life-threatening disease affecting approximately 1 in every 3,500-5,000 newborn boys annually.
3. Skysona, bluebird bio, cerebral adrenoleukodystrophy
U.S. list price: $3 million
The FDA granted Accelerated Approval to bluebird's gene therapy, eli-cel, marketed as Skysona, in September 2022. The therapy is now authorized for the treatment of early, active cerebral adrenoleukodystrophy (CALD) in boys and teenagers aged 4-17.
CALD is a progressive neurodegenerative disease that primarily affects young boys, leading to various disabilities, including cortical blindness, incontinence, and loss of voluntary movement. Without treatment within five years of initial symptoms, nearly half of the patients succumb to the disease.
Skysona functions by delivering transduced hematopoietic stem cells into cerebral microglia expressing the adrenoleukodystrophy protein (ALDP), which helps produce functional protein levels in the brain. Bluebird has treated 67 patients with follow-up durations of up to seven years. After its approval, Boston Children’s Division of Hematology/Oncology Hospital Chief expressed the significance of the drug being offered at the hospital. "After supporting the clinical development of SKYSONA for nearly a decade as a study site, Boston Children’s Hospital is extremely pleased that an FDA-approved therapy is now available for children who urgently need new therapies.”
In 2021, after struggling with securing reimbursement agreements with European payers for its gene therapies, Bluebird bio announced its decision to withdraw Skysona from the European market as part of its operations wind-down in the region and to the focus on the U.S. market.
4. Zynteglo, bluebird bio, beta-thalassemia
U.S. list price: $2.8 million
The FDA gave its nod to bluebird's beti-cel, branded Zynteglo, in August of 2022, making it the first cell-based gene therapy for the treatment of adult and pediatric patients with beta-thalassemia who require regular red blood cell transfusions.
Beta-thalassemia is a rare genetic blood disease characterized by mutations in the beta-globin gene, resulting in significantly reduced or absent adult hemoglobin production. Previously, patients with the severe form had to rely on regular blood transfusions. According to a report by Research and Markets, costs of treatment for transfusion-dependent thalassemia vary across countries, ranging from $563 to $128,062. However, beti-cel's approach, which involves adding functional copies of a modified form of the B-globin gene into the patients' hematopoietic stem cells, offers hope for a transformative one time treatment options.
5. Zolgensma, Novartis, spinal muscular atrophy
U.S. list price: $2.5 million
Zolgensma is a one-time treatment that delivers a functional copy of the survival motor neuron (SMN) gene to motor neuron cells, improving muscle movement and survival in SMA patients. The drug received Fast Track, Breakthrough Therapy, Priority Review and Orphan Drug designations.
Initially developed by AveXis, Novartis got its hands on the drug through its 2018, 8.7 billion acquisition of the firm. In 2019, Zolgensma received approval as a groundbreaking treatment for infants with Type 1 SMA, but it also came with a groundbreaking price. The original cost of $2.125 million exceeded the typical cost-effectiveness threshold, as analyzed by the Institute for Clinical and Economic Review. Cost-effectiveness analysis compares costs and outcomes of policy options, using ratios to measure additional health gained per unit of resources spent. To mitigate the high price, the company introduced flexible payment models, such as spreading the cost over five years and only requiring payment if the treatment remains effective.
This approach aligns Zolgensma's annual cost with that of Spinraza, another treatment for SMA patients, during those years and has become common for expensive, one-time gene therapies in the U.S. The strategy has proven successful, with Novartis securing favorable coverage policies for Zolgensma, encompassing approximately 97% of patients with commercial insurance and 86% with Medicaid, according to the company's spokesperson.