Trends and Transformation: Gene Therapies in Rare Blood Disorders

Gene therapies are revolutionizing treatment for hemophilia A and sickle cell disease; however, uptake is slow due to hefty price tags and limited patient populations.

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Gene therapies are changing the treatment landscape for rare blood disorders. Two posters presented at the American Society of Health-System Pharmacists Midyear Clinical Meeting 2024, held Dec. 10-14, 2024, in New Orleans, La., dove into the research into gene therapies and their impact in hemophilia A and sickle cell disease.

In the first poster, authors from the Rutgers University Ernest Mario School of Pharmacy conducted a literature search between July and September 2024 for currently approved and potential pipeline therapies in phase 3 clinical trial to treat hemophilia A. They included 6 gene therapies in their review.

Currently, there is only 1 approved gene therapy for hemophilia A. Roctavian (valoctocogene roxaparvovec-rox from BioMarin Pharmaceutical) was approved in June 2023 with a price tag of $2.9 million. The one-time, single-dose infusion replaces the function of the mutated clotting factor VIII (FVIII)and allows people with severe hemophilia A to produce their own FVIII, which limits bleeding vessels.

Roctavian showed a 98.6% reduction in FVIII concentrate usage and an 83.3% reduction in treated bleeding after patients received the gene therapy infusion. With three years of follow-up data, patients receiving the infusion had an improvement in quality of life based on the Haemophilia-Specific Quality of Life Questionnaire for Adults Total Score.

There are two gene therapies that had concluded phase 3 trials: SCT800 and simoctocog alfa. The research on these two therapies showed “notable efficacy and favorable safety profiles,” the authors wrote. In addition, giroctocogene fitelparvovec, dirloctocogene samoparvovec and fidanacogene eleparvovec are all in ongoing phase 3 trials.

However, despite the expensive price tag for Roctavian, the authors noted that profitability on these therapies remains limited because of the small patient population eligible. Despite $60 million in development costs for Roctavian, only one patient was treated in 2023 and three patients in 2024, bringing in revenue of approximately $4.3 million.

“Further research is needed to evaluate the benefit of the investigational therapies and their role in the changing landscape of hemophilia A management,” the authors wrote. “Additionally, the pharmaceutical industry’s business decisions will continue to assess the impact of cost and profitability in this rare disease space.”

In the second poster, authors from the Nova Southeastern University Barry and Judy Silverman College of Pharmacy conducted a literature review to identify randomized clinical trials evaluating gene therapies in sickle cell disease. They included two studies: one for Casgevy (exagamglogene autotemcel) and the second for Lyfgenia (lovotibeglogene autotemcel).

Casgevy (Vertex Pharmaceuticals) and Lyfgenia (bluebird bio) were both approved a year earlier in December 2023. Casgevy is a one-time gene therapy that uses the patient’s own hematopoietic stem cells, which are edited using CRISPR/Cas9 technology and then infused back into the patient. It had a second indication approved a month later for beta thalassemia. Lyfgenia is also a one-time treatment that adds functional copies of a modified form of the β-globin gene into a patient’s own blood stem cells so they can produce their own hemoglobin. Both carry hefty price tags: $2.2 million for Casgevy and $3.1 million for Lyfgenia.

Casgevy’s trial included 44 adults and adolescents with sickle cell disease with a 24-month follow-up period. Lyfgenia was evaluated in a 24-month trial with 32 patients with sickle cel disease and a history of vaso-occlusive events. The mean age for both studies ranged from 22 years to 24 years, between 52% and 63% were male, and 87% to 97% were Black.

Both studies had a high rate of an absence of severe vaso-occlusive crises (97%-99%) with no hospitalizations and hemoglobin levels at normal levels during follow up. The side effects were mostly mild for both therapies.

“The current results of both trials highlight the blossoming of a new frontier in gene therapy-based sickle cell disease treatment from its inception back in the 1980s; nevertheless, one can safely state that there is much research into the long-term efficacy of both therapeutic agents left to conduct,” the authors concluded.

Uptake of both Casgevy and Lyfgenia have been slow in the real world. As of mid-2024, 20 patients had initiated Casgevy and only four had started Lyfgenia, Kevin Niehoff, an associate director at IPD Analytics who specializes in gene therapies, told Managed Healthcare Executive^® at the AMCP Nexus 2024 meeting.

Gene therapy for hemophila had similar “low and slow uptake,” he said. In addition to Roctavian for hemophilia A, Hemgenix (etranacogene dezaparvovec-drib; CSL Behrin) is a gene therapy approved for hemophilia B. Hemgenix’s price is $3.5 million.