Gene and cell therapy is a promising approach to treat and potentially cure various inherited diseases, especially those that affect the immune system or metabolism. However, developing and commercializing these therapies is not easy, as they face many challenges such as small patient populations, complex manufacturing processes, high costs and regulatory hurdles.
Gene and cell therapy to attract attention in the field of rare diseases are:
- Gene and cell therapy can provide effective and specific treatments for many rare diseases that lack approved therapies or have limited treatment options.
- Gene and cell therapy can target the molecular basis of rare diseases by correcting or replacing defective genes or cells.
- Gene and cell therapy can use autologous cells (from the patient) to avoid immune rejection or graft-versus-host disease that may occur with allogeneic cells (from a donor).
- Gene and cell therapy can offer long-term or even permanent benefits with a single administration.
- Orphan drug designation, which grants special status to drugs for rare diseases and provides incentives such as fee waivers, tax credits, scientific advice and protocol assistance.
- Marketing authorization, which grants approval for orphan drugs to be marketed and sold in a country or region, sometimes with conditional or accelerated pathways.
- Marketing exclusivity, which grants a period of market protection for orphan drugs from competition by similar drugs.
- Pricing and reimbursement, which determines the price and level of coverage for orphan drugs by health systems or insurers, sometimes with special arrangements such as risk-sharing agreements or managed entry agreements.
What are some examples of cell gene therapy for rare diseases?
Cell gene therapy has been applied to several rare diseases, mostly affecting the immune system or metabolism. Some examples are:
- Adenosine deaminase severe combined immunodeficiency (ADA-SCID): This is a life-threatening condition caused by a lack of an enzyme called adenosine deaminase, which leads to severe infections and failure of multiple organs. Cell gene therapy involves using a retroviral vector to deliver a functional ADA gene into the patient's HSCs. This was the first cell gene therapy to receive marketing authorization in Europe in 2016 under the name Strimvelis. However, in 2021, the commercial sponsor announced that it would discontinue investment in this program due to low demand and high costs.
- Beta-thalassemia: This is a blood disorder caused by reduced or absent production of beta-globin, a component of hemoglobin that carries oxygen in red blood cells. This leads to severe anemia and organ damage. Cell gene therapy involves using a lentiviral vector to deliver a modified beta-globin gene into the patient's HSCs. This has shown remarkable efficacy in clinical trials, with many patients achieving transfusion independence and normal hemoglobin levels. This therapy received conditional approval in Europe in 2019 under the name Zynteglo, but its launch has been delayed due to manufacturing issues and reimbursement negotiations.
- Sickle cell disease (SCD): This is another blood disorder caused by mutations in the beta-globin gene that result in abnormal hemoglobin that forms sickle-shaped red blood cells. This causes chronic pain, organ damage and increased risk of infections and strokes. Cell gene therapy involves using CRISPR-Cas9 to edit the patient's HSCs to increase the production of fetal hemoglobin, which can compensate for the defective adult hemoglobin. This has shown impressive results in early clinical trials, with reduced pain crises and improved quality of life.
