Is Gene Therapy the Future of Medicine?

Gene therapy is a technique that modifies a person’s genes to treat or cure disease through several mechanisms that can include replacing a disease-causing gene with a healthy copy, inactivating a disease-causing gene that is not functioning properly, or introducing a new or modified gene into the body to treat the disease.

During another session at Specialty Connect, Susan Trieu, PharmD, director of enterprise specialty clinical solutions at MedImpact Healthcare Systems, Inc., in Southlake, Texas, discussed currently approved gene therapies and gave a look at the pipeline.

Approved gene therapies include tisagenlecleucel, axicabtagene ciloleucel, and voretigene neparvovec. Tisagenlecleucel is approved for those ≤25 years with relapsed/refractory B-cell precursor acute lymphocytic leukemia and in adults with relapsed/refractory large B-cell lymphoma. This therapy made $76 million in 2018 sales, and there are approximately 90 treatment centers equipped for administration. Axicabtagene ciloleucel is approved to treat adults with relapsed/refractory diffuse large B-cell lymphoma. This therapy made $263 million in 2018 sales, and there are approximately 74 authorized treatment centers. Voretigene neparvovec is approved for patients with confirmed biallelic RPE65 mutation-associated retinal dystrophy. Product sales were $27 million in 2018, and 75 vials have been shipped so afar.

She then discussed the cautionary tale of alipogene tiparvovec, a gene therapy to reverse lipoprotein lipase deficiency—a rare inherited disorder that only affects about one in a million people. The therapy was approved in Europe in October 2012, but by April 2017, the manufacturer decided to no longer market the therapy due to lack of market demand. The company was bearing the full costs of maintaining manufacturing capabilities, managing development and validation of numerous assays, and supporting regulatory interactions and inspections. These requirements were deemed too expensive to continue production.

Dr. Trieu then discussed the gene therapy pipeline, noting that the majority of products in development are for oncology indications. Chimeric antigen receptor (CAR) T-cell therapies have shown promise in hematology and may have a potential impact for solid tumors. There are three CAR T-cell therapies in the pipeline for multiple myeloma; another for pancreatic, gastric, and prostate cancers; and another for chronic lymphocytic leukemia. Various other gene therapy products in phase III development are for indications such as choroideremia, Leber hereditary optic neuropathy, cerebral adrenoleukodystrophy, and heart failure.

She highlighted four gene therapies that may be approved in 2019 or 2020, including:

  • Onasemnogene abeparvovec (AVXS-101) for spinal muscular atrophy
  • Valoctocogene roxaparvovec (BMN 270) for hemophilia A
  • Lentiglobin for beta thalassemia
  • GT-AADC for AADC deficiency gene therapy

The adoption of gene therapy for a particular patient will depend of multiple factors, including the disease severity, durability of gene therapy, size and demographic of treatable population, current and future treatment options, relative efficacy and safety of the drug, medical and patient advocacy support, and the price of treatment.