Gene Therapy Pipeline: Top Diseases that Could Reap Positive Benefits


Gene therapy, which got its start in the 1960s, is finally starting to take hold.

Nicole Trask, PharmD, clinical consultant pharmacist at University of Massachusetts Pharmacy Services in Shrewsbury, MA, opened her session at the Academy of Managed Care Pharmacy Managed Care and Specialty Pharmacy (AMCP) Annual Meeting, in Boston April 24, by defining gene therapy as the administration of genetic material to modify or manipulate the expression of genes or alter the biological properties of living cells. She added that gene therapy can be used to accomplish one of the following actions:

  • Introduce a new or modified gene to treat disease
  • Replace a disease-causing gene with a healthy copy of the gene
  • Inactivate a disease-causing abhorrent gene

The first clinical study on gene therapy, which included five participants, was published in 1990. In that study, a retroviral vector was used to transfer a neomycin resistance marker gene into tumor-infiltrating lymphocytes for the treatment of metastatic melanoma. In the study, lymphocytes were removed and expanded, she said.

Trask attributed gene therapy’s slow clinical progress largely to safety concerns and vector inefficiencies.

One of the challenges with gene therapy is the need for precision in delivery to the appropriate cells and/or tissues. Further, the gene must be either activated or remain inactivated. Delivery to the wrong cells and/or tissues could be catastrophic.

That’s why focusing on safety is wise. In 1999, one patient died after experiencing an adenovirus gene transfer in ornithine transcarbamylase deficiency, a rare genetic disorder characterized by a complete or partial lack of the enzyme ornithine. And in 2000, two patients with SCID-XI, an inherited disease impacting the immune system, were successfully treated using the MoMLV vector; these were two of 11 patients involved in the clinical trial, where three patients developed leukemia as a result of the gene transfer procedure, according to Trask.

Gene therapy current focus

Investigational indications for gene therapy include conditions such as:

  • ALS
  • Batten disease
  • Heart failure
  • Sickle cell disease
  • Hemophilia A and B
  • Oncology
  • Tay-Sachs disease

FDA approved in 2017 Luxturna (voretigene neparvovec-rzyl) for the treatment of confirmed biallelic RPE65-mediated retinal dystrophy. The treatment, which is associated with significant improvements in functional vision, costs $425,000 per eye, or $850,000 for most patients, she added.

Trask also highlighted gene therapies that are in late-stage development, including:

  • Valoctocogene roxaparvovec for hemophilia A. Awarded breakthrough therapy and orphan drug designations by FDA; one phase 3 clinical trial started in December 2017 and another phase 3 clinical trial will begin this year.
  • EB-101 for recessive dystrophic epidermolysis bullosa, which causes very frail skin that easily blisters or erodes in response to minor injury or friction; young adults with this condition are at increased risk of squamous cell carcinoma. Awarded regenerative medicine advance therapy, breakthrough therapy, orphan drug, and rare pediatric disease designations, this therapy will be involved in a phase 3 trial that’s currently recruiting patients and expected to launch this year.
  • GS010 for Leber hereditary optic neuropathy, which causes severe and irreversible loss of vision and blindness by early adulthood. Two clinical phase 3 trials are ongoing with topline results expected in April 2018 and the third quarter of 2018, respectively.
  • Elivaldogene tavalentivec for childhood cerebral adrenoleukodystrophy, which leads to the loss of neurologic function and death. Final data collection for a phase 2/3 clinical trial is expected in August 2019.
  • RT-100 for heart failure. Awarded fast track designation, this therapy is in the midst of a phase 3 clinical trial, which is expected to be completed in February 2022.

While expressing enthusiasm for these therapies, Trask also noted their challenges for payers, including their extremely high costs-as much as $700,000 to $1,000,000 per patient-and the reality that some gene therapies may be associated with safety risks.

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