APR Nov/Dec 2022 - 49

« BIOPHARMACEUTICALS
Source: Food & Drug Administration. Available at https://www.fda.gov/vaccines-blood-biologics/cellular-gene-therapy-products/what-gene-therapy
Figure 2.
Bacteria can be modified to prevent them from causing infectious
disease and then used as vectors (vehicles) to carry therapeutic genes
into human tissues.
Human gene editing technology maintains a goal to disrupt harmful
genes or to repair mutated genes.6
Two Categories of Gene Therapies
There are two main ways to deliver gene therapy: ex vivo and in vivo
methods. The in vivo gene therapy approach as illustrated above
(Figure 2) means that therapy is administered directly to the patient
and the targeted cells remain in the body of the patient.4
This
methodology involves use of a gene inserted into a viral envelope,
often an adeno-associated virus (AAV). The gene-carrying virus is
prepared in a laboratory and delivered to the target organ either
by an injection or a simple infusion, where it is taken up by cells in
target organs. While it is not integrated into the chromosome, it does
appear to have a sturdy and long-lasting response, especially in slowly
replicating cells like retinal cells, or neurons. Luxturna and Zolgensma
are examples of in vivo gene therapies.
With the ex vivo approach, the targeted cells are removed from the
patient and gene therapy is administered to the cells in vitro before
they are returned to the patient's body. Target cells containing the
faulty or missing genes are extracted from the patient in a clinical
setting, such as the hospital, and the cells are re-engineered in the
laboratory to integrate a new or functional gene into the chromosome.
The reprogrammed cells are then infused into the patient and the new
gene is distributed through the patient's system as these cells multiply.
Examples of the ex vivo approach are chimeric antigen receptor T-cell
(CAR-T) therapies such as Abecma (idecabtagene vicleucel), Breyanzi
(lisocabtagene maraleucel), Kymriah (tisagenlecleucel),
(brexucabtagene autoleucel) and Yescarta (axicabtagene ciloleucel).
Tecartus
Gene Therapy Issues, Challenges
and Concerns
Gene and cell therapies are prime examples of hyper-innovation that
is needed and will benefit people with rare diseases who have been
sidelined for too long with little to no treatment options. In fact, many
rare disease patients use drugs off-label based on limited data because
they have no better options available (Figure 3). While these therapies
offer hope and represent a revolutionary step forward in the potential
treatment of many previously incurable diseases, they present huge
affordability challenges and carry very exorbitant up-front costs with
no cost-minimization, elimination guarantees or impact on quality of
life. Multi-million dollar price tags are becoming more common, as the
FDA recently approved Skysona9
for a rare neurological disorder called
cerebral adrenoleukodystrophy at a list price of $3 million.
Another concern is the longevity of response to the product, since it
may be too early to tell how long the effects of the treatments will last:
restored vision, disease remission or other may endure for a lifetime
versus a specific time period. This is particularly problematic since
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APR Nov/Dec 2022

Table of Contents for the Digital Edition of APR Nov/Dec 2022