Navigating the Emerging Challenges of Gene Therapy

During a session at the AMCP 2018 Annual Meeting, Nicole Trask, PharmD, clinical consultant pharmacist at the University of Massachusetts, discussed the challenges payers will face as gene therapies gain popularity and feasibility across a larger range of conditions.

Dr Trask started her presentation by reviewing the clinical definition for gene therapies. She explained that gene therapy is often confused with cell therapy, but that they are not the same thing. She described gene therapy as “administration of genetic material to modify or manipulate the expression of genes or alter the biological properties of living cells.”

Dr Trask also explained that gene therapy is not a new concept. The idea was posited in the 1960s with the first trials started in 1990s. She explained that deaths that resulted from inadequate safety protocol in early gene therapy trials led to this class being heavily regulated by the FDA. A trial in 1999 resulted in the death of one patient after an adenovirus vector gene therapy—while another gene therapy trial in 2000 successfully cured two patients of SCID-X1 disease, three patients in the cohort developed leukemia as a result of the treatment.

In order to demonstrate the barriers that have to be overcome to bring a gene therapy to the market, Dr Trask outlined some of the challenges of gene therapy development. She explained that precision is a major challenge, because gene therapies must target a specific set of cells in a specific region of the tissue. She noted that delivery to the incorrect cells or tissue could be catastrophic.

Another challenge highlighted by Dr Trask included the fact that use of gene therapies disrupts the normal processes of the body. This means that gene therapies often have highly toxic side effect profiles, which need to be weighed against the benefit gained by the drug. Furthermore, this challenge requires that development efforts are put into delivery vectors that are capable of targeting lower-risk cell locations.

Dr Trask also highlighted the cost issues currently surrounding gene therapies, as they have recently come to the market with total health care costs exceeding $1 million in some cases. This is compounded by the fact that the diseases currently treated by gene therapy are very rare, which increases the need for manufacturers to price the drug at a level that will make it profitable.

According to Dr Trask, as of 2015 there are 2335 gene therapy clinical trials that are either approved, completed, or ongoing, with 67% of these in the United States. Dr Trask highlighted a few gene therapies in late-stage development, including valoctocogene roxaparvovec to treat hemophilia A, EB-101 to treat recessive dystrophic epidermolysis bullosa, GS010 to treat leber hereditary optic neuropathy, elivaldogene tavalentivec to treat cerebral adrenoleukodystrophy, and RT-100 to treat heart failure.

Dr Trask concluded her presentation by emphasizing the significant challenges that gene therapies present for payers. With costs ranging from $700,000 to $1 million per patient, payers will have to develop and embrace innovative payment models in order to handle the influx of gene therapies to the market in the coming years.

According to Dr Trask, this will require assessing the value of gene therapies and the off-setting of costs that would have been incurred through standard treatment. Dr Trask added that pharma companies are beginning to understand that the pricing for threshold may be too high for payers to handle the cost burden, and that she expects costs to differ based on indication.

“In the current climate, manufacturers are becoming increasingly aware and are considering the cost that payers in the United States are willing pay,” she said during the presentation. “I also think we can expect to see differences in the cost based on the indication that the therapy is designed to treat. For example a gene therapy intended to treat heart failure, a more prominent disease state, might be significantly less costly.”

Dr Trask also noted that payers will have to closely manage sites of care in order to ensure that appropriate specialists and medical centers are available to patients during administration and during the post-treatment phase when side affects will have to be managed.

—David Costill