Twenty years ago, the FDA halted all gene therapy clinical trials based on reports from France of cancers in children who received gene therapy. When last week, it was reported that deadly cancers emerged within 2 years in seven out of 67 children who received an FDA-approved gene therapy, the Agency took a wait and see approach. What changed the FDA’s perspetive on the risk of gene therapy this time around?
Bluebird’s gene therapy is one of the most expensive treatments approved by the FDA at almost $3 million per treatment. The treatment is intended for a rare and fatal genetic disease known as cerebral adrenoleukodystrophy (ALD). It was reported that about 10% of the children treated with this gene therapy developed fetal blood cancer within 1-2 year of receiving the treatment. The link between the treatment and cancer is clear, and more treated children are expected to develop similar cancers. This comes at the heal of the reports that another expensive treatment, CAR-T, leads to cancer as well. This puts the FDA at a very precarious and seemingly contradictory scenario with no good solutions but compromises.
In the twenty years since the original reports of gene therapy-related cancers, the science of cell therapy has come a long way. Numerous scientific developments have tried to address the safety issues, multiple clinical trials have evaluated these therapies for a variety of indications, and regulatory standards have been developed regarding acceptable risks. Cell and gene therapies have been approved for rare, life-threatening diseases. It is accepted that with an alternative of definitive death due to the target disease, the extension of life, even with the risk of cancer, is acceptable. Based on this premise, the FDA has decided to not withdraw approved gene therapies or CAR-T therapies.
The treatments not yet approved have been asked to conduct additional evaluations of potential carcinogenicity but with the likelihood of detecting a cancer within a typical clinical trial timeline being almost impossible, events like the ones describe above will recur and become an acceptable risk. This also demonstrates that gene therapies are far from being acceptable for the treatment of non-life threatening genetic disease and disorders due to the high risk of treatment-emergent cancer.
