Four days after receiving a gene therapy treatment designed to address spinal muscular atrophy, the patient grew listless.
Body weight shot up 15 percent. The liver was ballooning. The patient went into shock and had difficulty breathing and dilated pupils.
“Upon autopsy, 95 percent of the liver was degenerating, with what little structure remained clogged with clots,” wrote Ricki Lewis of the DNA Science blog. “Liver enzyme levels were through the roof, tiny clots everywhere, and a spike in cytokines indicated inflammation. Even the fat was blood-tinged, and a host of organs affected — spleen, thymus, lymph nodes, digestive organs, heart and lungs, but the central nervous system and kidneys spared.”
Fortunately, the patient was a rhesus monkey. Unfortunately, the dose it was given was the same as was given to 9 of 12 children involved in a clinical trial, and the doctor who was instrumental in developing these therapies has walked away.
Whether by replacing mutated genes with healthy copies, inactivating or “knocking out” mutated genes to allow others to function or introducing new genes to help the body fight disease, gene therapy will be part of our medical future. The possibilities of treating some inherited disorders, such as cancer and some viral infections, is truly exciting.
But, for a very good reason, the National Library of Medicine says the technique “remains risky and is still under study to make sure that it will be safe and effective.”
President Trump vowed during his State of the Union speech to finally defeat AIDS and childhood cancer — both of which could be treated with gene therapy under the right circumstances.
The president is a man of action, and he will want results quickly. But in this case, some of the results have come too quickly and, in trying to remove a bottleneck for drug and treatment approvals by the Food and Drug Administration, the government could be exposing Americans to unnecessary dangers.
It’s only been within the last two years that any gene therapies have been approved for use in the United States, and they presently are used only for diseases that have no other known cures.
But activity is ramping up quickly.
Already, the FDA has about 800 Investigational new drug applications for cell and gene therapies in the pipeline, with many more on the way. It expects to receive up to 200 applications per year, starting next year, and to approve 10 to 20 cell and gene therapies every year from 2025 forward.
Saying “a turning point” has been reached on gene therapy, the agency announced plans earlier this year to add up to 50 additional clinical reviewers to the group that oversees clinical investigation, development and review of these products. It also plans to update policy guidance and make use of “accelerated approval pathways” that will offer “a faster route to approval for new treatments.”
The FDA already is saying “It may not be feasible to conduct pre-market trials that address all” the “theoretical risks in any reasonably sized study.” It says we won’t know whether some therapies work until we approve them, try them on people, see whatever consequences emerge and deal with those.
The test on the rhesus monkey involved AVXS-101, a gene treatment that has had success in helping infants up to nine months old by replacing the survival motor neuron 1 gene, which is missing or mutated in people with spinal muscular atrophy. The idea was to see what would happen if doses were increased to the point where older and bigger patients can receive it.
Perhaps, given the results, we should consider avoiding some of those accelerated approval pathways. Already, the FDA is struggling with recalls of blood pressure medication and other drugs, and in those cases, removing the drugs and replacing them with others tends to address the problem. In the case of gene therapy, we don’t even fully understand what causes the problems or how they might be avoided, and our ability to reverse any damage is limited by the nature of the treatment.
President Trump is right to push the gas pedal on childhood cancer and AIDS. Both seem within our medical and technology reach to eradicate. Both have seen recent progress in research that makes that promise even more tantalizing.
But our approval system already is under tremendous strain. There’s already a bottleneck in receiving and processing applications — as well as pressure to bring to market life-saving treatments for otherwise-deadly diseases as expeditiously as possible.
In a world that demands faster and faster, maybe it is time to go a little slower and get this right. Otherwise, we could be living with the consequences of failure for a long time.
• Brian McNicoll is a conservative columnist and freelance writer based in Alexandria, Va. He is a former senior writer for The Heritage Foundation and former director of communications for the House Committee on Oversight and Government Reform.