FDA Tells Doctor to Stop Marketing Three-Parent Babies

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By Bronwyn Mixter

The FDA wants a fertility doctor to stop marketing three-parent babies.

The Food and Drug Administration told Dr. John Zhang in an Aug. 4 letter he should stop marketing an unapproved mitochondrial replacement technology, which combines the DNA of three people to create an embryo. The goal of the technology is to prevent mitochondrial disease, which can cause seizures, strokes, severe developmental delays, and other complications. The technique involves replacing small amounts of mitochondrial DNA in an embryo with DNA from a donor. Mitochondria are “organelles” within cells that provide chemical energy for cellular processes and contain small amounts of DNA.

In annual appropriations acts since December 2015, Congress prohibited the FDA from using funds to review applications related to genome-editing tools that modify the DNA of human embryos until safety and ethical issues can be resolved. Also, researchers don’t know what impact the procedure will have on the babies it produces.

FDA’s Hands Tied

University of Wisconsin bioethicist R. Alta Charo told Bloomberg BNA in an email she’s “pleased to see the FDA exercising its authority to protect American patients.”

“Indeed, I wish it would act more forcefully in other areas where far more patients are affected, such as in the realm of regenerative medicine, which is rife with misleading claims by clinics offering stem cell interventions that are neither approved nor under an investigational new drug (IND) application, Charo said. Researchers must first obtain the FDA’s approval of an IND before administering investigational drugs to humans.

But Charo said she finds “it frustrating that language in the federal budget’s continuing resolution has effectively tied FDA’s hands, making it impossible for the agency to properly review proposals for mitochondrial replacement.”

“By preventing FDA from doing its job, Congress has not protected patients. Instead, it has simply created incentives for practitioners and patients to look for ways around the regulations, thereby losing the valuable oversight FDA offers,” Charo said.

Charo said “it is important that this innovation be developed carefully, and with long-term follow-up to confirm the safety of the procedure for the children who are conceived this way. That is most likely to occur if the work proceeds within clinical trials overseen by a competent regulatory body.”

Marketing the Technology

Zhang, who is the chief executive officer of Darwin Life Inc., made a three-parent embryo in the U.S. and then exported it to Mexico for implantation, the letter said. He also submitted a written request to the FDA for a pre-IND meeting to discuss a clinical investigation of the technology, but that request was denied.

In the written request, Zhang said he wouldn’t use the technology in the U.S. until the FDA authorized a clinical trial, the FDA said. But despite that commitment he continued to market the technology to prevent the transmission of mitochondrial disease and to treat infertility, the agency said.

The FDA asked Zhang to respond to the letter and describe the steps he has taken or will take to address the issue. The letter was signed by Mary A. Malarkey, director of the Office of Compliance and Biologics Quality in the FDA’s Center for Biologics Evaluation and Research.

A spokesman for Darwin Life who asked not to be named told Bloomberg BNA Aug. 8 that the company “takes FDA’s letter seriously, and is in the process of clarifying the current status of our activities with FDA.”

“We are fully committed to complying with all applicable requirements, and look forward to helping patients in the future under the parameters established by FDA, COFEPRIS, and other health regulatory bodies,” the spokesman said. COFEPRIS refers to the Federal Commission for the Protection against Sanitary Risks, which regulates health issues in Mexico.

More Research Needed

George Q. Daley, a dean at Harvard Medical School and a past president of the International Society for Stem Cell Research (ISSCR), told Bloomberg BNA Aug. 8 he’s reassured that the FDA decided to take this action.

Guidelines from the ISSCR, the National Academy of Medicine, and the Human Fertilization and Embryology Authority in the United Kingdom “have called for far greater investments in research and preclinical evidence of safety before moving” to clinical use of the technology.

“And yet this practitioner, Dr. Zhang, went ahead and created an embryo and did the transfer in Mexico. So he clearly moved outside of the country in order to try to avoid the regulatory environment,” Daley said. “But the creation of the embryo was done in the U.S., which is a violation of the FDA’s oversight. And, according to my judgment based on the existing professional guidelines, this was a breach of professional ethics.”

Daley said whenever an embryo is being made “there’s significant amounts of manipulation and there’s significant concerns about the impact on the baby that’s born.”

“My hope, as a clinician who’s cared for patients with mitochondrial disease, is that this mitochondrial replacement strategy will ultimately prove safe and allow us to use the technology to enable families that are burdened by this disease to have natural born and healthy children,” Daley said. But even in the paper that Zhang published “he said the procedure did not eradicate the defective mitochondria and we don’t know what the impact of that is.”

Daley said there also have been babies born in China where the procedure hasn’t eradicated the defective mitochondria. “One could argue that these kids could be born with an improved outcome, but that hasn’t been proven,” he said.

To contact the reporter on this story: Bronwyn Mixter in Washington at bmixter@bna.com

To contact the editor responsible for this story: Randy Kubetin at RKubetin@bna.com

For More Information

The FDA's letter is at http://src.bna.com/rt6.

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