All the subsequent information gathered will be applied when they are ready for the next xenotransplant patient. That includes clues about how to prevent issues that may have contributed to the heart failure, including a reaction to a drug aimed at preventing rejection.
“We are still trying to figure out what went wrong; we don’t have a single answer,” said Muhammad M. Mohiuddin, co-leader of the pig heart study and professor of surgery and scientific/program director of the cardiac xenotransplantation program in the medical school.
“But we don’t consider this a setback,” he said. “We consider that he lived through the surgery the first win. When he seemed to be recovering and doing well for two months, we really thought that was a huge success. If we could have identified the reason his heart gave out suddenly, he might have walked out of the hospital.”
An autopsy found Bennett’s body didn’t show traditional signs of rejecting the heart. Rather, doctors found a thickening and then stiffening of the heart muscle, perhaps a reaction to a drug used to prevent rejection and infection. That made it unable to relax and fill with blood as it’s supposed to.
According to the doctors’ study, which was published in June in the New England Journal of Medicine, they also found DNA from a latent infection in the specially reared pig that evaded precautions and screening. It’s still not clear whether that contributed to the heart failure.
Bennet, 57, had been bedridden and hooked up to a lifesaving heart-lung bypass machine for eight weeks with end-stage heart failure before the transplant with the genetically modified pig heart. He was not eligible for a traditional heart transplant and federal regulators granted him a “compassionate use” exemption to have the experimental pig-heart transplant. Such animal organ transplants are not approved by the Food and Drug Administration.
For now, any more such transplants will be considered on a “case by case basis,” according to a statement by a FDA spokesperson to the Baltimore Sun.
The agency wouldn’t comment on if and when regulators would allow human trials, which typically mean larger numbers of transplant patients, multiple hospital sites and data collection with the goal of approval for the procedure. The Wall Street Journal, citing “sources familiar with the matter,” reported last week that the FDA was devising such plans.
FDA officials acknowledged to the Sun a need to address the shortage of organs for transplant.
“Xenotransplantation represents an option to help address the shortage of human allografts and organs for transplantation,” according to an FDA spokesperson.
But the FDA also cited the complexity and risk from animal transplants, including transfer of infections, and the need to “carefully assess” those risks compared with the potential benefits in any trial.
“Overall, FDA will not allow an investigational product to be used unless it believes that such risks are appropriately minimized and acceptable for the clinical situation,” the spokesperson said. “Because of the potentially serious public health risks of possible zoonotic infections, FDA has instituted policies such as long-term patient monitoring and prohibitions against blood donation to mitigate against the risk of infectious-disease transmission.”
Mohiuddin said doctors have been in touch with the FDA about human trials but said there would be more animal studies in the meantime.
“I think the presentations made to the FDA by those in the field indicate that the best path forward is through a human clinical trial,” he said. “We are eager to see how the FDA responds to this input and whether they will issue new guidance on this. As of now, we are proceeding with additional primate studies to see what more we can learn.”
But Mohiuddin said doctors already know the findings from Bennett’s transplant will lead to changes to practices and techniques in future human transplants.
Patients and their families have been contacting him and other doctors since the transplant was announced, but there is no timeline to request approval for another transplant.
“There is a patient population that could benefit from this, and many have offered, volunteered for the procedure,” he said. “Before we satisfy anyone else, we have to be satisfied what we have learned can be applied to the next one.”
The transplant was the result of a $15.7 million research grant from the Virginia-based biotech company Revivicor to study its genetically modified pig UHearts in baboons.
About 110,000 Americans are waiting for an organ transplant, with more than 6,000 dying annually while they’re on the list, according to federal figures.