FDA advisory panel rejects drug-device combination to treat Type 2 diabetes

A Cambridge biotech had challenged earlier FDA rejections in an unusual appeal

The Food and Drug Administration building in Silver Spring, Md. A panel of medical advisers on Thursday unanimously dashed a Cambridge biotech’s hopes that US regulators would reconsider a twice-rejected implantable device designed for adults with uncontrolled blood sugar stemming from Type 2 diabetes.SARAHBETH MANEY/NYT

A panel of medical advisers on Thursday unanimously dashed a Cambridge biotech’s hopes that US regulators would reconsider a twice-rejected implantable device designed for adults with uncontrolled blood sugar stemming from Type 2 diabetes.

In a 19-0 vote, the panel concluded the device’s benefits were outweighed by its safety risks, including the potential for kidney and heart problems. The vote essentially upheld the Food and Drug Administration’s earlier rejections, although some members called for new clinical studies to address safety and dosing concerns.

The device, called ITCA 650, is inserted under the skin and releases the drug exenatide continuously for six months, making it easier for diabetics who don’t take other medicines as prescribed. Some 30 million Americans suffer from Type 2 diabetes.

About a dozen diabetes patients and doctors, including some who ran clinical trials around the country, told the advisory panel that the drug-device combination led to beneficial weight losses and lower blood sugar levels in patients, who preferred it to injections or pills.

But an FDA staff review of the clinical data showed the risk of acute kidney injuries and major adverse cardiac events such as heart attacks or strokes in patients, along with troubling inconsistencies in the amount of drug the device released over time.

“The sliver of benefit is awfully thin to counterbalance what we don’t know and what signals we are seeing with respect to [safety] risk,” said committee member Dr. Brendan Everett, a cardiovascular medicine specialist at Brigham & Women’s Hospital in Boston.

The panel was convened by the FDA’s chief scientist, Dr. Namandjé N. Bumpus, for a rare hearing to address objections raised in an appeal by i2o Therapeutics — which acquired the device and drug combination this year — of previous decisions. The FDA’s Center for Drug Evaluation and Research rejected the product in 2017 and 2020.

A detailed point-by-point rebuttal of earlier findings was led by i2o chief executive Kurt Graves. Graves spent more than a decade trying to win approval of the diabetes treatment when he led Boston-based Intarcia Therapeutics. In 2020, after the FDA rejections, Intarcia auctioned off the device technology, which was acquired by i2o.

Graves and other i2o representatives argued that many of the safety risks found in clinical trials were common to, and no worse than, those in approved Type 2 diabetes medications. Those risks could be reduced in part by making sure patients are well hydrated, i2o officials said.

Most of the speakers at a public forum that was part of Thursday’s hearings said the device should be allowed on the market, arguing it was easier than frequent injections or oral medications and helpful to a large share of patients with Type 2 diabetes.

“Let’s keep moving the innovation and get it to market,” said Kelly Close, founder of Close Concerns, a San Francisco health information firm focusing on diabetes and obesity.

Dr. Lisa Connery, a family medicine physician in Norman, Okla., who implanted the matchstick-sized devices in patients during a four-year clinical trial, told the committee, “They are very well tolerated.”

She said one patient, an oil patch worker, couldn’t take other medicines regularly because of long hours in the field but experienced a big drop in his blood sugar levels with the ITCA 650 device. “Even after he moved from Oklahoma to Texas,” she said, “he chose to come back every six months to get the implants done because it was life-changing for this gentleman.”

Advisory committee members, even while turning thumbs down on the treatment, didn’t dispute its benefits. They said a subcutaneous implant could be helpful if the safety concerns could be mitigated.

“There is compelling reason to carefully consider this drug-device combination,” said Dr. Rita Kalyani, a committee member who is an associate professor at Johns Hopkins University School of Medicine. “The question is whether there’s adequate data to demonstrate that everyone who wants to take it could take it in a safe way.”

Everett, of Brigham and Women’s, said he had “serious concerns” about acute kidney disease seen in a small number of clinical trial patients, especially because the trials likely enrolled fewer patients with chronic kidney disease than in the broader diabetic population.

“I worry that if the drug were used in a non-clinical trial population, the rates of acute kidney disease would actually be higher,” he said.

An earlier version of this story misstated how Intarcia ended its operations in 2020.