Orphan Drug Recall Leaves Patients in the Lurch

Regulatory NewsRegulatory News | 11 November 2019 |  By 

When Brenda Shelton, a hair stylist in Las Vegas, logged into a private Facebook group in September, she did not expect to find out about a recall of an injectable drug she takes to control her hypoparathyroidism, a rare disorder with potentially deadly complications.

And since Takeda’s Natpara (parathyroid hormone) injection is the only effective treatment for Shelton, she knew when she received an official Takeda recall letter via UPS four days later that difficulties were coming.

“I took my last injection on October 29, and have since been taking Calcitriol and calcium supplements (20 per day) with no other alternative,” Shelton told Focus via email. “The transition has been extremely difficult.” According to the Mayo Clinic, low levels of the parathyroid hormone lead to abnormally low calcium levels in the blood and bones, which can lead to impaired kidney function or heart failure.

At least 100 people with hypoparathyroidism have been hospitalized since the recall was announced, according to estimates from patients and surveys from Facebook groups. A Takeda spokesperson, who confirmed there have been hospitalizations, added: "We have no way of tracking all hospitalizations that may potentially occur as a result of hypoparathyroidism patients coming off of NATPARA treatment."

Shelton explained that at times she has problems breathing and swallowing, and the cramps in her hands and arms can force her to take leave from work, which reduces her income. She said she did not qualify for a program offered by Takeda, known as the Special Use program, which allows a limited number of patients to access Natpara while the recall is ongoing.

“It’s difficult on my family, as well, as they are worried about the symptoms becoming more severe. There have been a few days since discontinuing Natpara, that I should’ve gone to the hospital, but I refuse to do that because the physicians there do not understand this rare disease,” Shelton said.

Heather Novak, an author in Detroit, also began relying on Natpara after a parathyroidectomy when she was 18. But Novak was one of the “few lucky ones,” she told Focus, because she was accepted into Takeda’s Special Use program following the recall.

“Special Use is a lifesaver, but it comes with its own set of stress (albeit way less stress than being without Natpara). They only ship out seven vials at a time, we ship them back for inspection, and our compliance with the program is reviewed every 28 days. Late shipments, Takeda staff meetings, and pharmacy issues cause continuous problems,” Novak wrote to Focus via email. “Some people have missed doses because of shipping errors. Missing doses is life-threatening.” 

She said she thinks Takeda and FDA “had no idea what they were getting into” when they announced the recalls. “Even with stable calcium, patients who have discontinued the medication are saying the bone and muscle pain is nearly unbearable. Many people are fighting to save their kidneys and are worried about having cardiac episodes due to their history,” Novak added.

Since the US Food and Drug Administration (FDA) announced the Natpara recall was Class I last month, due to a manufacturing issue where small rubber fragments may detach into the injection, both Shelton and Novak said they have not received any updates from Takeda or FDA on when their medications will be available again.

“The fact that it's been two months and we've heard nothing is unacceptable,” Novak said. Shelton also said her endocrinologist never received the initial recall letter from Takeda. Takeda’s handling of the recall and the Special Use program is unethical, Shelton noted.

Arthur Caplan, head of the division of medical ethics at New York University’s School of Medicine, told Focus via email: “Those making orphan drugs ethically need to create a program to allow patients time to wean off a drug. The manufacturer should try to build a reserve to permit this before telling patients to go cold turkey. Legally can they get away with abandonment? I think so. Morally, not a sliver of a chance, especially when there are no other options and if they have been enjoying profits for some time due to orphan status.”

Shelton and Novak are not alone as there are about 2,700 patients on Natpara in the US, according to Takeda. 

A Takeda spokesperson added: "We are working closely with the FDA to resume supply as quickly as possible. We are in regular discussions with the FDA, and we have submitted short- and longer-term proposals for bringing NATPARA back to the market. But, at this time, we can’t predict a timeline because it’s unknown."

More patients have also been added to the Special Use program in the meantime.

"The Special Use Program, which was originally intended to be for an extremely limited number of patients (estimated around 30), is now up over 200. This is due to the high number of complex cases and individual disease parameters that qualifies them for the program given the parameters we set with FDA," a Takeda spokesperson said. 

Those outside FDA, the hypoparathyroidism community and Takeda are beginning to take note. Three Vermont lawmakers, including presidential hopeful Bernie Sanders, sent a letter to FDA last month seeking more information about the recall and what’s being done.

FDA, meanwhile, referred Focus to its drug shortage page for Natpara, which was last re-verified without an update on 23 October.

And Natpara is just one example of a growing list of drugs that are in shortage because of a manufacturing problem. Less than two weeks ago, FDA released a drug shortage report revealing how 62% of drug shortages between 2013 and 2017 were due to quality issues.


© 2022 Regulatory Affairs Professionals Society.

Discover more of what matters to you

No taxonomy