‘There’s so much uncertainty’: As Mallinckrodt sells rare disease drug, parents worry about access

As it looks to emerge from bankruptcy, Mallinckrodt (MNK) has sold an experimental medicine that until recently was being tested to treat a fatal genetic disorder. But the company has said it will work with the buyer to ensure it remains available to children, an unexpected twist in the latest controversy over access to a rare disease drug.

At issue is a medication called adrabetadex, which the company was studying to combat Niemann-Pick type C, or NPC, a rare progressive genetic disorder characterized by an inability of the body to transport cholesterol and other fatty substances inside of cells. The life expectancy of someone with the condition is about 20 years, but can be much shorter if NPC emerges during infancy.

Mallinckrodt, which obtained the drug as part of its $1.2 billion acquisition of Sucampo Pharmaceuticals in late 2017, ended clinical testing earlier this year after studies indicated the drug had no benefit. It was a devastating decision for families, because there is currently no treatment for NPC that has been approved for use in the U.S.


“After five treatments, my daughter started walking,” said Sara McGlocklin of Monrovia, Calif., whose five-year-old daughter, Marian, was diagnosed with NPC when she was a toddler and later had difficulty talking and walking. “Before treatment, it would take her six months to hit a new milestone. But after each treatment, she hit a new milestone. It was like a light switch turned on.”

After at least two possible buyers did not pan out, Mallinckrodt reached a deal on Wednesday to sell the drug to a little-known company called Mandos for $1 million and $2 million more in milestone payments, according to court documents. And Mallinckrodt agreed to secure enough supply to allow access to the drug for potentially up to two years under expanded access.


Expanded access, sometimes known as compassionate use, is a program overseen by the Food and Drug Administration in which a drug maker can agree to provide its medicine to patients with a life-threatening disease receive an experimental medicine, even though they are not enrolled in a clinical trial.

For the past several months, however, some families have attempted to gain access to the program for their children. But they’ve been turned away for reasons that in some cases have been unclear. The FDA and Mallinckrodt appeared to point fingers at one another over who is to blame for the obstacles, according to families and a Rush University Medical Center researcher in Chicago who has helped pilot the expanded access program.

“It’s been very hard to get to the truth,” said Elizabeth Berry-Kravis, a pediatrics and neurology professor at Rush, who has been in close contact with numerous families, as well as both agency and company officials. “The statements have been contradictory.”

“Mallinckrodt released a statement implying the FDA had required them to stop enrolling new patients as part of ending their development program,” she told me. “You have to read between the lines, though. But they’ve told me that was the situation. FDA has not officially said that’s the case. But in e-mails to me, (an FDA official) has said ‘No, I can’t allow it, it’s not an FDA program.’”

A spokesperson for Mallinckrodt maintained that it was a “mischaracterization” for anyone to suggest that the company was blaming the FDA. However, in an e-mail Mallinckrodt sent previously to researchers, the company acknowledged that, as part of its agreement with FDA to continue the expanded access program through October, it agreed “no new patients” would be able to start the drug.

Last week, however, Katie Donohue, the director of the Division of Rare Diseases and Medical Genetics — who Berry-Kravis said was the FDA official who would not allow additional children in the expanded access program  — changed her mind. In a note to one parent, she wrote that Mallinckrodt has final say. “We can’t force them to do that,” Donohue.

That note was sent to Denise Miller of Sun City West, Ariz., whose 22-month-old son, Woodrow, was recently prevented from enrolling in the expanded access program. Miller forwarded the note to Steve Romano, executive vice president and chief scientific officer at Mallinckrodt, who wrote back to say the company was “evaluating the situation and potential options, and hope(s) to reach a conclusion within the next few days.”

Miller family
Denise Miller and Rickey Miller with their son Woodrow Miller, who has Niemann-Pick type C. Courtesy Denise Miller

The sudden change of heart appears to reflect a few developments, including growing pressure on the FDA. Berry-Kravis and several other physicians who treat children with NPC, last month wrote a letter to Acting FDA Commissioner Janet Woodcock, urging her to accept new patients in the expanded access program. They cited studies indicating adrabetadex stabilized the disease over an extended period of time. In addition, several lawmakers recently began reaching out to the Department of Health and Human Services, as well as the FDA, to make the same push.

“Given the extreme urgency for (children) to receive this medicine, I am writing to ask you to use the many authorities and resources in your control to provide access… to this critical therapy and to act immediately,” Rep. Debbie Lesko (R-Ariz.), wrote to Woodcock on May 5. She also cited the same letter that was written by the physicians.

To an extent, the episode is reminiscent of earlier criticism of the FDA and its expanded access program, even though the agency has produced data showing more than 99% of requests are approved. The agency, in fact, is particularly sensitive about the issue after critics succeeded in getting the right-to-try law passed, even though drug makers remain gatekeepers for deciding who can access it medicines.

Patrizia Cavazzoni, the director of the Center for Drug Evaluation and Research, told us she could not comment on communications between specific individuals. But she did explain that the agency was keenly aware of the controversy surrounding adrabetadex and has remained “generally supportive” of some form of expanded access.

“From the center’s perspective, we’ve been working to find a path forward… under some form of expanded access. We’re still deliberating on this because we do recognize there may be some patients who may benefit,” she said. “This has been my position from the very onset of the discussion we’ve had… And we’re certainly open to it if the sponsor were to come and talk to us about doing more studies.”

To convince the FDA to approve the drug, though, will require additional clinical trials, and some say that can be problematic.

“The FDA has indicated (the company) would have to design a more complex study, a double blind, randomized control trial to obtain the data for approval,” said Marc Patterson, who heads the Division of Child and Adolescent Neurology at the Mayo Clinic. “The problem is in these ultra-rare diseases is that getting a trial that’s sufficiently powered is extraordinarily difficult. And is it really ethical when data suggests we have an agent that can prevent progression?”

Meanwhile, there was another development that appeared to break the logjam.

For the past year, Mallinckrodt had been exploring whether it could find a buyer for the drug. The company had filed for bankruptcy protection in response to mounting liabilities over lawsuits that accused it of contributing to the opioid crisis. Romano told parents earlier this year that the bankruptcy was not the reason trials were ended for adrabetadex, though.

Under the deal with Mandos, Mallinckrodt has agreed to secure enough doses to enable expanded access for up two years.

“Mallinckrodt as worked judiciously to identify an entity that would seek to find a path forward for the drug,” Romano said in a statement. “We are hopeful Mandos will further advance both the understanding of the disease and the potential to develop the drug as a future treatment option for NPC patients.”

Whether Mandos can achieve this goal is unclear.

The company issued a statement noting, that if the deal is approved by the bankruptcy court, it will continue the expanded access program and it will be overseen by Berry-Kravis. But there were no further details provided. Scott Riccio, who was identified in the release as the executive vice president for patient and community engagement, did not respond to an e-mail.

Riccio’s LinkedIn page notes he previously held similar positions at Myovant Sciences and Alder Pharmaceuticals, and that began working this month at “Stealth Biotech Startup.” Court documents, meanwhile, list Mandos as being headquartered on Sunset Boulevard in West Hollywood, Ca. A generic voice mail answers the phone number listed in court documents.

Interestingly, one of the Mallinckrodt creditors, Beren Therapeutics, is located at the same address — the same suite number, in fact — according to a filing with the California Secretary of State. And the Beren chief executive officer is listed as Jason Camm, whose LinkedIn page says he is managing director and chief medical officer at Thiel Capital, which is in the same building as both entities.

Thiel Capital is the investment run by Peter Thiel, a venture capitalist who co-founded PayPal and Palantir Technologies, among other companies. We left word for Camm and will update with you any reply.

The lack of insight into Mandos and its ability to develop adrabetadex and run an expanded access program has some parents concerned, although bankruptcy documents indicate Mallinckrodt will help run the program for three months after the deal closes, for a fee.

“It’s validating to know investors out there see the value in this drug, because I think the thing what’s been so frustrating for me as a mom. Our reality has never aligned with the narrative about the drug,” said Pam Andrews of Austin, Tex., who has two daughters suffering from NPC.

“But I don’t know if the company has the experience to work with the FDA to get them what they say they need. I’m scared for the kids. There’s zero room for error and there’s still so much uncertainty. It seems like a big mess.”

Source: STAT