NPC community seeing a burst of hope—and concern—as treatment for rare disease moves into new hands

NPC community seeing a burst of hope—and concern—as treatment for rare disease moves into new hands

When Daily Kos first covered the situation with children suffering from Niemann-Pick type C (NPC) and the possible treatment now called adrabetadex back on April 14, the story was left at a moment of confusion, frustration, and real fear that the only available treatment for this heartbreaking disease was about to become unavailable. Since then, the incredible community of parents, patients, and doctors has weathered another painful setback, won a key individual victory, and been given a signal of real hope ahead.

When massive pharmaceutical company Mallinckrodt had filed for Chapter 11 bankruptcy in October 2020, it was entangled in a series of legal setbacks involving potentially billions of dollars in settlements related to opioids, and a massive fine from the FDA involving an illegal monopoly on a drug used to treat another rare childhood disease. Against that background, the company announced that it was ending the Phase 3 trial of adrabetadex, reporting that they could find no net positive results when comparing the patients getting active treatment with those getting placebo.

That disappointing ending came at the end of many years of apparent progress, years in which adrabetadex had appeared to be highly effective both in animal trials and in initial trials with volunteers. The National Institutes of Health had spearheaded research behind the drug and helped set up a startup company that existed solely to move the treatment forward through years of trial. But when that company was then bought out and changed hands twice before the company and the drug ended up as parts of Mallinckrodt, the abrupt end of the trial caught families by surprise. For many, they were left looking at a countdown to the day when the treatment they believed was helping their child would no longer be available. For others that countdown was much shorter—some facilities refused to continue giving treatment that was no longer part of an ongoing trial.

For every NPC patient and parent, it seemed that hope had taken a giant kick in the face. Adrabetadex was never considered a cure, but it was hoped that it would slow the course of the illness until a potential cure could be found. With Mallinckrodt withdrawing from the trial, that chance appeared to be over.

But in the last four weeks, a lot has changed.

NPC is a very rare childhood disease that involves an inability to transport cholesterol and lipids inside cells. Over time, these substances pile up in the tissues of many organs, including the brain, and cause progressive damage. The disease is caused by a very rare recessive gene and can strike at any age, but with younger patients the disease is invariably fatal. The horrible progression of the disease in children can be seen in its ghastly nickname: “Childhood Alzheimer’s.” About 40 children a year are diagnosed with this illness in the United States.

Adrabetadex is a form of cyclodextrin, part of the family of complex sugars known as oligosaccharides. Cyclodextrins have often been used as delivery agents for other drugs, and the particular form that would become adrabetadex was discovered when it was used as a delivery agent in a trial for another drug. The first tests of adrabetadex were so compelling that not only did the National Institutes of Health (NIH) help move the drug toward human trials, a number of families were granted almost immediate permission to begin treatment as part of an extended compassionate use program that is still ongoing.

Despite being hailed as a “breakthrough drug” and racking up considerable anecdotal evidence of improvement from both families and doctors, further production of adrabetadex was halted after Mallinckrodt delivered a heartbreaking letter to families saying: “Effective immediately, Mallinckrodt is recommending that treatment with adrabetadex be discontinued as soon as possible …” The trial and the compassionate use program were both to be brought to a close, and the remaining doses of the drug were set to be gone by September.

The history of the drug, the human trials, and the incredible hurdles faced by the NPC children and their families were covered in Part I and Part II of a lengthy article in April. 

Johnson & Johnson

One hope among the NPC community was that Johnson & Johnson might take up the manufacture and distribution of adrabetadex. Johnson & Johnson had manufactured the cyclodextrin originally used in the NIH trials, and continues to manufacture similar compounds for their original use as delivery agents. What’s more, a handful of patients—those from the earliest days of the compassionate use program—had always received their treatment from Johnson & Johnson.

But shortly after the publication of that first article, Johnson & Johnson made it clear this wasn’t going to happen. Though the company would allow those still in their extended care program to continue treatment, they would not accept any new patients. 

Considering the complexity of dealing with a drug that was officially owned by another pharmaceutical company that had initially paid over $1 billion for a company that had its entire value boiled down to its rights to adrabetadex, this wasn’t surprising. However, it did mean that several patients were shut out of any possible treatment.

That included recently diagnosed 21-month-old boy named Woodrow Miller.

Woodrow

But Woodrow’s story, relayed in an open letter to the NPC community from the parents who have come together to create Don’t Give Up on NPC, turned into an important victory for Woodrow, his mother Denise Miller, and for all the NPC parents. 

Woodrow Miller with Emma Peterka, who was featured in the earlier articles.

Multiple NPC parents directly approached their members of Congress and, demonstrating that this can be effective even in these anything-but-bipartisan times, the family and friends of Woodrow eventually generated a letter from the unlikely trio of Sen. Kyrsten Sinema, Sen. Mark Kelly, and Republican Rep. Debbie Lesko. Lesko even created a video directed at new Health and Human Services Secretary Xavier Becerra.

The result of all this effort on the part of Woodrow’s mom and the extended NPC community is that Woodrow Miller is now the first person to be added to the extended use program since Mallinckrodt pulled the plug. He has started treatment with Dr. Elizabeth Berry-Kravis at Rush University Medical Center, who the parents have described as “a bedrock of optimism and care.”

But there’s another factor that made Woodrow’s admission into the program possible, and that’s the factor that generates the most hope—and the greatest concern—among the community. Because if all goes well, adrabetadex will soon no longer belong to Mallinckrodt.

Mandos

As Businesswire reported on May 19, Mandos has entered into an agreement to acquire adrabetadex. And the way in which that announcement has been worded generated a huge burst of excitement.

This acquisition, if approved, will allow Mandos to pursue both the continuation of the U.S. Expanded Access Program under Rush University Medical Center (RUMC) and future research and development of adrabetadex for patients living with NPC1. 

The possible continuation of the expanded access program would be an enormous relief to the parents of young children facing NPC at this moment. That’s especially true if, as in Woodrow’s case, it means more patients can be enrolled.

But the bigger implication here is that Mandos intends to resume the trial of adrabetadex. In conversations with the parents and other, Mallinckrodt researchers have admitted that the original phase 3 trial was flawed in several ways. Not least of all, it was simply too short to determine if adrabetadex is effective in slowing or halting a disease with a progress that can be difficult to measure over a period of months. Mallinckrodt’s chief scientific officer suggested that an effective trial of adrabetadex would require something close to three years.

Under the announced agreement, Mallinckrodt will transfer its sponsorship of an investigational new drug application with the FDA to Mandos. Mallinckrodt will then assist Mandos in closing the existing clinical trial and transitioning all current trial patients to the expanded access program. All of this is subject to approval of the U.S. Bankruptcy Court for the District of Delaware, as it’s still taking place under Mallinckrodt’s Chapter 11 reorganization. 

But while both Mallinckrodt’s and Mandos’ statements concerning the transfer contain hopeful language about “advancing the understanding” of NPC and the future potential of adrabetadex, there doesn’t seem to be a definite commitment to resume a new trial and seek full FDA approval of adrabetadex over the long term. And that needs to happen.

Because NPC patients and their families don’t just deserve access to treatment, they deserve to know if that treatment is genuinely effective. At the moment, despite the early promise and the confusing nature of Mallinckrodt’s withdrawal, the efficacy of adrabetadex is unknown. There is a lot of hope hanging on this drug, and everyone involved needs to know that hope is earned.

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