Clinical trial of Retrophin drug fails; Shows no benefit for PKAN patients
A much-anticipated drug therapy has failed to show any benefit for individuals affected with PKAN, or Pantothenate Kinase-Associated Neurodegeneration, one of the most common forms of NBIA.
The drug’s maker, Retrophin Inc., announced the disappointing results Aug. 22 for its Phase 3 Fosmetpantotenate Replacement Therapy, or FORT, study.
Seventy-eight PKAN individuals had completed the 24-week randomized, double-blind study, meaning that neither the patients nor the doctors knew who was randomly selected to get the drug or the placebo. At the end of the study, 76 patients decided to participate in the open-label program in which all received the drug.
Although the drug, Fosmetpantotenate, was observed to be generally safe and well-tolerated, the study found that it did not meet its primary or secondary endpoints, or outcome measures.
First, the study found no differences between those who received the drug and those who got the placebo. That determination was based on the extent to which individuals improved over the 24-week trial, based on a scale that measures activities of daily living, such as walking, eating and dressing. Those measures were specifically adapted for PKAN individuals using Part II of the comprehensive and widely referenced Unified Parkinson’s Disease Rating Scale.
Second, the study found no measurable change on the same scale’s Part III score, which evaluates motor function, including slowness, stiffness and balance.
No data suggested that a longer course of treatment would change the outcomes, nor were any differences seen between classic and later-onset PKAN individuals taking part in the trial.
“We are very disappointed in the topline results from the FORT Study, particularly because we have seen the devastating impact of PKAN on patients and their families, and a significant unmet need remains with no approved treatment option,” said Retrophin CEO Eric Dube, Ph.D. "We would like to thank the patients, their caregivers, study investigators and our employees, whose dedication made this study possible.”
The study gathered a significant amount of data, which is still being analyzed. Retrophin plans to present its findings at scientific meetings in the fall. It also will publish the findings in a peer-reviewed journal. Company officials said they hope the data will help inform future clinical studies for treating PKAN.
Deferiprone trial results produce positive findings for some with PKAN
The long-awaited results from the first international clinical trial for NBIA — testing deferiprone in individuals with PKAN — are in.
They show that the iron-chelating drug slowed the progression of the disorder in older patients with a later-onset, or atypical, form of PKAN, but did not have a similar benefit for younger patients with classic PKAN, which starts in early childhood.
In addition to those findings, the study showed that the drug successfully reduced the amount of accumulated iron in the brain for PKAN individuals, regardless of onset age.
PKAN, or Pantothenate Kinase-Associated Neurodegeneration, and all other NBIA disorders share iron accumulation in the globus pallidus structure of the brain. It remains unclear, however, whether excess iron causes NBIA or is brought on by some other problem.
The results of the trial, which was funded by a European Union grant titled Treat Iron-Related Childhood-Onset Neurodegeneration, or TIRCON, were presented at the Tenth International NBIA Family Conference held May 30 to June 2 in Charleston, S.C. The findings were then published in the July issue of the medical journal, Lancet Neurology.
The lead investigator of the trial in the United States, Dr. Elliott Vichinsky of the University of California, San Francisco Benioff Children’s Hospital in Oakland, discussed the results at the conference. He said that older and younger PKAN individuals showed improvement with deferiprone in dystonia of the lower face and lower legs, as well as in cognitive functioning, especially memory. But the benefit in the younger children, who tend to have a faster-moving, more severe form of PKAN, “wasn’t statistically significant,” he said.
The 18-month trial, which ran from 2012 to 2015, involved 88 patients from the United States, Germany, Italy and England. The trial met the gold standard for research. It was randomized, with some patients getting deferiprone orally and others getting a placebo. Afterward, the trial was extended another 18 months, and the drug was made available to everyone who took part in the trial.
“The drug was well-tolerated, and the safety profile was very good,” Vichinsky told families at the conference.
But because the study did not meet a key goal — showing a statistically important improvement from deferiprone in all age groups — the U.S. Food and Drug Administration hasn’t yet approved it for PKAN. Consequently, Vichinsky encouraged interested families to contact the FDA to advocate for its approval.
To read the full article:
To see his presentation, go to the YouTube channel for the NBIA Disorders Association conference here: