Deferiprone was well-tolerated, safe, and appears to slow disease progression in pantothenate kinase-associated neurodegeneration (PKAN), according to research published in The Lancet.
In this 18-month, randomized, double-blind, placebo-controlled trial, investigators followed a pre-planned 18-month open-label extension study that included patients with PKAN (n=88). Using a centralized computer random number generator and with stratification based on age group at the onset of symptoms, patients were randomly assigned to the deferiprone group (n=58) or placebo group (n=30). Patients had no evidence of iron deficiency, neutropenia, or abnormal hepatic or renal function. The two primary end points were the change from baseline to month 18 in the total Barry-Albright Dystonia (BAD) score and the Patient Global Impression of Improvement (PGI-I) scale score after 18 months.
For patients in the deferiprone group, BAD score worsened by a mean of 2.48 points after 18 months, as opposed to a change of 3.99 points for patients in the control group (difference -1.51 points; 95% CI, -3.19-0.16; P =.076). Patients continuing deferiprone in the extension study retained a similar rate of disease progression, with a change of 1.9 points) in the first 18 months vs 1.4 points in the second 18 months on the BAD scale, (P =.268).
Patients switching from placebo to deferiprone seemed to demonstrate slowing progression (4.4 points vs 1.4 points; P =.021). No subjective change was observed between groups based on PGI-I scale scores. Likewise, patients did not detect changes in the subsequent 18 months of treatment as mean PGI-I scale scores for the deferiprone to deferiprone group was 4.1 vs 4.7 for the placebo to deferiprone group. Aside from a larger occurrence of anemia in the deferiprone group, adverse events were similar between the deferiprone group and control group, and deferiprone was well tolerated.
The major limitation of this study is the lack of adequate pre-existing natural history data to enable an informed power calculation for the primary outcome related to change in the BAD score.
Study researchers concluded that these findings are the first to indicate a decrease in disease progression in patients with neurodegeneration with brain iron accumulation. Further, the researchers stated that the “extensive information collected and long follow-up of patients in the trial will improve the definition of appropriate endpoints, increase the understanding of the natural history, and thus help to shape the design of future trials in this ultra-orphan disease.”
The study was partially funded by ApoPharma, Inc. Several authors acknowledge conflicts of interest. Please see reference for the full list of disclosures.
Klopstock T, Tricta F, Neumayr L, et al. Safety and efficacy of deferiprone for pantothenate kinase-associated neurodegeneration: a randomised, double-blind, controlled trial and an open-label extension study. The Lancet. 2019;18(7):631-642.