Update on the CoA-Z clinical trial
Over the past several months, the OHSU CoA-Z study team has shared the initial study results with all CoA-Z study participants and their families, as well as the broader NBIA community of families, friends, clinical providers and supporters. The following is a translation of an announcement by Penny Hogarth and the OHSU CoA-Z study team from NBIAcure's November newsletter: https://nbiacure.org/wp-content/uploads/2023/11/NBIAcure-Newsletter-November-2023.pdf
We had already recognized (from previous studies in PKAN mice and human samples) that 4′-phosphopanthezine ("CoA-Z") bypasses the genetic "roadblock" in vitamin B5 metabolism in PKAN. This suggests that CoA-Z will alter disease progression over time. However, measuring a real change in disease progression in PKAN (or any other neurological disease) usually takes many years, so the overall aims of the clinical trial were limited to finding out whether CoA-Z causes any health problems or side effects and whether it changes a particular blood level that we think is a good biomarker of the disease. It is important to remember that the clinical trial was not designed to measure a change in PKAN symptoms, at least not in a way that we could measure in the trial.
So far, our work has focused on analyzing individual participant data from the first six months of the study. This was the 'double-blind' phase, where participants were randomized to receive either a placebo or one of three different doses of CoA-Z, without us knowing which group a participant belonged to. This is the best way to determine whether the differences we find are due to CoA-Z itself or are just due to chance. We are very encouraged by some of the overall results of the project:
So far, we have not noticed any major health problems or side effects of CoA-Z during the study.
Perhaps most encouragingly, we see a pattern in the biomarker results that strongly suggests that CoA-Z alters an important biological measure of disease, just as we predicted. And we found that this response was dose-dependent, meaning that higher doses tended to lead to a greater change in the biomarker.
In some ways, the biomarker results are most important because they confirm that CoA-Z acts on the central vitamin B5 processing problem in PKAN, just as we predicted. These results give us real hope that the drug will slow the progression of PKAN, although we still need to figure out the best dose and how early in life to start treatment.
At the NBIA Family Meeting in May and in our follow-up communications to CoA-Z trial participants, we mentioned the possibility of conducting one or more short follow-up studies with CoA-Z to supplement our clinical trial data. After further data analysis and consideration, we have concluded that our current data is meaningful enough to submit to the FDA without additional clinical trials. If approved by the FDA, this is the fastest path to the approvals we need to make the drug more widely available to the PKAN community.
So we are putting aside all plans for follow-up studies for the time being and instead focusing entirely on compiling our data to submit to the FDA. This is a big task, because it's not just the data from the CoA-Z clinical trial, but also all the related background work going back to 2015: more than 500 pages! We don't have the resources to make CoA-Z more widely available before FDA approval, so we think this is the best way to make it widely available to the PKAN community.
We know that everyone feels the urgency to make CoA-Z available. We feel it too. We also know that the community is very interested in our progress and we will continue to keep you informed. We are delighted to be at this point and are very grateful to the PKAN community and all our supporters for their contributions to the CoA-Z study so far.
Translation of an announcement by Penny Hogarth and the OHSU CoA-Z study team, IRB study 18782 from the November NBIAcure newsletter:
https://nbiacure.org/wp-content/uploads/2023/11/NBIAcure-Newsletter-November-2023.pdf
