Well, the trial was in patients with early Huntington’s disease (HD). This was a long trial, 78 weeks, and it included patients on all concomitant medications. Patients had some entry criteria that were fairly standard, and they were classified by a total functional capacity greater than 7, which indicated early HD: stage I and II in HD terms. There already was some knowledge that certain neuroleptics and anti-chorea drugs could undermine and impair the results...
Well, the trial was in patients with early Huntington’s disease (HD). This was a long trial, 78 weeks, and it included patients on all concomitant medications. Patients had some entry criteria that were fairly standard, and they were classified by a total functional capacity greater than 7, which indicated early HD: stage I and II in HD terms. There already was some knowledge that certain neuroleptics and anti-chorea drugs could undermine and impair the results. We then looked, and the endpoint was the total functional capacity (TFC). The most important secondary endpoint was cUHDRS. This measures four components that contribute to progression in HD. These include: total functional capacity (made of five domain measures; finance, what you’re doing, activities of daily living, who cares for you, and employment), cognition (measured by Stroop word and SDMT), and motor function measured by TMS.
In the whole population, the results did not reach significance for a primary endpoint. But, we pre-specified looking at patients off ADMs (antidopaminergic medications) because we knew these may have an impact on our drug. Our drug is a CYP2D6 inhibitor. These ADMs are metabolized by CYP2D6, so in the presence of our drug, you would expect to see higher levels with the appropriate side effects of sedation, somnolence, or difficulty in concentration. These patients are even told not to drive. These are the functional endpoints that we’re measuring in this trial. When we looked at this particular group, we saw significant benefits. We saw benefits on total functional capacity all the way out to 78 weeks. We also saw, surprisingly, improvement from baseline. Huntington’s disease is a progressive disease, which escalates for every endpoint. It’s ultimately progressive for everything. Here, we saw improvements from baseline up to 52 weeks, and then for every measure thereafter. Consistently, the results were better than placebo.
We also measured Q-Motor, which is a measure of fine motor coordination. This showed significance all the way out to 78 weeks and never went below baseline. Stroop word measurement also showed improvement from baseline significant up to 52 weeks, and never went below baseline. So, these patients’ quality of life was preserved. All in all, for the first time in this disease, there’s a drug that showed a slowing of progression or improvement in function from baseline in patients. We were pleased to see that we saw positive effects in patients off antidopaminergic medications (neuroleptics taken often for behavior and anti-chorea medications taken for managing chorea). We also saw preservation of quality of life.
We then went back to 4 prior studies that had also done this, but had never looked at it without ADM. We did an independent integrated efficacy analysis, which I’ll be presenting today to the AAN. This showed significant benefits now in TFC, with greater power due to greater numbers, and also in cUHDRs progression, particularly in Stroop, and in Q-motor, all of which then replicated and provided consistency with the prior study.
In Huntington’s disease, we’ve had discussions with the European regulators that have given us a support to submit a marketing authorization for approval in Europe. This will have to go through the whole process, and we will be submitting that sometime in the next few months, aiming for marketing authorization. Another important point for this drug is complete safety. There are no serious adverse events with 1500 patients-years. This is a drug where the risk-benefit is in favor of benefit. We hope to convince the regulators to approve this, for approval in Europe in 2025. We are still having discussions with the FDA (the US regulators), and we’re waiting their response and working with the FDA to define the path forward for pridopidine in the USA.
