Recruitment is not going well for PRIDE-HD, an important clinical trial now enrolling for Huntington's disease (HD). Why is this? Some think "why bother", particularly when testing a drug they may perceive as a failure in earlier trials. For some others, the trials may seem to too hard, too long, or not permit other drugs they are taking. Still others are waiting for the gene therapy magic bullet they believe is just around the corner.

Maybe we should look a little deeper?

Is pridopidine a failed drug? Two earlier trials of pridopidine did not show enough improvement in the chosen endpoint, a change in a subset of motor symptoms, for drug approval. However both trials showed meaningful benefit when change in all motor symptoms was considered. The motor symptoms that improved relate to hand coordination and walking ability, very important symptoms indeed. Dr. Ralf Reilman, a recognized expert in HD motor symptoms analyzed the results of the two trials and found that "the cummulative evidence for a positive biological effect of pridopidine on motor symptoms in HD is very strong and convincing" [Reilmann R 2013].

Further, in the earlier studies the doses of the drug used did not have side effects any greater than placebo. The PRIDE study will test higher doses with the expectation that higher doses will give even greater benefit. Of course, investigators will be looking carefully for greater side effects too.

Is this trial too long, too hard or limit use of other drugs?

Long and Hard: This trial takes a year. And it is hard, with some of the visits lasting the better part of a day, and some of those requiring a partner. The earlier trials that were not quite good enough were 3 and 6 months long. The longer trial will more likely give us a definite answer. And there are a lot of different assessments including fancy new instruments to measure motor function that improve measurements, but add to the length of the day.

And some good news: at the end of the trial, if no safety issues, all participants will be able to stay on the drug, allowing participants to have the drug before FDA process is completed.

Excluded drugs: Drugs like tetrabenazine, some antidepressants and certain antipychotics are not allowed. These drugs are excluded for several reasons that include those that could interfere with measuring results (like tetrabenazine), and drug combination safety (like certain antidepressants antipsychotics). For some individuals it is often possible to switch to another similar antidepressant or antipsychotic drug that would be allowed in this trial.

Should we wait for the gene therapy cure? First, in spite of the hype and hope promoting these therapies, the experts agree this is still years away from more than first safety trials. It isn't a good reason for not participating in this or other present trials that require a 1 year time. And next, the experts also agree that gene therapy as now proposed -- even if it works -- will not be the cure. Barring a miracle, it will be only a part of best treatment for HD. We will need other drugs too.

Author's comments: No question, PRIDE is a lot of work for participants and families. But, I believe there are very good reasons to expect this trial will succeed and bring HD patients a helpful drug. And it's not just me: some very smart HD experts like Dr. Michael Hayden now at TEVA Pharmaceuticals and Dr. Ralf Reilman who is a lead coordinator of this trial think so too.

The bottom line is that finding new drugs for HD takes a lot of work, good trials and a long-term commitments from HD families and investigators. If we don't join this or other trials, we will never have new drugs for HD: not for ourselves or the next generation. So if you fit criteria, I encourage you to go sign up for this very important trial, and whether you can join or not, encourage others.

References

Reilmann R. The pridopidine paradox in Huntington's disease. Mov Disord. 2013 Sep;28(10):1321-4. doi: 10.1002/mds.25559. Epub 2013 Jul 11. PubMed abstract