The results of the PROOF-HD study in Huntington's disease are not as expected

Pridopidine has a long history. The drug was initially tested by the NeuroSearch company which believed that it had an effect on dopamine as its main mechanism and was therefore able to act on movement coordination. On this assumption, starting from 2007, two studies were conducted, MermaiHD and HART, both failed.

In 2012, Teva Pharmaceuticals bought the right to test pridopidine again and promoted a third study, PRIDE-HD, which tested different doses, again with the aim of verifying the drug's effects on motor function.

The PRIDE-HD study ended in 2016 with a negative result and a very strong placebo effect. However, this trial has revealed a certain stabilization in functional capacity, i.e. the ability that allows you to do a job, do household staff, take care of yourself and so on. These abilities tend to decrease as the disease progresses.

Meanwhile, some researchers have highlighted that the main action of pridopidine was linked not so much to dopamine, but to a receptor called sigma-1 or S1R, involved in helping neurons communicate with each other and survive under stressful conditions. These findings have caused a rethinking of the drug's action in the nervous system. Improving movement control is a symptomatic benefit, while extending neuronal survival modifies the course of the disease, potentially slowing its progression.

The rights to pridopidine have been transferred to a new company, Prilenia Therapeutics, that launched the PROOF-HD study in 2020.

Unfortunately, the results that Prilenia officially communicated today are not entirely positive.

The primary endpoint of PROOF-HD has not been achieved: the drug has not been shown to slow the progression of Huntington's disease and therefore cannot be marketed, or at least not in a short time. The secondary objectives, unfortunately also not achieved, were aimed at show the efficacy of the drug on cognitive abilities and motor skills.

In its press release, Prilenia states that the efficacy of pridpidine was lower than expected in patients who were also taking concomitant medicines, in particular neuroleptic drugs and drugs for the treatment of chorea, while in the others it showed, at various times, clinically benefits and significant effects on the progression of the disease and on cognition, motor ability and functional ability.

"It is difficult to accept this umpteenth defeat of a drug in which so many have believed and still believe", says Ferdinando Squitieri, Scientific Director of the LIRH Foundation. "Although it unfortunately did not meet its primary objective, pridopidine still showed, once again, a clinical benefit on motor coordination measured with a sensory and objective system called Q-Motor."

The HD community is resilient and will deal with this disappointment as well.

Prilenia will continue to further its investigations into the drug pridopidine, and we will support any efforts that appear to us to have a solid rationale.

Many new opportunities will soon open new and encouraging scenarios.

Next Thursday 4 May at 4.30 pm we will organize a meeting via zoom to explore the results of the study and their implications, which will be presented by our Scientific Director, Prof. Ferdinando Squitieri. This is the link to participate.

Attached to this page, you will find the letter we received from Prilenia, with a link to the official press release.