EHDN Virtual Conference – September 2021

EHDN Online Plenary Meeting 2021

Having listened to the presentations about ongoing and upcoming clinical trials during the EHDN virtual conference has filled me with renewed enthusiasm and energy – Says Astri Arnesen, EHA President .

We were all hit by the setbacks in Roche and Waves trials earlier this year. But during the conference it has been demonstrated again and again that the work continues in a very good pace.  

Below you find a short list with the most exciting progress about ongoing trials and the ones that are close to start recruit participants:

First patient was dosed in August with the new drug called WVE3.  The new trial is called Select-HD and is a Phase 1b/2a trial.  36 participants in early stages of HD will be recruited.  Vissia Viglietta told in her presentation that they have done several improvements in their drug and that that WVE3 is a more potent and have stronger knockdown effect on the mutant huntingtin. 

Another important aspect with WVE3 is that it aims to target only mutant huntingtin while leaving the healthy untouched. To be able to identify only the mutant protein, they are using so-called snips (SNP) and WVE3 binds to SNP3 which is expected to be present in around 40% of HD patients.  You can read Waves press release about the trial initiation here.

Michael Hayden told in his presentation that recruitment in the PROOF-HD study is going very well.  The company expect to have all 480 participants active in the trial by the end of this year. In this study the participants gets either the active drug Pridopidine or placebo by taking a pill twice a day.  

Duration of the trial will be between 65 and 78 weeks.  Prilenia aims to have the results analyzed and able to apply for approval in the fall of 2023.  You can read more about the trial here.

Beth Borowsky presented the upcoming trial with Branaplam, a drug that has already been tested on children with SMA. 

Branaplam has proven to lower Huntingtin in lab and animal studies. It has already been tested in a Phase 1 trial on healthy volunteers.  And tests showed that Huntingtin was reduced in the participants after a single dosing of the Branaplam.  Branaplam is taken orally by swallowing a capsule. 

Novartis is now ready to do a Phase 2b study – to explore safety and mHTT lowering and the potential for slowing disease progression.  Participants will get the drug or placebo once a week.  20% will have placebo.  The trial will run for 16 weeks and the participants will be split in groups and each group will receive different doses. After the 16 weeks all participants will be offered Open Label Extension, which means they will be offered the active drug at the dose that seems best, based on the trial results. 

Novartis aims to have the first patient in by the end of 2021 and will have sites in UK, Germany, France, Spain, Russia, Italy, Belgium, Lithuania and Hungary.

Maurice Zauderer, President and CEO of Vaccinex, said in his presentation: I believe our drug Pepinemab, delays or halts cognitive decline in HD

Vaccinex did a trial called Signal which was terminated in the fall 2020 and unfortunately they didn’t reach significant effect. But after studying the results closely they saw that a subgroup of participants had significant effect on cognitive measures. 

This was the case for those who were a little more into the disease and had more symptoms (scored 11 or less on Total Functional Capacity score where 13 is no symptoms)  than the ones in a very early phase or prodromal phase of HD.  The images of the brain (MRI) showed that the treated individuals had less loss of brain tissue than the ones who had received placebo.

Vaccinex has therefore plans to proceed with a Phase 3 trial with participants that are slightly more advanced in their disease than the earliest phase and with a larger number of cognitive tests as the primary outcome, which means that the effect should be measured against several test results combined  and not just two, as they had in Signal. 

Brian Pfister, talked about their drug called PTC518, which is orally administered.  The company has started a Phase 1 trial with healthy volunteers. In this trial they have seen that the participants who received the highest dosing of the drug, had a 50% reduction of Huntingtin. When testing the drug on monkeys they saw that the blood brain barrier was passed and the drug distributed in the brain. 

The effect is reversed after a few hours and is more or less out of the body after 72 to 96 hours.  Because the drug is taken orally it is lowering Huntingtin not just in the brain, but also all other parts of the body.  PTC aims to move into a Phase 2 trial later this year in multiple countries.

A newcomer in the HD community was also presenting very exciting news during the conference.  Catherine Scart-Grès from SOMBiotech, a Spanish company, told us that they will do a Phase 2b trial with 129 patients.  The trial will involve more than 20 European sites and is expected to start by the end of 2021.

The participants will be split in 3 groups or arms as its often called in trials. 1 group will get placebo, the second group will receive a 200 mg dose of the drug and the third group will receive a dose of 300 mg dose.  The drug is taken orally twice a day. 

The main “target” for this drug is to reduce chorea, but there are also expectations that it may have a positive influence on psychiatric symptoms. 

SOM Biotech has done a phase 2a trial with 32 HD patients.  In this trial they did see improvement in the motor tests in 57% of the participants that received the active drug.  All the 32 participants are offered to continue in the study in an open-label extension where they all get the active drug

Voyager Therapeutics has for quite some time planned to do a trial in HD with their gene therapy.  Their approach is a bit similar to Uniqure and it was planned to provide the drug through injections into the brain.  Voyager recently announced that they have paused the plans.

This is not done because they have lost faith in the potential to treat HD with their drug.  The reason is that they aim to deliver the drug through spinal injections and not brain surgery.  This is a much easier procedure and will enable more clinics to provide the treatment, if the drug is approved.