EHDN statement: Next steps in the development of Ionis/Roche HTTRx antisense oligonucleotide (ASO) program for Huntington’s disease

Many in the HD community are now aware of the initial IONIS-HD HTTRx clinical trial results and have questions. EHDN Central Coordination have compiled the following statement for anyone interested.

What do the results of the HTTRx trial mean?

This is a really useful first step in developing a new treatment for HD. So far we have only seen the information in the press release from Ionis Pharmaceuticals, Inc., but it looks like levels of the huntingtin protein can be lowered in cerebrospinal fluid when the ASO drug is given to adults with early manifest HD. It appears that the extent of this reduction is dependent on the dose of the drug (the higher the dose, the greater the decrease in huntingtin protein), which strongly suggests that the drug is targeting the right gene product.

However we must be cautious, and these results certainly do not yet represent evidence of an effective treatment. We think that huntingtin protein levels are reduced in the cerebrospinal fluid because the drug gets to and acts in the brain. But we don’t know how much of the drug reaches and works in the parts of the brain which are most affected in HD, and we don’t know whether the amount of huntingtin protein lowering is sufficient to offer clinical benefit and lead to a real change in HD patients’ lives. We also don’t yet know whether the dosing regimen used so far is the right one, or whether the treatment has been given at the optimal stage of disease. Answering these questions will require further clinical trials that follow more people over a longer time period. These next trials will probably not start until late this year and will take several years to complete.

Is it possible to get a prescription for the new drug or be given the drug at an HD centre?

While the results of the Ionis HTTRx ASO trial are encouraging, there is not yet an approved drug that can now be prescribed. A number of the questions mentioned above need to be answered before starting the regulatory process that must be followed before doctors can prescribe any drug to patients. This means it is also not possible to receive the treatment at an HD centre outside of a clinical trial.

Who can participate in the upcoming clinical trials?

We expect there will be more trials of this particular ASO over the next few years. We hope that many of the EHDN sites will be chosen to participate in these trials, although we can’t guarantee this. It is likely that the next trial of the Ionis HTTRx ASO drug will include people with early manifest HD – just like the trial that has just finished. These trials are only now being planned so it’s not possible to say who might be eligible for them. If the trials do involve EHDN sites we will endeavour to be as transparent as possible regarding the participant selection process.

What can be done now?

The best thing that patients, families and the wider HD community can do now is to keep informed about the latest developments. The HDBuzz website ( is a great way to do this, with their track record of honesty and integrity.

Interested persons can get involved in other HD research too. Many EHDN sites invite people into clinical studies and trials who are already in the Enroll-HD global observational study. Please visit  to find out more about participating in Enroll-HD.

Finally, some notes of thanks.

Thanks should be extended to:

  • those individuals who agreed to be the first humans ever to be injected with this experimental drug, without being sure of its effect,
  • the research teams around the world who conducted the trial and collected high-quality data,
  • Ionis Pharmaceuticals, the company who designed the drug and the trial; CHDI Foundation, the nonprofit organization that supported the preclinical development of the drug; and Roche, the company that will lead the drug’s future development.

Best wishes,

EHDN Central Coordination