IONIS-HTTRx Shows Promising Results in Phase 1/2 Clinical Trial

Marta Figueiredo PhD avatar

by Marta Figueiredo PhD |

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Ionis Pharmaceuticals‘ experimental therapy IONIS-HTTRx significantly reduced levels of the protein responsible for Huntington’s disease (HD) in early stage patients, according to top-line results from a Phase 1/2 clinical trial.

The data, presented at the 13th Annual HD Therapeutics Conference in Palm Springs, California, confirm IONIS-HTTRx as the first therapy in development to lower the disease-causing protein in Huntington’s patients.

Huntington’s is caused by mutations in the huntingtin (HTT) gene that result in the production of an abnormal and toxic protein called mutant huntingtin (mHTT). The mutant protein gradually destroys neurons in the brain, leading to deterioration of mental abilities and physical control.

Among the brain areas most affected by this disorder are the cortex, which has a key role in memory, perception, cognition, thought, language, and consciousness, and the caudate region, which is involved in motor function, language, memory, and learning.

IONIS-HTTRx, also called RG6042, was designed to reduce the production of all forms of the huntingtin protein, including the mutated one. This raises the possibility of treating all Huntington’s patients, regardless of their individual HTT mutation.

Promising results from preclinical studies led to the initiation of the Phase 1/2 study (NCT02519036), which evaluated the safety, tolerability, properties and movement within the body of IONIS-HTTRx in patients with early-stage Huntington’s disease.

The 13-week, randomized, placebo-controlled, dose escalation study enrolled 46 patients aged 25-65. Participants were assigned randomly to receive one of five different doses of IONIS-HTTRx or a placebo, given monthly through the spinal canal, for a total of four doses.

Participants who received either of the two highest doses of the treatment showed an average reduction of 40% in mHTT levels in their cerebral spinal fluid. Some patients experienced an even greater reduction, as high as 60%.

Based on a predictive model developed from preclinical data, researchers believe these reductions correspond to an estimated 55-85% decline of mHTT levels in the brain cortex, and 20-50% in the caudate region. More importantly, the preclinical work suggests these reductions are big enough to yield clinical benefits.

“In this study, we were able to achieve mutant huntingtin protein reductions (…) that were higher than those that produced disease benefit in preclinical models of HD,” C. Frank Bennett, senior vice president of research at Ionis Pharmaceuticals, said in a press release.

With protein levels still declining at the end of the study, Ionis expects to see further reductions, with a maximum decline at six months after the first dose.

Regarding safety of IONIS-HTTRx, no serious adverse events were reported and most adverse events were mild and considered to be unrelated to the therapy.

“With IONIS-HTTRx (RG6042)the HD community has new hope for a therapy that can reduce the cause of HD, and therefore, may slow the progression and potentially prevent the disease in future generations, which is truly groundbreaking,” added Sarah Tabrizi, MD and the study’s lead author.

Since this was a small and short trial, the next step is to conduct larger and longer studies to confirm these results, to investigate whether IONIS-HTTRx slows disease progression, and evaluate long-term safety.

Ionis and Roche are initiating an open-label extension trial (NCT03342053) for the 46 participants who completed the Phase 1/2 trial. The extension study will transition to Roche, which will manage this trial and future studies of IONIS-HTTRx.


Tonia B avatar

Tonia B

This progress is beyond exciting. Thankyou for reporting on this update. I look forward to hearing the outcomes of the next stage of the Roche trial.

Andrew avatar


My niece and her son have HD. Looking forward to treating them. If I had this disease, I would take the treatment immediately.

Sylvia hall avatar

Sylvia hall

Is this treatment being given in the uk and if so would it be considered for a 77year old female. There is no record of this disease ever having been in the family.this lovely lady is my cousin and I love her very much. She has had an brain scan and has just had blood test. Although she has not had any results from these, the nurse at the blood test dept gave her a print ou of hodkinson disease. She is now awaiting an appointment with the neurologist for the results. Thanking you in anticipation of an early response .

Tom Marciniak avatar

Tom Marciniak

My husband was diagnosed 3 yrs. ago with huntington's disease. Would you still be taking volunteers for clinical trial of Ionis? If so, he would be greatly interested. Thank you. We live outside Toledo, Ohio

bob avatar


When can we start?

Joaquin Quintero avatar

Joaquin Quintero

No saben lo ansioso que estoy de que sea una ayuda definitiva, pues el sufrimiento que le ha causado a mi mama y a mi como hijo es indescriptible... no se lo deseo a nadie, de verdad ojala sea pronto... adicional alguien sabe si se puede acceder a este tratamiento en estado de fase?

AhmadFotoohi avatar


Hi dears.
Do you know how we can participate in this trial? Please answer me through [email protected] or here

ed clark avatar

ed clark

Very exciting! Do have any information on next round of clinical study locations and recruitment/enrollment?

James Bowery avatar

James Bowery

Unfortunately, the upcoming clinical trial is limited to 600 patients and there are far more HD victims than 600. For the majority of HD victims, this limitation is not critical since they are at an early stage in the development of symptoms, and they will receive the treatment before their decline is devastating. For others, such as my wife, delay may well be a death sentence.

Helidiane Francisco de Almeida avatar

Helidiane Francisco de Almeida

Saudações. Tenho 33 anos, advogada, mãe de 3 filhos. No dia 02/04/2018 descobri que dois de meus filhos são portadores. Atualmente, possuem 5 e 3 anos de idade. O pai descobriu em 2017 que e portador. A avó materna descobriu em 2016. Preciso de ajuda. Estou disposta a qualquer coisa e também a ajudar no que for preciso. Estou em busca da cura!!! [email protected]

Helidiane Francisco de Almeida avatar

Helidiane Francisco de Almeida

Greetings. I am 33 years old, lawyer, mother of 3 children. On 02/04/2018 I discovered that two of my children are carriers. They are currently 5 and 3 years old. The father discovered in 2017 that he is a bearer. The maternal grandmother discovered in 2016. I need help. I am willing to do anything and also to help in whatever it takes. I'm in search of the cure!!! [email protected]

Angie vanover avatar

Angie vanover

Did you have your young children tested? We have three small children at risk and we were told we can’t test them until they are 18. Ty for any info you have on this.

Judith A Overman avatar

Judith A Overman

I have been tested my cag 39-22 my mother age 92 is 39-18, her brother my uncle was 39-17, his son my cousin was 42-22. We believe their mom my grandmother had huntington's disease but passed before the test was available. I will be 64 and willing to be used for your research to find a cure. My father had sun downers and passed away 2 years ago at age 92. I believe I will have a few years to test progression of disease. I have no balance, falling, taking antidepressant meds.

angie guarnizo avatar

angie guarnizo


I was diagnosed with Huntington a yr ago. I would like to know if I can participate in any Clinical Trial.


Angie G

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