RG6042 for Huntington Disease Granted PRIME Designation by EMA


IONIS-HTT Rx is the first and only drug to demonstrate reduction of mutant huntingtin protein in patients.

Dr Sandra Horning

Sandra Horning, MD, Chief Medical Officer, Head of Global Product Development

Sandra Horning, MD

The EMA granted priority medicines (PRIME) designation to IONIS-HTT Rx (RG6042), the first drug to demonstrate reduction of mutant huntingtin protein, for the treatment of people with Huntington disease, announced Roche.

The PRIME designation is based on the data from an exploratory phase I/IIa trial of RG6042 which demonstrated a significant reduction in the toxic mutant huntingtin protein.

“We are very pleased that the European Medicines Agency has granted PRIME designation for RG6042, as there is an urgent medical need to find treatment options for families affected by Huntington’s disease,” Sandra Horning, MD, Chief Medical Officer and Head of Global Product Development, Roche, said in a statement.1 “Preliminary data on RG6042 were the first to show that levels of toxic mutant huntingtin protein can be lowered in adults with Huntington disease, and we are working closely with the EMA and other health authorities to initiate a global phase III study as soon as possible.”

In the phase I/II study, 46 subjects with early Huntington disease were treated for 13 weeks with 4 intrathecal injections of 10 mg, 30 mg, 60 mg, 90 mg or 120 mg of RG6042 or placebo, administered monthly.

The study demonstrated a mean 40% reduction of specific Huntington disease protein in the cerebrospinal fluid of adults treated with RG6042 for 3 months at the 2 highest doses, 90 mg (P <.01) and 120 mg (P <.01).

Levels of the mutant huntingtin protein measured in the cerebrospinal fluid were continuing to decline at the last measurement in a majority of patients treated—70%&mdash;and further decreases were anticipated, with a maximum reduction expected by about 6 months after the first dose.

RG6042 was well tolerated and most adverse effects were mild and considered to be unrelated to RG6042; there were no serious adverse effects reported in the treated population.

The second-generation modified antisense oligonucleotide RG6042 is designed to reduce the production and levels of the mutant huntingtin protein, which is believed to be the underlying cause of Huntington disease.

Data from the phase I/IIa study were presented at the CHDI 13th Annual Huntington Disease Therapeutics Conference in March 2018, with updated results presented at the American Academy of Neurology Annual Meeting in April 2018.

RG6042 has also been granted orphan drug designation by the FDA for the treatment of patients with Huntington disease.

"We designed IONIS-HTTRx to treat all patients with Huntington Disease,” C. Frank Bennett, senior vice president of research and franchise leader for the neurological programs, Ionis Pharmaceuticals said in a statement.2 “These important clinical results demonstrate that our approach of targeting the toxic mutant huntingtin protein can significantly reduce the underlying cause of this terrible disease. In this study, we were able to achieve mutant huntingtin protein reductions in study participants that were higher than those that produced disease benefit in preclinical models of Huntington disease."

Roche plans to initiate a pivotal phase III study to evaluate RG6042 in a larger patient population to further study the safety profile and determine if the drug can slow the progression of Huntington disease.

Researchers aim to determine the effects on lowering the huntingtin protein over a longer period of time than the 13-week phase I/IIa study, to find out if any unexpected safety concerns emerge when a larger group of subjects are treated for a longer period of time, and to determine if sustained treatment with RG6042 has an impact on Huntington disease by slowing down the progression.


1. PRIME Designation Granted by European Medicines Agency for RG6042 for Treatment of Huntington Disease [news release]. Basel, Switzerland: Roche; August 3, 2018. https://www.roche.com/de/media/releases/med-cor-2018-08-03.html. Accessed August 3, 2018.

IONIS-HTT Rx (RG6042) Top-Line Data Demonstrate Significant Reductions of Disease-Causing Mutant Huntingtin Protein in People with Huntington's Disease [news release]. Carlsbad, California: Ionis Pharmaceuticals; March 1, 2018. https://www.prnewswire.com/news-releases/ionis-htt-rx-rg6042-top-line-data-demonstrate-significant-reductions-of-disease-causing-mutant-huntingtin-protein-in-people-with-huntingtons-disease-300606962.html. Accessed August 3, 2018.

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