Roche announced that the European Medicines Agency (EMA) has granted Prime (PRIority MEdicines) designation for the company’s investigational medicine RG6042 (formerly known as IONIS-HTTRx) for the treatment of people with Huntington’s disease (HD).
RG6042 has demonstrated its ability to reduce the toxic mutant huntingtin protein (mHTT), which is believed to be the underlying cause of HD, in a phase I/IIa study. Prime is a designation implemented by the EMA to support data generation and development plans for promising medicines, providing a pathway for accelerated evaluation by the agency, and thus potentially enable them to reach patients earlier.
“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,” said Sandra Horning, MD, Roche’s Chief Medical Officer and Head of Global Product Development. “Preliminary data on RG6042 were the first to show that levels of toxic mutant huntingtin protein can be lowered in adults with Huntington’s disease, and we are working closely with the EMA and other health authorities to initiate a global phase III study as soon as possible.”
PRIME designation for RG6042 is primarily based on the data from an exploratory phase I/IIa trial of RG6042 that demonstrated a significant reduction in mHTT, which breaks down the nerve cells in the brain. The study demonstrated a mean 40% (up to 60%) reduction of the specific HD protein in the cerebrospinal fluid (CSF) of adult patients treated with RG6042 for three months at the two highest doses. Furthermore, levels of mHTT measured in the CSF were still declining in the majority of treated patients (70%) as of the last measurement in the study. RG6042 was well tolerated in this short initial study. These data were shared at the CHDI 13th Annual HD Therapeutics Conference in March 2018, and updated results were presented at the American Academy of Neurology (AAN) Annual Meeting in April 2018.
Roche will initiate a pivotal phase III study to evaluate RG6042 in a larger patient population to further characterise the safety profile and determine if it can slow the progression of HD in adults.
RG6042 is a second-generation modified antisense oligonucleotide (ASO) designed to reduce the production and levels of mHTT protein by targeting human HTT mRNA.5 RG6042 is the result of a comprehensive drug discovery programme between Roche and Ionis Pharmaceuticals focused on optimising the potency, specificity and tolerability of an ASO targeting human HTT mRNA. RG6042 is the most advanced compound in clinical development to target toxic mutant huntingtin protein (mHTT), which is believed to be the underlying cause of HD. Treatment with RG6042 has the potential to slow or stop disease progression in all people with HD.
Huntington’s disease is a rare genetic, progressive condition that causes the nerve cells in the brain to break down, which severely affects a person’s everyday functions such as mobility and thinking. It has a devastating impact on people living with the disease, and the hereditary nature of HD means it profoundly affects entire families. As the disease progresses, people with HD may develop personality changes, difficulty walking and swallowing, as well as having a significant cognitive impact. Survival ranges from approximately 10-20 years following motor onset of the disease.
There is no known cure for HD and no approved therapies that treat the underlying cause. The estimates for the number of people affected by Huntington’s vary between geographic regions. Huntington’s disease is the most common monogenic neurological disorder in the developed world, with an estimated prevalence of 3.5–7/100,000 in North America, Western Europe, and Australia.