The stated cause of the suspension of enrollment was the occurrence of two intrathecal catheter-related infections that weren’t related to the drug.
Roche suspended a Phase I trial of an RNA drug, tominersen (RG6042), originating from Ionis Pharmaceuticals to treat Huntington’s disease. The stated cause of the suspension of enrollment was the occurrence of two intrathecal catheter-related infections that weren’t related to the drug.
In December 2017, Roche licensed IONIS-HTTRX from Ionis, renaming it RG6042. The therapy is designed to target the underlying cause of Huntington’s disease (HD) by decreasing production of the toxic mutant huntingtin protein (mHTT). The first patient enrolled in the trial on January 28, 2019.
According to the Huntington’s Disease Society of America, Huntington’s disease (HD) is a fatal disease that causes progressive deterioration of nerve cells in the brain. There is no cure. It is an inherited disease, with every child of a parent with HD having a 50/50 chance of inheriting the mutated gene. In the U.S. there are about 41,000 symptomatic patients and more than 200,000 at risk of inheriting the illness. The symptoms of HD have been described as having ALS, Parkinson’s and Alzheimer’s simultaneously. They usually appear between the ages of 30 and 50 and grow worse over a 10 to 25-year period. Eventually the patient dies of pneumonia, heart failure or other complications.
Although not many details are given about the suspension of the trial, the clinicaltrials.gov website says it was not related to the drug itself. As a result, no other trials for the drug appear to be impacted, including an international Phase III trial that is expected to present topline data in 2022.
In a note to investors, Mani Foroohar, an analyst with SVB Leerink, wrote, “Suspension of this study should have no impact on the pivotal GENERATION-HD1 study—the pivotal study administers drug through intrathecal injection with no attendant use of this catheter—and this smaller study was likely suspended in order for Roche to modify the protocol to reduce the time the catheter is in the patient, or otherwise improve procedural technique.”
Tominersen is an antisense drug, which Ionis focuses on developing. Antisense drugs typically contain part of the non-coding strand of messenger RNA (mRNA), which is involved in translating DNA into proteins. The antisense drugs attach to the mRNA and inactivate it, which prevents the particular gene from churning out whatever protein it codes for. Tominersen is designed to decrease the production of huntingtin, the protein that causes Huntington’s disease.
In a February update of the program, Sara Tabrizi, professor of clinical neurology at University College London, director of the UCL Huntington’s Disease Center and an investigator for the tominersen clinical trials, said, “I am pleased by the progress that Ionis, Roche and the HD research community continue to make in pursuit of a potentially effective treatment for this progressive, incurable and ultimately fatal disease that affects thousands of people worldwide. While much work remains to be done, tremendous strides have been made and I am heartened by the courage of all the HD patients and families who are participating in the studies.”
Preliminary data from a 15-month open-label extension (OLE) study of RG6042 supported the conclusion that an infrequent dosing schedule of about every two months met or exceeded the level of mHTT protein lowering predicted in CNS tissues. The early data also described electroencephalography (EEG) data from a Phase I/II trial compared to EEG data in health controls. In HD patients, EEG brain activity is abnormally low, but treatment with tominersen appeared to reverse the deficit in brain activity.
