Ground breaking treatment of Huntington's disease discovered

An experimental antisense drug of Ionis Pharmaceuticals -- Ionis-HTTRx -- was found to successfully lower the mutant huntingtin protein (mHTT) levels in the spinal fluid of Huntington's disease patients, in the first human trial.

Ionis-HTTRx is designed to reduce the production of all forms of the huntingtin (HTT) protein, which in its mutated variant is responsible for Huntington's disease. It has been granted orphan drug designation by the US Food and Drug Administration and by the European Medicines Agency.

Huntington's disease is a rare, genetic, progressive neurodegenerative disease resulting in deterioration of mental abilities and physical control. Symptoms of HD usually appear between the ages of 30 to 50 years and continually worsen over a 10- to 25-year period. Ultimately, the weakened individual succumbs to pneumonia, heart failure or other complications. Presently, there is no effective disease-modifying treatment for HD, and current products focus only on managing disease symptoms.

"The results of this trial are of ground-breaking importance for Huntington's disease patients and families. For the first time a drug has lowered the level of the toxic disease-causing protein in the nervous system, and the drug was safe and well-tolerated," Sarah Tabrizi, director of the University College London Huntington's Disease Centre and global chief investigator of the phase 1/2a study of the drug, said in a statement issued by the university.

"The key now is to move quickly to a larger trial to test whether the drug slows disease progression," said Dr. Tabrizi.

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"This is very big news for the HD [Huntington's disease] community," George Yohrling, senior director, mission and scientific affairs for the Huntington's Disease Society of America (HDSA), told Medscape Medical News.

The trial enrolled about 46 patients having early Huntington's disease at nine study centers in the U.K., Canada, Germany, and Canada. They were given our doses of Ionis-HTTRx or placebo through injection in the spinal fluid. According to the ascending-dose trial design, the dose of Ionis-HTTRx was increased several times during the trial.

Key Results of the Trial:

• Treatment with Ionis-HTTRx led to significant, dose-dependent reductions in mHTT — the first time the protein known to cause Huntington's disease has been lowered in the nervous system of patients.


• The drug was safe and well tolerated, as judged by an independent safety committee, which "supports continued development.

he drug was safe and well tolerated, as judged by an independent safety committee, which "supports continued development," Ionis said in a news release. An open-label extension study for patients who completed the phase 1/2a study is underway.

"We are encouraged by the performance of Ionis-HTTRx in the Phase 1/2a clinical study. The dose-dependent reductions of mHTT we observed in the study substantially exceeded our expectations and we were equally encouraged by the safety profile of the drug," C. Frank Bennett, PhD, senior vice president of research at Ionis Pharmaceuticals said in the release.

"The fact that levels of mutant huntingtin were reduced in correlation to the dose of Ionis-HTTRx that was given is significant, and the fact that participants in this first Phase 1/2a study are able to continue on the drug through open-label extension gives us optimism regarding its safety," HDSA President and CEO Louise Vetter said in a statement.

"Ionis' announcement of the completion of the Phase 1/2a study of IONIS-HTTRx is a historic moment in the fight against HD as it represents the successful completion of the first trial to treat the underlying cause of Huntington's disease, the genetic mutation itself," said Vetter.

Ionis and its development partner Roche will present results from this study at medical conferences in the first half of 2018 and plan to submit the study results for publication in a peer-reviewed medical journal.

"As such, Ionis-HTTRx offers a unique approach to treat all patients with Huntington's disease, irrespective of their individual HTT mutation," Ionis notes in the release.