IONIS-HTTRx is a potential treatment for Huntington’s disease that Ionis Pharmaceuticals created.

It licensed IONIS-HTTRx to Roche in late 2017, making Roche responsible for the further development and commercialization of the therapy.

How IONIS-HTTRx works

Huntington’s disease, an inherited disorder that affects nerve cells in the brain, is caused by a mutation of the HTT gene, which generates the huntingtin protein.

Scientists believe the abnormal form of the protein that the mutation produces causes gradual destruction of nerve cells. People with Huntington’s have problems thinking and controlling their movements that worsen over time.

It is an antisense therapy. It targets messenger RNA, a molecule that is an intermediary between DNA, the cell’s genetic material, and the huntingtin protein. Cells use the message as a template to produce the protein. It is designed to stick to a faulty HTT gene’s messenger RNA, reducing the amount of abnormal huntingtin protein the gene generates.

IONIS-HTTRx in clinical trials

Ionis completed a Phase 1/2a clinical trial (NCT02519036) of IONIS-HTTRx in late 2017. The study covered 46 patients at nine centers in Britain, Germany, and Canada. They were randomly assigned to either receive IONIS-HTTRx in increasing doses or a placebo. The treatment was administered to participants’ spinal canal.

The study looked at IONIS-HTTRx’s pharmacokinetics, or how it was distributed and metabolized in the body, as well as its pharmacodynamics, or mechanism of action.

Ionis said in a December 2017 news release that IONIS-HTTRx’s safety in the trial, and patients’ ability to tolerate it, supported the therapy’s continued development. A key finding was that as the dose of IONIS-HTTRx was increased, levels of mutant huntingtin protein in the participants’ cerebral spinal fluid decreased.

Ionis and Roche have started an extension trial (NCT03342053) for patients who completed the Phase 1/2a trial. Expected to run through September 2019, it will further examine the drug’s safety, patients’ ability to tolerate it, and its pharmacokinetics and pharmacodynamics. Investigators will continue measuring levels of mutant huntingtin protein and assess participants’ thinking ability. Participants will be assigned to one of two groups. One will receive a low dose and the other a high dose of IONIS-HTTRx.



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