Potential breakthrough drug for Huntington’s to enter advanced clinical testing

Potential breakthrough drug for Huntington’s to enter advanced clinical testing

Publication date: Sep 18, 2018

A potential breakthrough drug for treating Huntington’s disease from Carlsbad’s Ionis Pharmaceuticals will begin an advanced clinical trial early next year. If successful, the trial could lead to marketing approval.

Ionis partner Roche, which is handling the clinical trials, made the announcement Sunday. The trial will take place globally.

Huntington’s disease is an incurable and invariably fatal neurodegenerative disease caused by mutations in one gene. More than 30,000 Americans have the mutation, and either have the disease or will eventually develop it.

The age of onset varies with the mutation’s severity. Most often, symptoms appear in middle age. These include uncontrollable movements and problems with emotions and cognition, along with changes in personality. In advanced cases, patients have trouble speaking or swallowing.

Existing treatments only manage symptoms. There is no treatment that stops or even slows down the disease’s progression.

The mutation causes production of an abnormal form of a protein called huntingtin, which is essential for brain development. It is genetically dominant, meaning that only one copy of the gene, inherited from either parent, causes Huntington’s.

The drug, RG6042, (originally IONIS-HTTRx) inhibits production of the mutant huntingtin. It uses an Ionis technology called antisense, which blocks or changes genetic activity. All Ionis drugs use antisense.

Inhibiting production of the protein in theory should slow, stop or even reverse the disease. Early clinical testing has shown that the drug does inhibit huntingtin production and provided preliminary evidence of some benefit. But efficacy can only be proven by the more advanced trial.

Success -would be a historic moment for Huntington’s disease patients, their loved ones and the health care providers who treat and take care of HD patients,” said C. Frank Bennett, senior vice president of research at Ionis, in a statement. -It also would be an important advance for the neurodegenerative field in general.”

Ionis has already successfully developed a drug effective against another previously untreatable neurological disease, spinal muscular atrophy, which in its severest form can kill in infancy. Called Spinraza, it’s sold by partner Biogen.

Ionis is also developing drugs for Alzheimer’s and ALS, two other incurable and fatal neurodegenerative diseases.

Ionis developed RG6042 in collaboration with researchers from the lab of Don W. Cleveland at UC San Diego. It is injected into the spinal fluid, enabling it to reach the brain. Roche licensed the drug last December, assuming the lead in development.

The trial will be double-blinded, meaning that neither doctors nor patients will know who is getting the drug and who is getting a placebo. The drug – or placebo – will be given to up to 660 patients manifesting Huntington’s symptoms over 25 months, Roche said in its announcement. They will be treated at about 80 to 90 sites worldwide.

More information on the upcoming Phase 3 trial once it gets underway, along with trials of other Huntington’s drugs, can be found at www.hdtrialfinder.org and www.clinicaltrials.gov. In addition, Kenneth Serbin, a San Diegan who carries the mutation, writes about Huntington’s at to face with Pope Francis on Huntington’s disease

Sustained Therapeutic Reversal of Huntington’s Disease by Transient Repression of Huntingtin Synthesis

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