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Ionis drug for Huntington's disease shows early signs of effectiveness

An experimental drug from Ionis Pharmaceuticals safely reduced a toxic brain protein in Huntington’s disease, according to early results in patients. This gives promise that the drug may halt or even reverse the fatal genetic disease, which has never been done.

Based on earlier research, the reduction in the protein should be enough to relieve symptoms, Ionis CEO Stanley T. Crooke said in a conference call Friday.

Ionis is working closely with partner Roche to quickly get the drug into a more advanced clinical trial to measure effectiveness, Crooke said. This could qualify the drug for marketing approval.

Moreover, there is preliminary evidence the drug is effective, a Roche scientist said.

The disease is caused by a mutated form of the brain protein, called huntingtin. This mutation causes the protein to become toxic to brain cells. Symptoms typically arise in middle age or later.

The neural degeneration progressively reduces the ability of patients to move and control their muscles, including the ability to swallow. It can also cause depression and other mental problems. The end is death.

About 30,000 people have Huntington’s disease in the United States, according to the National Institutes of Health. Many others have the mutation, but haven’t yet shown symptoms.

It’s a dominant mutation, meaning that inheriting the mutation from either parent causes the disease.

There are preliminary signs the drug may be effective, Scott Schobel, MD, Roche’s translational medical leader, said in the conference call.

“We have generated some encouraging early correlational signs that need a further confirmation and analysis,” Schobel said, referring to reduction in protein and reduction in symptoms.

Schobel didn’t go into details, saying those interested should “stay tuned” for more detailed information later.

Reductions of about 40 percent were observed in the cerebrospinal fluid of patients given the highest dose of the drug, called Ionis HTTRx. It is injected into the cerebrospinal fluid through a lumbar puncture. Moreover, the level of the toxic protein is still falling, Crooke said.

The 46 patients in the placebo-controlled study are in the early stages of Huntington’s. There were no serious side effects in those given the drug. One placebo-treated patient had a severe event and was hospitalized for observation. No participants dropped out of the study.

The huntingtin protein is essential for normal brain development. But studies have shown it’s not an essential protein in adult animals, Frank Bennett, senior vice president of research at Ionis, said in the conference call.

The early results are reminiscent of another Ionis neurological drug, Spinraza, Crooke said. That drug is also administered through a lumbar puncture. It modifies genetic activity to increase production of a protein needed for motor neurons to survive. Lack of this protein causes spinal muscular atrophy or SMA, which in its severest form can be fatal in infancy.

Spinraza sales for 2017 reached $884 million. It’s marketed by Cambridge-based Biogen, which paid Ionis $113 million in royalties for the year.

Like SMA, Huntington’s has no cure. And if the ongoing study proves successful, Ionis HTTRx will likewise become the first drug that offers the prospect of a near-normal life.

Ionis is also looking forward to potential approval for three other drugs, part of a pipeline of 45 Ionis drugs, Crooke said. All of these drugs work through the antisense technology developed by Ionis, which blocks or modifies genetic activity.

“In short, we're now on the verge of achieving our goal of being a multi-product profitable company,” he said.

Patients and others interested in clinical trials of the Ionis drug can find more information on clinicaltrials.gov by searching for Ionis HTTRx.

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