Neurocrine Tanks as Tourette Syndrome Drug Flunks Mid-Stage Study

Published: May 24, 2017

Neurocrine Tanks as Tourette Syndrome Drug Flunks Mid-Stage Study May 24, 2017
By Alex Keown, Breaking News Staff

SAN DIEGO – Shares of Neurocrine Biosciences, Inc. are down more than 8 percent this morning after its Phase II Tourette syndrome drug Ingrezza (valbenazine) failed to meet its primary endpoint due to what the company said was inadequate dosing.

This was a major stumble for Ingrezza, which just last month garnered approval by the U.S. Food and Drug Administration for the treatment of adults with tardive dyskinesia, a disorder marked by uncontrollable, abnormal and repetitive movements of the trunk, extremities and/or face.

In its Phase II trial for Tourette, Neurocrine investigators said the exposure-response analysis showed that selected doses for the study were below the therapeutic range for adequate tic reduction in the majority of pediatric subjects. "This study showed that we underestimated the Ingrezza dose needed for the pediatric population but also provided us with a clear-cut view into the level of dosing required for future studies," Christopher O'Brien, chief medical officer of Neurocrine, said in a statement.

By pinpointing inadequate dosing, Neurocrine has said it will move forward with another clinical trial, but this time with better dosing levels for patients. In its statement, Neurocrine said there was a “substantial reduction in tics” for the subset of subjects with an appropriate range of doses. However, for the patients with “sub-therapeutic exposure,” tic reduction was comparable to placebo.

The pre-specified primary endpoint for the Phase II Tourette’s trial was the change-from-baseline between the placebo and active groups in the Yale Global Tic Severity Scale at six weeks in the intent-to-treat (ITT) population, the company said. The T-Force GREEN study was a randomized, double-blind, placebo-controlled, multi-dose, parallel group, Phase II study of 98 children and adolescents. Patients received once-per-day doses of the drug.

"We have developed a complete exposure-response model from this study that we believe accurately defines the appropriate dose-range to be tested in the next clinical study that will be started later this year,” O'Brien added.

While O’Brien put a positive spin on the data, EndpointsJohn Carroll remained skeptical. Writing this morning, Carroll said subset data “are often not substantial enough to provide anything more than an indication. And they can be woefully misleading.”

Ingrezza is a selective VMAT2 inhibitor. The company said it is thought to work by reducing the amount of dopamine released in a region of the brain that controls movement and motor function. It was that success that earned it FDA approval for TD earlier this year. Ingrezza is the only FDA-approved product for treatment of adults with tardive dyskinesia. Some analysts have predicted Ingrezza will generate $1 billion for its approved TD use. The drug has an expected (pre-consumer) price tag of about $10,000 per month.

In addition to the Phase II Tourette’s trial, Neurocrine is also conducting an open-label, fixed-dose study of Ingrezza for about 180 Tourette’s patients—a mix of children, adolescents and adults who have completed one of two other Neurocrine Tourette’s trials. This Phase II study will assess the long-term safety and tolerability of Ingrezza in children and adults with Tourette syndrome.

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