Researcher explains the development of Ingrezza for tardive dyskinesia.
Chris O’Brien, MD, is the chief medical officer at Neurocrine Sciences, Inc., and was part of the research team that developed valbenazine (Ingrezza) for the treatment of tardive dyskinesia. MD Magazine® editors interviewed O’Brien at the 69th American Academy of Neurology Annual meeting in April about the availability of the first treatment for the disorder.
How will the recent drug approval for tardive dyskinesia affect patient care?
tardive dyskinesia is one of those conditions which is more common than I think most people realize. It affects more than 500,000 people in the U.S. The challenge is these involuntary movements. They affect the mouth, the tongue, the jaw, the limbs, the trunk. They add to the stigma of mental illness. This is really hard for patients because often the result is social isolation. Other people are very uncomfortable near individuals who are already dealing with depression, bipolar disorder, schizophrenia, and now they have these involuntary movements to add to that layer of discomfort with everybody around them. It’s true that the involuntary movements sometimes cause physical disability — biting the tongue, falling – but more often it’s that social isolation. Treatment of TD can improve the impact of TD on these very complicated patients.
How exactly will Ingrezza be used in practice?
We imagine that two groups of doctors will be using Ingrezza for the treatment of TD: neurologists and psychiatrists. The psychiatrists are the ones who are treating patients with underlying psychiatric disease on a day-to-day basis. They would simply now have an option of adding this medication to the program. Neurologists typically get referred the complicated patients with the very unusual movement disorders, trying to understand what the condition is. They’re more able to say, ‘This is really TD,’ or ‘This is some other neurologic condition and here is how Ingrezza can be used.’
Were there particularly striking findings over the course of the study?
We knew more than ten years ago that targeting this protein in the brain called VMAT2 could help regulate the dysfunctional movement control system in the basil ganglia. What we had to do was come up with a molecule that did that and only that. It would have no other what we call off-target pharmacology effects. The first couple of years were spent going through hundreds of molecules to find the one that became valbenazine, with the brand name Ingrezza. The next steps were getting it through all of the hurdles of what’s called pre-clinical safety testing. We then took the molecule for the first time into a human in 2009. Since that time, we’ve conducted over twenty clinical trials in patients to get where we are today. There were a lot of hurdles. The clinical trials for tardive dyskinesia had never been done to get a drug approved. We had to figure out how to design and run the trials, how to measure the Dyskinesia, and that was a major challenge.
Did you experience pushbacks?
We had setbacks, not pushbacks. I have to say as a neurologist who works in drug discovery and development, I’ve worked with the FDA on a number of different projects over the years. In this situation, the division of psychiatric products at the FDA was very engaged. They were absolutely committed to help get a treatment to patients. And so, there were setbacks, but not pushbacks. The setbacks had to do with figuring out how to actually design and run the clinical trials and get them to read out properly.