Neurocrine Biosciences, Inc. (NASDAQ:NBIX) just notified markets that the FDA has accepted a new drug application (NDA) for its lead drug candidate, Ingrezza, and alongside the acceptance, has set a PDUFA target action date of April 11, 2017 for the drug. It’s up for priority review, shortening the wait until PDUFA, and chances of approval are pretty good based on data seen to date. There is plenty of potential for upside on an FDA green light, and so ahead of the agency’s decision day, let’s take a look at the drug itself in an attempt to see what is going to factor in to the outcome of the application.
So, as mentioned, it is called Ingrezza, and is targeting an indication of what is called tardive dyskinesia. For those not familiar with this condition, it is associated with involuntary movement of the face and neck, and characterized by lip smacking, grimacing, tongue protrusion, facial movements or blinking, puckering and pursing of the lips. There is no currently available cure.
It is in the same family as Tourette’s syndrome, we will look at this relationship in a more detail shortly.
For now, however, let’s focus on this target indication. The drug is part of a family of drugs called VMAT2 inhibitors. VMAT2 is a protein that is concentrated primarily in the human brain, and is responsible for aiding and monitoring the movement of what are called monoamines – things like dopamine and serotonin – across neurons and synapses. Through the inhibition of this protein, Neurocrine is attempting to limit the degree to which dopamine is transported across neurons, and in turn, relieve the symptoms associated with the disease. Basically, it is believed that this condition comes about as a result of what is called a hyperdopaminergic state, which as its name suggests, is a state associated with too much dopamine activity in the brain.
By inhibiting the movement of dopamine across neurons through the inhibition of the VMAT2 protein, the drug (theoretically) should be able to reduce the amount of time a patient status in hyperdopaminergic state.
So that is the science, how did the drug do in trials?
Well, the data that underpins the application derives from two studies, a phase II called KINECT2 and a phase III called KINECT3. Of these two, the latter accounted for more than two thirds of the patients that made up both trials, so this is going to hold the most water come decision day. As such it’s the one we’ll focus on here.
The pre-specified primary efficacy endpoint was the change-from-baseline in what’s called the Abnormal Involuntary Movement Scale (AIMS) six weeks into the trial, in an 80mg once-daily dosing group, when compared to placebo, and as assessed by a panel of central blinded video raters. The AIMS in the active group reduced by 3.1 points (Least-Squares Mean) more than placebo, with a p-score of p<0.0001. If you’re looking for statistical significance, a p of <0.0001 is what you want.
Safety and tolerability didn’t throw up any serious issues, and the drug hit on a secondary as well as demonstrating significance of dose concentration (which is always a good thing in this sort of trial).
Bottom line, we think there’s a good chance of approval on this one. But that’s not the end of the line.
As promised a little earlier, let’s jump back to Tourette’s. The company is also investigating efficacy as part of a development program in Tourette’s, based on the assumption that the inhibition of VMAT2, and the avoiding of a hyperdopaminergic state, can improve the symptoms of this condition. Any potential in this space will likely serve up some considerable upside on a data dump, as it would also indicate potential in other dopamine related conditions, with one of the leading targets being Parkinson’s.
So there we go.
A strong drug, an unmet need, good data and a near term catalyst. Throw in the kicker of some pending Tourette’s data and this one’s one to watch.