Reaction and Benefits of Deutetrabenazine One Pill, Once-Daily Tablet Approval

Rakesh Jain, PhD, MS

Deutetrabenazine (Austedo XR; Teva Pharmaceuticals), a vesicular monoamine transporter 2 (VMAT) inhibitor, was originally approved as a twice-daily treatment for chorea associated with Huntington disease (HD) in April 2017 and later had its label expanded in August 2017 to include the treatment of tardive dyskinesia. Chorea is characterized by involuntary, dance-like movements that affect the muscles of the body, especially the arms, legs, face, and tongue. Other symptoms of chorea include muscle rigidity or contracture, slow or unusual eye movements, difficulty walking, keeping balance or posture, and difficulty speaking or swallowing.

Deutetrabenazine, both in its original formulation and extended-release option, was the first VMAT2 inhibitor approved by the FDA for the treatment of tardive dyskinesia and chorea associated with HD. Recently, in late May, the FDA approved a new one-pill, once-daily tablet administration option for the therapy, giving it 4 new dosage strengths (30, 36, 42, and 48 mg). The decision ultimately allows for greater administration flexibility and improved adherence for patients with HD, who already struggle with pill tolerance.

Following the approval, NeurologyLive^® sat down with Rakesh Jain, PhD, MS, a clinical professor of psychiatry at the Texas Tech University School of Medicine, who described how the decision impacts the clinical and patient communities alike. Jain gave thoughts on some of the advantages deutetrabenazine brings, the importance of treating chorea and tardive dyskinesia, and some of the unmet needs patients with HD currently face. He also provided perspective on some of the promising safety aspects of the therapy, and how it may be administered with no time or food restrictions.

NeurologyLive: What does this new approval bring to patients with Huntington disease and those with tardive dyskinesia?

Rajesh Jain, MD: As you already know, tardive dyskinesia and Huntington are pretty big challenges, and pill burden is a substantial issue with both of these two populations. The approval of Austedo XR (deutetrabenazine) as one pill, once a day across the therapeutic dose range is, I think, a strikingly big deal for three sets of people. Of course, the most important is patients. With patients and the pill burden, that reduced number of pills a day really improves adherence and compliance. But the other is the family. Both groups have patients that are often taken care of by families and they prefer simplicity and straightforwardness, they kind of worry that if there's more pills, then somehow the patient is sicker. The third constituency that should not be ignored is the health care community. We don't like [administering drugs] multiple times a day, we don't like multiple pills a day. Across the board, this one tablet, once a day across therapeutic dose range is a win-win-win situation.

How does this decision differ from the February 2023 approval of the once-daily extended-release formulation?

The previous one tablet, once a day applied to only a few doses. At that time, we only had 6, 9, and 12 mg as opportunities. Now the portfolio is dramatically bigger. We now have therapeutic dose ranges of 24, 30, 36, 42, and 48 mg. Because of this new approval, we have one tablet, once a day as an opportunity. Besides the psychological impact, once a day, one tablet also is an administration advantage. There are no downsides, and all I can see are significant upside to this new approval by the FDA.

From a safety perspective, are there any notable concerns? Any drug-to-drug interactions clinicians should be aware of?

If you're switching from Austedo to Austedo XR, there is no need to cross taper, down titrate, up-titrate. You go from a dose to dose number. Secondly, pharmacokinetic-wise, the twice-a-day administration of Austedo and the once-a-day administration of Austedo XR are biosimilar. Besides what we already know about the safety drug-drug issues with the drug interaction issues with Austedo, there's nothing new to be added with Austedo XR. There are however, some additional advantages. Perhaps the biggest one is the food effect is no longer part of the label. Before, you had to take Austedo in a certain prescribed way after food, but for Austedo XR, you can give it both ways. You can imagine from a practical perspective how useful Austedo XR becomes to both the neurologist but also to the patient and their family.

Does the timing of when to administer the therapy impact its efficacy/outcomes?

No, the approval of Austedo XR is once-a-day. It doesn’t have to be prescribed specifically in the AM or afternoon or PM. As practicing clinicians, it is our job to fit the medication into the patient's needs. Being able to take Austedo XR anytime of the day is a big deal. The fact that the food effects are no longer a significant barrier further add to my thinking that Austedo XR is becoming a preferred way to treat our patients with either HD chorea or tardive dyskinesia.

Are there any major unmet needs for these patient populations we’re still working to handle?

Huntington disease is a challenge. It's literally a multi-headed monster. There isn't one challenge, we have a whole host of challenges. The mood aspects with HD, that's still a challenge to treat. The other big challenge, of course, is the progression of the illness. We don't really have disease modifying agents, but I also want to remind people that the chorea part of Huntington disease is a major destroyer of quality of life. Choking, falling, trouble speaking, these are huge robbers of the quality of life for these patients with Huntington quite unfortunately. Austedo XR could offer them the service of reducing the chorea form activities, which of course, then in turn, is expected to lead to downstream benefits. While we await the arrival of disease modifying agents, we really ought to celebrate the progress we keep making in the treatment of Huntington chorea. I predict that Austedo XR will become a very important ally of our patient when they're dealing with Huntington chorea.

Transcript edited for clarity.