Researchers Review Benefits, Shortcomings of Valbenazine, Deutetrabenazine for TD

Steven J. Atlas, MD, MPH

In recent time, US Food and Drug Administration (FDA) approved 2 medicines to treat tardive dyskinesia (TD)—valbenazine and deutetrabenazine.

These approvals, while the groundbreaking in the once-vacant market, came in spite of data driven by short-term trials and expensive drug costs, according to an evidence report compiled by the Institute for Clinical and Economic Review (ICER).

Researchers from Boston completed the report in order to support the New England Comparative Effectiveness Public Advisory Council, which convened to discuss valbenazine and deutetrabenazine.

ICER assessed the comparative clinical effectiveness, cost-effectiveness, and potential budget impact of the pair of approved vesicular monoamine transporter 2 (VMAT2) inhibitors—as well as tetrabenazine, in adults with TD. Tetrabenazine, though approved by the FDA for the treatment of Huntington’s disease, was included in the study because it is sometimes used as an off-label treatment for TD.

The observed patients’ TD was required to occur for at least 3 months and they needed to have a history of dopamine-receptor blocking agents to be included in the evaluation. The ICER investigators found 2 placebo-controlled valbenazine studies that followed patients for 6 weeks, and a pair of placebo-controlled deutetrebenazine trials that followed patients for 12 weeks.

At the end of each of the studies, patients were evaluated based on the Abnormal Involuntary Movement Scale (AIMS) and an expert looking at tapes of the patients.

AIMS ratings did change, though it may not be clinically different, the report authors wrote. When the patients evaluated themselves, there also seemed to be overall improvement. The ICER team determined that the trials were “good or fair quality and of relatively short duration.”

They also noted that there were no trials that compared VMAT2 inhibitors to each other.

The researchers also found a phase 3 trial which showed that 80 mg and 40 mg valbenazine statistically significantly improved AIMS score improvements compared to a placebo. Along those same lines, patients who received 36 mg and 24 mg of deutetrabenazine showed greater improvement in AIMS scores compared to a placebo. Some side effects of valbenazine and deutetrabenazine included drowsiness, fatigue, headaches, and akathisia, according to the researchers.

In terms of cost-effectiveness, the researchers found that for lifetime use of either valbenazine or deutetrabenazine represented increased cost and increased quality-adjusted life years compared to placebo treatment. Over a lifetime, valbenazine and deutetrabenazine use in cost-effective ways topped out at about $752,000 and $1.101 million, respectively.

When the researchers extrapolated the data to estimate a population of 360,000 adults with moderate to severe TD using these drugs over a five-year time period, the total potential budget impact was about $22.5 billion, or $4.5 billion annually.

Study author Steven J. Atlas, MD, MPH, told MD Mag that until the VMAT2 inhibitors reached the market, clinicians were limited by TD therapy options.

“This is encouraging, but the piece highlights the limited data from short-term trials and the very high cost of these medicines,” Atlas said. “The importance long-term comparative data is because if helpful, these medicines will need to be used chronically to control the tardive dyskinesia symptoms.”

The study, “Effectiveness and Value of 2 Novel Treatments for Tardive Dyskinesia,” was published in JAMA Internal Medicine.