–Evidence suggests drugs offer short-term benefits but are vastly overpriced, leading to “low value” designation and triggering ICER’s Affordability and Access Alert–

BOSTON, December 21, 2017-The Institute for Clinical and Economic Review today released a Final Evidence Report and Report-at-a-Glance on vesicular monoamine transporter 2 (VMAT2) inhibitors for management of tardive dyskinesia (TD). TD is a repetitive, involuntary movement disorder caused by prolonged use of certain medications, most commonly antipsychotic drugs used to treat schizophrenia and affective disorders. The report reviews evidence on the comparative clinical effectiveness and value of valbenazine (Ingrezza®, Neurocrine Biosciences, Inc.), deutetrabenazine (Austedo®, Teva), and tetrabenazine (Xenazine®, Lundbeck and multiple generics).

Both valbenazine and deutetrabenazine were approved earlier this year for treatment of TD; tetrabenazine was approved in 2008 for use in Huntington’s disease, a rare condition, and has been used to treat TD despite lacking a formal indication for the disorder. Although TD is far more prevalent than Huntington’s disease, the announced list prices of both valbenazine and deutetrabenazine are similar to tetrabenazine’s rare-disease price.

ICER’s report was reviewed at a public meeting of the New England Comparative Effectiveness Public Advisory Council (New England CEPAC), where a majority of the Council voted that evidence suggests a net health benefit of both valbenazine and deutetrabenazine in treating TD. Uncertainty remains, however, around the long-term benefits and harms of the drugs, and the costs of the newly approved agents are extremely high. The Council found evidence insufficient to distinguish between the net benefit of valbenazine and deutetrabenazine, or to demonstrate a net health benefit of tetrabenazine.

“While more research is needed to understand the long-term benefits and harms of VMAT2 inhibitors, these drugs represent an important step forward for patients living with tardive dyskinesia,” noted Dan Ollendorf, PhD, ICER’s Chief Scientific Officer. “Unfortunately, applying a rare-disease pricing strategy to therapies used to treat a much more common, chronic condition creates unsustainable financial barriers for patients and the health care system. Manufacturers and payers must collaborate to develop strategies that allow access to these therapies for those who most need them, without straining health care budgets or passing high costs on to patients.”

Affordability & Access Alert

ICER is issuing an Affordability and Access Alert as part of its final report on VMAT2 inhibitors for treating TD. Assuming standard discounts, only one in five eligible Americans with TD could be treated with the new therapies before crossing ICER’s budget threshold of $915 million per year.

Policy Recommendations

Following the voting session during the New England CEPAC meeting, a policy roundtable of experts including patient advocates, physicians, representatives of the makers of the drugs under review, and payer representatives convened to discuss the implications of the evidence for policy and practice. Key recommendations stemming from the roundtable discussion include:

  • In order to provide reasonable value and thereby facilitate improved access and affordability for patients, manufacturers should reduce prices for the VMAT2 inhibitors to better align with their demonstrated short-term clinical benefits.
  • Given that the new VMAT2 inhibitors are priced far beyond their relative benefits for patients, payers should use available evidence, along with patient and clinical expert input, to develop prior authorization criteria, periods of authorized treatment, and methods for feedback to clinicians regarding the potential for alternative management of TD (e.g., switching from an offending DRBA to another agent). 
  • Regulators should require post-approval, long-term comparative outcomes studies for treatments initially evaluated and approved in very short-term randomized trials, but for which long-term therapy would be expected.
  • Professional societies should accept the responsibility to update their clinical practice guidelines rapidly following the advent of paradigm-changing treatment options like the VMAT2 inhibitors.
  • Patients and patient representatives should advocate for inclusion of new outcome measures in clinical trials that better document the impact of TD on work, family, and social interactions.
Additional policy recommendations are available in more detail in ICER’s Final Report.