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ph-1152

Vesicular Monoamine Transporter 2 (VMAT2) Inhibitors Prior Authorization with Quantity Limit Program Summary

Policy Number: PH-1152

This program applies to Blue Partner, Commercial, GenPlus, NetResults A series, SourceRx and Health Insurance Marketplace formularies.

POLICY REVIEW CYCLE

Effective Date	Date of Origin
04-01-2024	10-01-2021

FDA APPROVED INDICATIONS AND DOSAGE

Agent(s)	FDA Indication(s)	Notes	Ref#
Austedo® (deutetrabenazine) Tablet	Treatment of adults with chorea associated with Huntington’s disease Treatment of adults with tardive dyskinesia		1
Austedo XR® (deutetrabenazine er) Tablet	Treatment of adults with chorea associated with Huntington’s disease Treatment of adults with tardive dyskinesia		8
Ingrezza® (valbenazine) Capsule	Treatment of adults with tardive dyskinesia Treatment of adults with chorea associated with Huntington's disease		2
Xenazine® (tetrabenazine) Tablet	Treatment of chorea associated with Huntington’s disease	*generic available	3

See package insert for FDA prescribing information: https://dailymed.nlm.nih.gov/dailymed/index.cfm

CLINICAL RATIONALE

Huntington's Disease

Huntington’s Disease (HD) is a hereditary neurodegenerative disorder caused by an expansion of a repeating cytosine-adenine-guanine (CAG) triplet series in the HTT (huntingtin) gene on chromosome 4. It is inherited in an autosomal dominant pattern with each child of an affected parent having a 50% chance of developing the disease. There is currently no cure or treatment which can halt, slow, or reverse the progression of the disease. The average length of survival after clinical diagnosis is typically 10-20 years.(6)

Huntington’s Disease manifests as a triad of motor, cognitive, and psychiatric disorders that begin gradually and progress over many years. These disorders of HD cannot be considered in isolation with disabilities in one area leading to problems in another area. The cognitive disorder is characterized by a reduction of speed and flexibility of mental processing. The psychiatric disorder is less predictable. People may suffer from depression, mania, obsessive compulsive disorder and various forms of psychosis. Almost all people with HD will experience disease-specific personality and behavioral changes that result in severe consequences to their marital, social, and economic well-being. The movement disorder includes emergence of involuntary movements (chorea) and the impairment of voluntary movements which results in reduced manual dexterity, slurred speech, swallowing difficulties, problems with balance, and falls. The most recognized motor symptom is chorea, and the clinical diagnosis of Huntington's Disease traditionally is based on the observation of this symptom. More than 90% of people affected by HD have chorea, which is characterized by involuntary movements that are often sudden, irregular, and purposeless. The movements are often more prominent in the extremities early in the disease, but may eventually include facial grimacing, eyelid elevation, neck, shoulder, trunk, and leg movements as the disease progresses. Chorea typically increases in frequency and amplitude over time and may peak about 10 years after disease onset.(6)

Treating chorea is an important part of HD management and should be considered if chorea causes the patient distress or discomfort. Vesicular monoamine transporter 2 (VMAT 2) inhibitors are FDA labeled agents for treatment and are considered first-line treatment unless the patient suffers from not well-managed depression or suicidal thoughts.(4) The precise mechanism of action is unknown, but VMAT2 inhibitors are believed to exert their anti-chorea effects as a reversible depletor of monoamines (such as dopamine, serotonin, norepinephrine, and histamine) from nerve terminals. They reversibly inhibit VMAT2, a transporter that regulates monoamine uptake from the cytoplasm to the synaptic vesicle resulting in decreased uptake of monoamines and depletion of monoamine stores. (1-3,8)

Tardive dyskinesia

Tardive syndromes are persistent abnormal involuntary movement disorders caused by sustained exposure to antipsychotic medication, the most common of which are tardive dyskinesia, tardive dystonia, and tardive akathisia. They begin later in treatment than acute dystonia, akathisia, or medication-induced parkinsonism and they persist and may even increase, despite reduction in dose or discontinuation of the antipsychotic medication. Tardive dyskinesia has been reported after exposure to any of the available antipsychotic medications. It occurs at a rate of approximately 4-8% per year in adult patients treated with first generation antipsychotics. Evaluation of the risk of tardive dyskinesia is complicated by the fact that dyskinetic movements may be observed with a reduction in antipsychotic medication dose. Fluctuations in symptoms are also common and may be influenced by factors such as psychosocial stressors. Regular assessment of patients for tardive syndromes through clinical examination or through the use of a structured evaluative tool, such as the Abnormal Involuntary Movement Scale (AIMS), can aid in identification, clarifying the likely etiology, monitoring, and determining the effects of medication changes or treatments for tardive dyskinesia. It should be noted that there is no specific score threshold that suggests a need for intervention, although ranges of scores are noted to correspond with mild, moderate, and severe symptoms. If no other contributing etiology is identified and moderate to severe or disabling tardive dyskinesia persists, treatment with a VMAT2 inhibitor is recommended. A change in antipsychotic therapy to a lower potency medication and particularly to clozapine may be associated with a reduction in tardive dyskinesia. The potential benefits of changing medication should be considered in light of the possibility of symptom recurrence.(7)

Safety

VMAT2 inhibitors (including Austedo/Austedo XR, Ingrezza, and Xenazine) have a boxed warning due to an increased risk of depression and suicidal thoughts and behavior in patients with Huntington’s disease. Anyone considering the use of VMAT2 inhibitors (including Austedo/Austedo XR, Ingrezza, and Xenazine) must balance the risks of depression and suicidal ideation and behavior with the clinical need for treatment of chorea. Closely monitor patients for the emergence or worsening of depression, suicidal ideation, or unusual changes in behavior. Inform patients, their caregivers, and families of the risk of depression and suicidal ideation and behavior and instruct them to report behaviors of concern promptly to the treating physician. Particular caution should be exercised in treating patients with a history of depression or prior suicide attempts or ideation, which are increased in frequency in patients with Huntington’s disease.(1-3,8)

Austedo/Austedo XR are contraindicated in patients:(1,8)

with Huntington’s disease who are suicidal, or have untreated or inadequately treated depression
with hepatic impairment
taking reserpine. At least 20 days should elapse after stopping reserpine before starting Austedo/Austedo XR.
taking monoamine oxidase inhibitors (MAOIs). Austedo/Austedo XR should not be used in combination with an MAOI, or within 14 days of discontinuing therapy with an MAOI.
taking tetrabenazine or valbenazine

Ingrezza is contraindicated in patients with a history of hypersensitivity to valbenazine or any components of Ingrezza. Rash, urticaria, and reactions consistent with angioedema (e.g., swelling of the face, lips, and mouth) have been reported.(2)

Xenazine is contraindicated in patients:(3)

who are actively suicidal, or in patients with untreated or inadequately treated depression
with hepatic impairment
taking monoamine oxidase inhibitors (MAOIs). Tetrabenazine should not be used in combination with an MAOI, or within a minimum of 14 days of discontinuing therapy with an MAOI.
taking reserpine. At least 20 days should elapse after stopping reserpine before starting Xenazine.
taking deutetrabenazine or valbenazine

REFERENCES

Number	Reference
1	Austedo prescribing information. Teva Neuroscience, Inc. February 2023.
2	Ingrezza prescribing information. Neurocrine Biosciences, Inc. August 2023.
3	Xenazine Prescribing Information. Bausch Health Companies, Inc. November 2019.
4	Bachoud-Lévi, A.-C., Ferreira, J., Massart, R., Youssov, K., Rosser, A., Busse, M., Craufurd, D., Reilmann, R., De Michele, G., Rae, D., Squitieri, F., Seppi, K., Perrine, C., Scherer-Gagou, C., Audrey, O., Verny, C., & Burgunder, J.-M. (2019). International Guidelines for the Treatment of Huntington’s Disease. Frontiers in Neurology, 10(710). https://doi.org/10.3389/fneur.2019.00710
5	Reference no longer used
6	Nance, M., Paulsen, J., Rosenblatt, A., & Wheelock, V. (2011). A Physician’s Guide to the Management of Huntington’s Disease (3rd edition). Huntington’s Disease Society of America. https://hdsa.org/wp-content/uploads/2015/03/PhysiciansGuide_3rd-Edition.pdf
7	Keepers, G. A., Fochtmann, L. J., Anzia, J. M., Benjamin, S., Lyness, J. M., Mojtabai, R., Servis, M., Walaszek, A., Buckley, P., Lenzenweger, M. F., Young, A. S., Degenhardt, A., & Hong, S.-H. (2020). The American Psychiatric Association Practice Guideline for the Treatment of Patients with Schizophrenia. American Journal of Psychiatry, 177(9), 868–872. https://doi.org/10.1176/appi.ajp.2020.177901
8	Austedo XR prescribing information. Teva Neuroscience, Inc. February 2023.

POLICY AGENT SUMMARY PRIOR AUTHORIZATION

Target Brand Agent(s)	Target Generic Agent(s)	Strength	Targeted MSC	Available MSC	Final Age Limit	Preferred Status

Austedo ; Austedo patient titration ; Austedo xr ; Austedo xr patient titrat	deutetrabenazine tab ; deutetrabenazine tab er ; deutetrabenazine tab er titration pack ; deutetrabenazine tab titration pack	12 MG ; 24 MG ; 6 & 12 & 24 MG ; 6 & 9 & 12 MG ; 6 MG ; 9 MG	M ; N ; O ; Y	N
Xenazine	tetrabenazine tab	12.5 MG ; 25 MG	M ; N ; O ; Y	O ; Y
Ingrezza	valbenazine tosylate cap ; valbenazine tosylate cap therapy pack	40 & 80 MG ; 40 MG ; 60 MG ; 80 MG	M ; N ; O ; Y	N

POLICY AGENT SUMMARY QUANTITY LIMIT

Target Brand Agent Name(s)	Target Generic Agent Name(s)	Strength	QL Amount	Dose Form	Day Supply	Duration	Addtl QL Info	Allowed Exceptions	Targeted NDCs When Exclusions Exist

Austedo	Deutetrabenazine Tab 12 MG	12 MG	120	Tablets	30	DAYS
Austedo	Deutetrabenazine Tab 6 MG	6 MG	60	Tablets	30	DAYS
Austedo	Deutetrabenazine Tab 9 MG	9 MG	120	Tablets	30	DAYS
Austedo xr	deutetrabenazine tab er	6 MG	30	Tablets	30	DAYS
Austedo xr	deutetrabenazine tab er	12 MG	30	Tablets	30	DAYS
Austedo xr	deutetrabenazine tab er	24 MG	60	Tablets	30	DAYS
Austedo xr patient titrat	deutetrabenazine tab er titration pack	6 & 12 & 24 MG	42	Tablets	180	DAYS
Ingrezza	Valbenazine Tosylate Cap	60 MG	30	Capsules	30	DAYS
Ingrezza	Valbenazine Tosylate Cap 40 MG (Base Equiv)	40 MG	30	Capsules	30	DAYS
Ingrezza	Valbenazine Tosylate Cap 80 MG (Base Equiv)	80 MG	30	Capsules	30	DAYS
Ingrezza	Valbenazine Tosylate Cap Therapy Pack 40 MG (7) & 80 MG (21)	40 & 80 MG	28	Capsules	180	DAYS
Xenazine	Tetrabenazine Tab 12.5 MG	12.5 MG	240	Tablets	30	DAYS
Xenazine	Tetrabenazine Tab 25 MG	25 MG	120	Tablets	30	DAYS

CLIENT SUMMARY – PRIOR AUTHORIZATION

Target Brand Agent Name(s)	Target Generic Agent Name(s)	Strength	Client Formulary
Austedo ; Austedo patient titration ; Austedo xr ; Austedo xr patient titrat	deutetrabenazine tab ; deutetrabenazine tab er ; deutetrabenazine tab er titration pack ; deutetrabenazine tab titration pack	12 MG ; 24 MG ; 6 & 12 & 24 MG ; 6 & 9 & 12 MG ; 6 MG ; 9 MG	Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx
Ingrezza	valbenazine tosylate cap ; valbenazine tosylate cap therapy pack	40 & 80 MG ; 40 MG ; 60 MG ; 80 MG	Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx
Xenazine	tetrabenazine tab	12.5 MG ; 25 MG	Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

CLIENT SUMMARY – QUANTITY LIMITS

Target Brand Agent Name(s)	Target Generic Agent Name(s)	Strength	Client Formulary
Austedo	Deutetrabenazine Tab 12 MG	12 MG	Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx
Austedo	Deutetrabenazine Tab 6 MG	6 MG	Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx
Austedo	Deutetrabenazine Tab 9 MG	9 MG	Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx
Austedo xr	deutetrabenazine tab er	6 MG	Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx
Austedo xr	deutetrabenazine tab er	24 MG	Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx
Austedo xr	deutetrabenazine tab er	12 MG	Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx
Austedo xr patient titrat	deutetrabenazine tab er titration pack	6 & 12 & 24 MG	Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx
Ingrezza	Valbenazine Tosylate Cap	60 MG	Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx
Ingrezza	Valbenazine Tosylate Cap 40 MG (Base Equiv)	40 MG	Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx
Ingrezza	Valbenazine Tosylate Cap 80 MG (Base Equiv)	80 MG	Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx
Ingrezza	Valbenazine Tosylate Cap Therapy Pack 40 MG (7) & 80 MG (21)	40 & 80 MG	Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx
Xenazine	Tetrabenazine Tab 12.5 MG	12.5 MG	Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx
Xenazine	Tetrabenazine Tab 25 MG	25 MG	Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

PRIOR AUTHORIZATION CLINICAL CRITERIA FOR APPROVAL

Module

Clinical Criteria for Approval

Initial Evaluation

Target Agent(s) will be approved when ALL of the following are met:

ONE of the following:
1. The requested agent is Austedo/deutetrabenazine, Austedo XR/deutetrabenazine ER, or Ingrezza/valbenazine AND ONE of the following:
  1. The patient has a diagnosis of tardive dyskinesia AND BOTH of the following:
    1. ONE of the following:
      1. The prescriber has reduced the dose or discontinued any medications known to cause tardive dyskinesia (i.e., dopamine receptor blocking agents) OR
      2. The prescriber has provided clinical rationale indicating that a reduced dose or discontinuation of any medications known to cause tardive dyskinesia is not appropriate AND
    2. The prescriber has documented the patient’s baseline Abnormal Involuntary Movement Scale (AIMS) score OR
  2. The patient has a diagnosis of chorea associated with Huntington’s disease OR
  3. The patient has another FDA approved indication for the requested agent OR
  4. The patient has another indication that is supported in compendia for the requested agent OR
2. The requested agent is Xenazine/tetrabenazine and ONE of the following:
  1. The patient has a diagnosis of chorea associated with Huntington’s disease OR
  2. The patient has another FDA approved indication for the requested agent OR
  3. The patient has another indication that is supported in compendia for the requested agent AND
If the request is for one of the following brand agents with an available generic equivalent (listed below), then ONE of the following:

Brand	Generic Equivalent
Xenazine	tetrabenazine

1. The patient has an intolerance or hypersensitivity to the generic equivalent that is not expected to occur with the brand agent OR
2. The patient has an FDA labeled contraindication to the generic equivalent that is not expected to occur with the brand agent OR
3. The prescriber has provided information to support the use of the requested brand agent over the generic equivalent AND
If the patient has an FDA labeled indication, then ONE of the following:
1. The patient’s age is within FDA labeling for the requested indication for the requested agent OR
2. The prescriber has provided information in support of using the requested agent for the patient’s age for the requested indication AND
The prescriber is a specialist in the area of the patient’s diagnosis (e.g., psychiatrist, neurologist), or the prescriber has consulted with a specialist in the area of the patient’s diagnosis AND
The patient will NOT be using the requested agent in combination with another agent included in this Prior Authorization program AND
The patient does NOT have any FDA labeled contraindications to the requested agent

Compendia Allowed: AHFS, or DrugDex 1 or 2a level of evidence

Length of Approval: Tardive dyskinesia - 3 months, all other indications - 12 months

NOTE: If Quantity Limit applies, please refer to Quantity Limit Criteria.

*Step therapy requirement may not apply if a prior health plan paid for the medication - documentation of a paid claim may be required.

Renewal Evaluation

Target Agent(s) will be approved when ALL of the following are met:

The patient has been previously approved for the requested agent through the plan’s Prior Authorization process AND
The prescriber is a specialist in the area of the patient’s diagnosis (e.g., psychiatrist, neurologist), or the prescriber has consulted with a specialist in the area of the patient’s diagnosis AND
ONE of the following:
1. The patient has a diagnosis of tardive dyskinesia AND has had improvements or stabilization from baseline in their Abnormal Involuntary Movement Scale (AIMS) score OR
2. The patient has a diagnosis other than tardive dyskinesia AND has had clinical benefit with the requested agent AND
If the request is for one of the following brand agents with an available generic equivalent (listed below), then ONE of the following:

Brand	Generic Equivalent
Xenazine	tetrabenazine

1. The patient has an intolerance or hypersensitivity to the generic equivalent that is not expected to occur with the brand agent OR
2. The patient has an FDA labeled contraindication to the generic equivalent that is not expected to occur with the brand agent OR
3. The prescriber has provided information to support the use of the requested brand agent over the generic equivalent AND
The patient will NOT be using the requested agent in combination with another agent included in this Prior Authorization program AND
The patient does NOT have any FDA labeled contraindications to the requested agent

Compendia Allowed: AHFS, or DrugDex 1 or 2a level of evidence

Length of Approval: 12 months

NOTE: If Quantity Limit applies, please refer to Quantity Limit Criteria.

QUANTITY LIMIT CLINICAL CRITERIA FOR APPROVAL

Module

Clinical Criteria for Approval

QL with PA

Quantity Limit for the Target Agent(s) will be approved when ONE of the following is met:

The requested quantity (dose) does NOT exceed the program quantity limit OR
ALL of the following:
1. The requested quantity (dose) exceeds the program quantity limit AND
2. The requested quantity (dose) does NOT exceed the maximum FDA labeled dose for the requested indication AND
3. The requested quantity (dose) cannot be achieved with a lower quantity of a higher strength that does not exceed the program quantity limit OR
ALL of the following:
1. The requested quantity (dose) exceeds the program quantity limit AND
2. The requested quantity (dose) exceeds the maximum FDA labeled dose for the requested indication AND
3. The prescriber has provided information in support of therapy with a higher dose for the requested indication

Length of Approval: Initial: tardive dyskinesia - 3 months, all other indications - 12 months

Renewal: 12 months

This pharmacy policy is not an authorization, certification, explanation of benefits or a contract. Eligibility and benefits are determined on a case-by-case basis according to the terms of the member’s plan in effect as of the date services are rendered. All pharmacy policies are based on (i) information in FDA approved package inserts (and black box warning, alerts, or other information disseminated by the FDA as applicable); (ii) research of current medical and pharmacy literature; and/or (iii) review of common medical practices in the treatment and diagnosis of disease as of the date hereof. Physicians and other providers are solely responsible for all aspects of medical care and treatment, including the type, quality, and levels of care and treatment.

The purpose of Blue Cross and Blue Shield of Alabama’s pharmacy policies are to provide a guide to coverage. Pharmacy policies are not intended to dictate to physicians how to practice medicine. Physicians should exercise their medical judgment in providing the care they feel is most appropriate for their patients.

Neither this policy, nor the successful adjudication of a pharmacy claim, is guarantee of payment.

Commercial _ CSReg _ VMAT2_Inhibitors_PAQL _ProgSum_ 04-01-2024