Effective Date

Date of Origin   

07-01-2024           

01-01-2018

Cerdelga®

(eliglustat)

Capsule

Long-term treatment of adult patients with Gaucher disease type 1 who are CYP2D6 extensive metabolizers (EMs), intermediate metabolizers (IMs), or poor metabolizers (PMs) as detected by an FDA-cleared test for determining CYP2D6 genotype

Limitations of Use:

• CYP2D6 ultra-rapid metabolizers (URMs) may not achieve adequate concentrations of Cerdelga to achieve a therapeutic effect
• A specific dosage cannot be recommended for those patients whose CYP2D6 genotype cannot be determined (indeterminate metabolizers)

1

Opfolda™

(miglustat)

Capsule

Treatment of adult patients with late-onset Pompe disease (lysosomal acid alpha-glucosidase [GAA] deficiency) weighing greater than or equal to 40 kg and who are not improving on their current enzyme replacement therapy (ERT); Opfolda (an enzyme stabilizer) is indicated in combination with Pombiliti (a hydrolytic lysosomal glycogen-specific enzyme)

11

Zavesca®

(miglustat)*

Capsule

Monotherapy for treatment of adult patients with mild to moderate type 1 Gaucher disease for whom enzyme replacement therapy is not a therapeutic option (e.g., due to allergy, hypersensitivity, or poor venous access)

* Generic available

2

Gaucher Disease

Gaucher disease (GD), the most common of the lysosomal storage disorders (LSDs), is a rare autosomal recessive metabolic disorder affecting only 1 in 40,000 in the general United States population.(4,7) Mutations in the GBA (glucocerebrosidase) gene cause reduced activity of the lysosomal enzyme glucocerebrosidase (also known as acid beta-glucosidase), resulting in the accumulation of harmful quantities of the glycolipid glucocerebroside (also known as glucosylceramide, or GLC) and other related sphingolipids. This multisystemic accumulation of GLC in various tissues, especially in lysosomes of macrophages, compromises the bone marrow, spleen, and liver, and less often the lungs, skin, kidneys, and heart.(3,4,7,8,9,10)

GD is classified into 3 clinical types, distinguished by their clinical features, management, and prognosis. However, as with most genetic diseases, there is a continuum of clinical findings and overlap within and between types, resulting in identification of additional subtypes.(4,5,7,9) GD Type 1 (GD1) is distinguished from GD Types 2 (GD2) and 3 (GD3) by the lack of characteristic involvement of the central nervous system (CNS).(3,4,5,7,8) As such, it is also known as non-neuronopathic GD.(3,4,7) In the United States, Europe, and Israel, 90% of GD patients have GD1, with a high carrier frequency in the Ashkenazi-Jewish population.(3,4,5,7,8) Age of onset for GD1 is variable, with some patients presenting between 12 and 24 months of age and others having no clinical signs until late adulthood.(3,4,7) Manifestation in the first or second decades of life typically results in more aggressive and severe symptoms than those manifesting at a later stage of life.(7) Presentation of symptoms among patients with GD1 is variable. Splenomegaly is the most common symptom; hepatomegaly is also common, but the liver increases relatively less than the spleen. Other common presenting symptoms are anemia, thrombocytopenia, bone disease, and delayed growth.(3,4,5,7,8,10) 

GD2 is an acute neuronopathic form of GD characterized by early onset, typically in the first year after birth. Neurologic complications are extensive and severe, with limited psychomotor development. Death occurs within the first 2 years of life, usually due to respiratory failure.(3,5,7) GD3 is the subacute or chronic neuronopathic form, has later onset than GD2, and has slower disease progression with patients typically surviving to second or third decades of life. The distinction between GD2 and GD3 is difficult.(3,4)

A diagnosis of GD should be considered in patients with unexplained anemia and easy bruising, particularly if they have enlargement of the spleen and liver.(3) Definitive diagnosis of GD can be confirmed by the finding of reduced glucocerebrosidase activity in leukocytes, fibroblasts, or other nucleated cells.(3,4,5,7,9,10) This enzyme assay test is typically known as BGL (beta-glucosidase leukocyte), and a finding of 15% or less of mean normal glucocerebrosidase enzyme activity is indicative of GD.(4,5) If BGL results are not conclusive and/or further confirmatory testing is desired, genetic testing is an option. Identification of two pathogenic alleles in the GBA gene can also determine diagnosis of GD.(3,4,5,9) The presence of neurologic complications has critical implications for prognosis and treatment and should be determined as soon as possible after diagnosis. Neuronopathic symptoms indicative of GD2 and GD3 include bulbar signs (e.g., stridor, strabismus, swallowing difficulty), pyramidal signs (e.g., opisthotonus, head retroflexion, spasticity, trismus), oculomotor apraxia, tonic-clonic seizures, myoclonic epilepsy, dementia, and ataxia. If not already performed as part of the diagnostic process, baseline measurement of hemoglobin level, platelet count, liver volume, and spleen volume should be documented.(4,5,7,10)

When possible, management of a patient with GD should occur with a multidisciplinary team at a Comprehensive Gaucher Treatment Center(5) (list of facilities nationwide available at www.gaucherdisease.org. Goals of treatment are elimination or improvement of symptoms, prevention of irreversible complications, and improvement in overall health and quality of life. An additional goal in children is optimization of growth.(3,6,8) Currently, two different therapeutic approaches for the treatment of GD1 are used: enzyme replacement therapy (ERT) [Cerezyme (imiglucerase), VPRIV (velaglucerase alfa), Elelyso (taliglucerase alfa)] and substrate reduction therapy (SRT) [Cerdelga (eliglustat), Zavesca (miglustat)].(3,5,6,8,9) ERT, intravenously administered, targets macrophages and increases the breakdown of accumulated glycolipids.(8) SRT, orally administered, reduces the amount of synthesized GLC to a level that can be effectively cleared by the mutated enzyme’s residual activity.(5,6,8)

The decision to offer ERT or SRT in patients with GD1 is based upon disease severity and/or significant disease progression.(6,7,8,10) To begin treatment with ERT or SRT, clinically significant manifestations must be present. Thrombocytopenia of sufficient magnitude to justify initiation of treatment is defined by platelet counts less than 100,000 microliter, as well as symptomatic presentation of splenomegaly, anemia, bone disease, and/or delayed growth.(3,4,5,7,8,9)

Pompe Disease

Pompe disease, also known as acid maltase deficiency (AMD) or glycogen storage disease type II (GSDII), is an autosomal recessive disorder caused by mutations in the GAA gene for enzyme acid alpha-glucosidase (GAA).(12,13) Deficiency of lysosomal enzyme GAA leads to accumulation of glycogen in lysosomes and cytoplasm, resulting in tissue destruction.(13)

Infantile-onset Pompe disease (IOPD) is characterized by cardiomyopathy, severe generalized hypotonia, respiratory distress typically requiring ventilator support, and failure to thrive. Most patients with this form die within the first year or two of life without treatment. The juvenile-adult form (late onset Pompe disease [LOPD]) is characterized by skeletal myopathy, delayed gross-motor development, and respiratory insufficiency and/or failure.(12,13)

Diagnosis can be confirmed by demonstration of reduced acid alpha-glucosidase glycogen enzyme activity in dried blood spots or leukocytes (skin fibroblasts or skeletal muscle tissue are also options). GAA gene mutational analysis is the preferred test to confirm the diagnosis (with two pathogenic alleles), since it is routinely available, less invasive, and may help predict cross-reactive immunologic material (CRIM) status.(12,13,14) Prenatal diagnosis is possible by DNA analysis of cultured amniocytes or chorionic villus samples, if the mutation in the family is known.(13,14)

Guidelines note that a trial of ERT may be considered in patients who receive invasive ventilation support, if there are predefined outcomes which can be evaluated and which, if achieved, would improve the functional status of the patient. After one year, decisions regarding the continuation of ERT in patients receiving invasive ventilation support should be made on a case-by-case basis.(15,16)

Opfolda (miglustat) in combination with Pombiliti (an ERT; cipaglucosidase alfa) was approved by the FDA in September 2023 as a new treatment for adults with LOPD. Pombiliti provides an exogenous source of GAA, which exerts enzymatic activity in cleaving accumulating glycogen. Opfolda binds with, stabilizes, and reduces inactivation of Pombiliti in the blood after infusion.(11)

Efficacy - Gaucher Disease

Until the FDA approval of the SRT Cerdelga in 2014, ERT was the mainstay of therapy in patients with GD1. A 12-month phase 3, open-label, noninferiority study (ENCORE) in 106 adults (18 years of age and older) with GD1, stable after greater than or equal to 3 years of ERT with Cerezyme or VPRIV, found Cerdelga noninferior to Cerezyme in maintaining stability of four component domains (i.e., hemoglobin level, platelet count, liver volume, spleen volume). A 9-month randomized, double-blind, placebo-controlled study (ENGAGE) in 40 treatment-naïve GD1 patients 16 years of age and older, demonstrated that treatment with Cerdelga led to greater improvements in spleen and liver volume, platelet count, and hemoglobin level compared to placebo. These findings provided Cerdelga its designation as first-line or maintenance therapy in adult patients with GD1.(1,5,6,8) 

The SRT Zavesca, approved in 2003, is indicated only for GD1 patients for whom ERT is not an option (e.g., due to allergy, hypersensitivity, or poor venous access). Studies of Zavesca have demonstrated significant reductions from baseline in liver and spleen volume, and a non-significant increase from baseline in hemoglobin level and platelet count.(2,5,6) 

Efficacy - Pompe Disease

PROPEL was a randomized, double-blind, active-controlled, international, multi-center clinical trial (NCT#03729362) in patients greater than or equal to 18 years old diagnosed with late-onset Pompe disease (LOPD). Patients were randomized 2:1 to receive Pombiliti in combination with Opfolda, or a non-U.S.-approved alglucosidase alfa product with placebo every other week for 52 weeks. The efficacy population included a total of 123 patients of whom 95 (77%) had received prior treatment with U.S.-approved alglucosidase alfa or a non-U.S.-approved alglucosidase alfa product (ERT-experienced) and 28 (23%) were ERT-naïve. More than two thirds (n=64, 67%) of ERT-experienced patients had been on ERT treatment for more than 5 years prior to entering the trial (mean of 7.4 years). Demographics, baseline sitting forced vital capacity (FVC) (% predicted), and 6-minute walk distance (6MWD) were generally similar between the 2 treatment groups. Key efficacy endpoints included assessment of sitting FVC (% predicted) and 6MWD. The ERT-experienced patients treated with Pombiliti in combination with Opfolda showed a numerically favorable change in sitting FVC from baseline at Week 52 (p=0.006).(11)

Patients treated with combination Pombiliti and Opfolda walked on average 21 meters farther from baseline as compared to those treated with a non-U.S.-approved alglucosidase alfa product with placebo who walked 8 meters farther from baseline; the estimated treatment difference was 14 meters (95% CI: -1, 28). The ERT-experienced patients treated with Opfolda in combination with Pombiliti showed a numerically favorable change in 6MWD from baseline at Week 52 (p=0.047).(11)

Opfolda in combination with Pombiliti is not approved for use in ERT-naïve patients with LOPD. The ERT-naïve patient subgroup enrolled too few patients to conclusively interpret the data.(11)

A U.S.-approved alglucosidase alfa product was not used in this clinical trial. Conclusions cannot be drawn from this clinical trial regarding comparative effectiveness between a U.S.-approved alglucosidase alfa product and Opfolda in combination with Pombiliti for the treatment of adult patients with LOPD.(11)

Safety

Cerdelga (eliglustat) is contraindicated in the following patients based on CYP2D6 metabolizer status due to the risk of cardiac arrhythmias from prolongation of the PR, QTc, and/or QRS cardiac intervals:(1)

• Extensive metabolizers (EMs):
  • Taking a strong or moderate CYP2D6 inhibitor concomitantly with a strong or moderate CYP3A inhibitor
  • Moderate or severe hepatic impairment
  • Mild hepatic impairment taking a strong or moderate CYP2D6 inhibitor
• Intermediate metabolizers (IMs):
  • Taking a strong or moderate CYP2D6 inhibitor concomitantly with a strong or moderate CYP3A inhibitor
  • Taking a strong CYP3A inhibitor
  • Any degree of hepatic impairment
• Poor metabolizers (PMs):
  • Taking a strong CYP3A inhibitor
  • Any degree of hepatic impairment

Opfolda in combination with Pombiliti is contraindicated in pregnancy.(11)

Zavesca (miglustat) has no contraindications.(2)

1

Cerdelga prescribing information. Genzyme Corporation. December 2022.

2

Zavesca prescribing information. Actelion Pharmaceuticals US, Inc. August 2022.

3

National Organization for Rare Disorders (NORD) – Physicians Guides. Gaucher Disease. Last updated March 2020. Available at: https://rarediseases.org/physician-guide/gaucher-disease/.

4

Hughes D, Sidransky E, et al. Gaucher Disease: Pathogenesis, Clinical Manifestations, and Diagnosis. UpToDate. Last updated June 2022. Literature review current through December 2023.

5

Pastores GM, Hughes DA. Gaucher Disease. July 2000 [Updated December 2023]. In: Adam MP, Ardinger HH, Pago RA, et al. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2024. Available at: https://www.ncbi.nlm.nih.gov/books/NBK1269/.

6

Hughes D, Sidransky E, et al. Gaucher Disease: Treatment. UpToDate. Last updated August 2022. Literature review current through December 2023.

7

Martins AM, Valadares ER, Porta G, et al. Recommendations on Diagnosis, Treatment, and Monitoring for Gaucher Disease. J Pediatr. 2009;155(4):S10-S18.

8

Biegstraaten M, Cox TM, Belmatoug N, et al. Management Goals for Type 1 Gaucher Disease: An Expert Consensus Document from the European Working Group on Gaucher Disease. Blood Cells Mol Dis. 2018;68:203-208. 

9

Wang RY, Bodamer OA, Watson MS, et al. American College of Medical Genetics (ACMG) Work Group on Lysosomal Storage Diseases: Diagnostic Confirmation and Management of Presymptomatic Individuals. Genet Med. 2011 May;13(5):457-484.

10

Weinreb NJ, Aggio MC, Andersson HC, et al. Gaucher Disease Type 1: Revised Recommendations on Evaluations and Monitoring for Adult Patients. Semin Hematol. 2004;41(suppl 5):15-22.

11

Opfolda prescribing information. Amicus Therapeutics US, LLC. September 2023. 

12

Kronn DF, Day-Salvatore D, Hwu WL, et al. The Pompe Disease Newborn Screening Working Group on Management of Confirmed Newborn-Screened Patients with Pompe Disease Across the Disease Spectrum. J Pediatrics. 2017 Jul;140(1):S24-S45.

13

Hahn S, et al. Lysosomal Acid Alpha-Glucosidase Deficiency (Pompe Disease, Glycogen Storage Disease II, Acid Maltase Deficiency). UpToDate. Last updated November 2021. Literature review current through December 2023.

14

Reuser AJJ, et al. Pompe Disease. National Organization for Rare Disorders (NORD). Last updated January 2024. Available at: https://rarediseases.org/rare-diseases/pompe-disease/.

15

Cupler EJ, Berger KI, Leshner RT, et al. American Association of Neuromuscular and Electrodiagnostic Medicine (AANEM) Position Statement: Consensus Treatment Recommendations for Late-Onset Pompe Disease. Muscle Nerve. 2012 Mar;45(3):319-333.

16

Tarnopolsky M, Katzberg H, Petrof BJ, et al. Pompe Disease Diagnosis and Management: Evidence-Based Guidelines from a Canadian Expert Panel. Can J Neurol Sci. 2016;43:472-485.

Cerdelga

eliglustat tartrate cap

84 MG

M ; N ; O ; Y

N

Opfolda

miglustat (gaa deficiency) cap

65 MG

M ; N ; O ; Y

N

Yargesa ; Zavesca

miglustat cap

100 MG

M ; N ; O ; Y

O ; Y

Cerdelga

Eliglustat Tartrate Cap 84 MG (Base Equivalent)

84 MG

60

Capsules

30

DAYS

Opfolda

miglustat (gaa deficiency) cap

65 MG

8

Capsules

28

DAYS

Yargesa ; Zavesca

Miglustat Cap 100 MG

100 MG

90

Capsules

30

DAYS

Cerdelga

eliglustat tartrate cap

84 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Opfolda

miglustat (gaa deficiency) cap

65 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Yargesa ; Zavesca

miglustat cap

100 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Cerdelga

Eliglustat Tartrate Cap 84 MG (Base Equivalent)

84 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Opfolda

miglustat (gaa deficiency) cap

65 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Yargesa ; Zavesca

Miglustat Cap 100 MG

100 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Cerdelga, Zavesca

Initial Evaluation

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

1. ONE of the following:
   1. The requested agent is eligible for continuation of therapy AND BOTH of the following:

1. ONE of the following: 
   1. The patient has been treated with the requested agent (starting on samples is not approvable) within the past 90 days OR
   2. The prescriber states the patient has been treated with the requested agent (starting on samples is not approvable) within the past 90 days AND is at risk if therapy is changed AND
2. The prescriber has assessed current status of the following: spleen volume, hemoglobin level, liver volume, platelet count, growth, bone pain or crisis OR
3. ALL of the following:
   1. The patient has a diagnosis of Gaucher disease type 1 (GD1) AND
   2. ONE of the following:
      1. The patient has baseline (prior to therapy for the requested indication) glucocerebrosidase enzyme activity of less than or equal to 15% of mean normal in fibroblasts, leukocytes, or other nucleated cells OR
      2. Genetic analysis confirmed two (2) pathogenic alleles in the glucocerebrosidase (GBA) gene AND
   3. 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. There is support for using the requested agent for the patient’s age for the requested indication AND
   4. The patient does NOT have any neuronopathic symptoms indicative of Gaucher disease type 2 or type 3 [e.g., bulbar signs (e.g., stridor, strabismus, swallowing difficulty), pyramidal signs (e.g., opisthotonos, head retroflexion, spasticity, trismus), oculomotor apraxia, tonic-clonic seizures, myoclonic epilepsy, dementia, ataxia] AND
   5. The prescriber has assessed baseline (prior to therapy for the requested indication) status of hemoglobin level, platelet count, liver volume, and spleen volume AND
   6. The patient has at least ONE of the following clinical presentations at baseline (prior to therapy for the requested indication):
      1. Anemia defined as mean hemoglobin (Hb) level below the testing laboratory’s lower limit of the normal range based on age and gender OR
      2. Thrombocytopenia (platelet count less than 100,000/microliter on at least 2 measurements) OR
      3. Hepatomegaly OR
      4. Splenomegaly OR
      5. Growth failure (i.e., growth velocity is below the standard mean for age) OR
      6. Evidence of bone disease with other causes ruled out AND
   7. If the requested agent is Zavesca or miglustat, enzyme replacement therapy (ERT) is NOT a therapeutic option (e.g., due to allergy, hypersensitivity, poor venous access, previous ERT failure) AND
4. If the requested agent is Cerdelga or eliglustat, the patient is a CYP2D6 extensive metabolizer (EM), intermediate metabolizer (IM), or poor metabolizer (PM), as detected by an FDA-cleared test for determining CYP2D6 genotype AND
5. If the request is for one of the following brand agents with an available generic equivalent (listed below), then ONE of the following:
   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. There is support for the use of the requested brand agent over the generic equivalent AND

4. The prescriber is a specialist in the area of the patient’s diagnosis (e.g., endocrinologist, geneticist) or the prescriber has consulted with a specialist in the area of the patient’s diagnosis AND
5. The patient will NOT be using the requested agent in combination with another substrate reduction therapy agent (e.g., Cerdelga, Opfolda, Zavesca) for the requested indication AND
6. The patient does NOT have any FDA labeled contraindications to the requested agent

Length of Approval:  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:

1. The patient has been previously approved for the requested agent through the plan’s Prior Authorization process [Note: patients not previously approved for the requested agent will require initial evaluation review] AND
2. The patient has had improvements or stabilization with the requested agent as indicated by ONE of the following:
   1. Spleen volume OR
   2. Hemoglobin level OR
   3. Liver volume OR
   4. Platelet count (sufficient to decrease the risk of bleeding) OR
   5. Growth OR
   6. Bone pain or crisis AND
3. If the request is for one of the following brand agents with an available generic equivalent (listed below), then ONE of the following:
   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. There is support for the use of the requested brand agent over the generic equivalent AND

4. The prescriber is a specialist in the area of the patient’s diagnosis (e.g., endocrinologist, geneticist) or the prescriber has consulted with a specialist in the area of patient’s diagnosis AND
5. The patient will NOT be using the requested agent in combination with another substrate reduction therapy agent (e.g., Cerdelga, Opfolda, Zavesca) for the requested indication AND
6. The patient does NOT have any FDA labeled contraindications to the requested agent

Length of Approval:  12 months

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

Opfolda

Initial Evaluation

Opfolda will be approved when ALL of the following are met:

1. ONE of the following:
   1. The requested agent is eligible for continuation of therapy AND ONE of the following:

1. The patient has been treated with the requested agent (starting on samples is not approvable) within the past 90 days OR
2. The prescriber states the patient has been treated with the requested agent (starting on samples is not approvable) within the past 90 days AND is at risk if therapy is changed OR
3. ALL of the following:
   1. The patient has a diagnosis of late-onset Pompe disease (acid maltase deficiency [AMD]; glycogen storage disease type II [GSDII]) confirmed by at least ONE of the following:
      1. Genetic analysis confirms biallelic mutation (two pathogenic variants) in the GAA gene OR
      2. The patient has deficient acid alpha-glucosidase glycogen enzyme activity in dried blood spots, leukocytes, skin fibroblasts, and/or skeletal muscle tissue AND
   2. The patient is not improving on their current enzyme replacement therapy (ERT) AND
   3. The requested agent will be taken in combination with Pombiliti AND
   4. 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. There is support for using the requested agent for the patient’s age for the requested indication AND
4. The prescriber has assessed current status of the following: gross motor function (e.g., walking distance), pulmonary function (e.g., forced vital capacity [FVC]) AND
5. The prescriber is a specialist in the area of the patient’s diagnosis (e.g., endocrinologist, geneticist) or the prescriber has consulted with a specialist in the area of the patient’s diagnosis AND
6. The patient does NOT have any FDA labeled contraindications to the requested agent 

Length of Approval:  12 months

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

Renewal Evaluation

Opfolda will be approved when ALL of the following are met:

1. The patient has been previously approved for the requested agent through the plan’s Prior Authorization process [Note: patients not previously approved for the requested agent will require initial evaluation review] AND
2. The patient has had improvements or stabilization with the requested agent as indicated by ONE of the following:
   1. Gross motor function (e.g., walking distance) OR
   2. Pulmonary function (e.g., forced vital capacity [FVC]) AND
3. The prescriber is a specialist in the area of the patient’s diagnosis (e.g., endocrinologist, geneticist) or the prescriber has consulted with a specialist in the area of the patient’s diagnosis AND
4. The patient does NOT have any FDA labeled contraindications to the requested agent

Length of Approval:  12 months

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

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

1. The requested quantity (dose) does NOT exceed the program quantity limit OR
2. 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
3. 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. There is support of therapy with a higher dose for the requested indication

Length of Approval:  up to 12 months