Oral PAH – Net Results Formulary

Restricted Product(s): brand and generic formulations

• Adcirca® (Tadalafil)
• Adempas® (Riociguat)
• Letairis® (Ambrisentan)
• Opsumit® (Macitentan)
• Orenitram® (Treprostinil)
• Revatio® (Sildenafil)
• Tracleer® (Bosentan)
• Uptravi® (Selexipag)

FDA Approved Use:

• Adcirca
  • For the treatment of pulmonary arterial hypertension (PAH) (WHO Group 1) to improve exercise ability.
• Adempas
  • For persistent/recurrent Chronic Thromboembolic Pulmonary Hypertension (CTEPH) (WHO Group 4) after surgical treatment or inoperable CTEPH to improve exercise capacity and WHO functional class.
  • For Pulmonary Arterial Hypertension (PAH) (WHO Group 1) to improve exercise capacity, improve WHO functional class and to delay clinical worsening.
• Letairis
  • For the treatment of pulmonary arterial hypertension (PAH) (WHO Group 1):
    • To improve exercise ability and delay clinical worsening.
    • ▪ In combination with tadalafil to reduce the risks of disease progression and hospitalization for worsening PAH, and to improve exercise ability.
• Opsumit
  • For the treatment of pulmonary arterial hypertension (PAH, WHO Group I) to delay disease progression. Disease progression included: death, initiation of intravenous (IV) or subcutaneous prostanoids, or clinical worsening of PAH (decreased 6-minute walk distance, worsened PAH symptoms and need for additional PAH treatment). OPSUMIT also reduced hospitalization for PAH.
• Orenitram
  • For the treatment of pulmonary arterial hypertension (PAH) (WHO Group 1) to improve exercise capacity.
• Revatio
  • For the treatment of pulmonary arterial hypertension (PAH) (WHO Group I) in adults to improve exercise ability and delay clinical worsening. Limitation of Use: Adding sildenafil to bosentan therapy does not result in any beneficial effect on exercise capacity.
• Tracleer
  • For the treatment of pulmonary arterial hypertension (PAH) (WHO Group 1) to improve exercise ability and to decrease clinical worsening:
    • in adults to improve exercise ability and to decrease clinical worsening. Studies establishing effectiveness included predominantly patients with WHO Functional Class II-IV symptoms and etiologies of idiopathic or heritable PAH (60%), PAH associated with connective tissue diseases (21%), and PAH associated with congenital heart disease with left-to-right shunts (18%).
    • in pediatric patients aged 3 years and older with idiopathic or congenital PAH to improve pulmonary vascular resistance (PVR), which is expected to result in an improvement in exercise ability.
• Uptravi
  • For the treatment of pulmonary arterial hypertension (PAH, WHO Group I) to delay disease progression and reduce the risk of hospitalization for PAH.

Rationale:

Oral PAH medications have been used in attempts to treat conditions that have not been validated by the FDA or improperly diagnosed. This program ensures that members are receiving this medication for conditions that have the appropriate evidence to support its use.

Criteria Summary:

FDA approved use/Medical necessity

Criteria for Approval of Adcirca, Letairis, Opsumit, Orenitram, Revatio, Tracleer, and Uptravi:

1. The requested medication is being used for treatment of pulmonary arterial hypertension (PAH/WHO Group 1) ; AND
2. The patient’s symptoms are Functional Class 2 through 4; AND
3. For formularies that exclude (non-formulary) the requested medication, Non-formulary Exception Criteria applies (outlined below)*

Criteria for Approval of Adempas:

1. The requested medication is being used for treatment of pulmonary arterial hypertension (PAH/WHO Group 1); OR
2. The requested medication is being used for treatment of Chronic Thromboembolic Pulmonary Hypertension (CTEPH/WHO Group 4); AND
3. The patient’s symptoms are Functional Class 2 through 4; AND
4. For formularies that exclude (non-formulary) the requested medication, Non-formulary Exception Criteria applies (outlined below)*

Duration of Approval: 1095 days (3 years)

*Non-formulary Exception Criteria

Non-Formulary Exception criteria applies on formularies which exclude requested product(s). Satisfactory completion of criteria points (above) may satisfy some, or all, portions of the Non-Formulary Exception Criteria. This criteria is summarized as:

1. Request must be for an FDA approved indication; AND
2. Patient must have a trial and failure of up to TWO formulary medications or a clinical contraindication/intolerance to those medications not tried.

References:

All information referenced is from FDA package insert unless otherwise noted below.

1. Taichman DB, Ornelas J, Chung L, Klinger JR, Lewis S. Pharmacologic Therapy for Pulmonary Arterial Hypertension in Adults;CHEST Guideline and Expert Panel Report. Chest. 2014;146(2): 449-475. doi:10.1378/chest. 14-0793
   • WHO Groups
     1. Group 1- Pulmonary arterial hypertension (PAH)
        1. Idiopathic (IPAH)
        2. Heritable (HPAH)
           1. Bone morphogenetic protein receptor type 2 (BMPR2)
           2. Activin receptor-like kinase 1 gene (ALK1), endoglin (with or without haemorrhagic telangiectasia)
           3. Unknown
        3. Drug- and toxin-induced
        4. Associated with (APAH):
           1. Connective tissue diseases
           2. Human immunodeficiency virus (HIV) infection
           3. Portal hypertension
           4. Congenital heart disease (CHD)
           5. Schistosomiasis
           6. Chronic hemolytic anemia
        5. Persistent pulmonary hypertension of the newborn (PPHN)
     2. Group 1'- Pulmonary veno-occlusive disease (PVOD) and/or pulmonary capillary haemangiomatosis (PCH)
     3. Group 2- Pulmonary hypertension due to left heart diseases
        1. Systolic dysfunction
        2. Diastolic dysfunction
        3. Valvular disease
     4. Group 3- Pulmonary hypertension due to lung diseases and/or hypoxemia
        1. Chronic obstructive pulmonary disease (COPD)
        2. Interstitial lung disease (ILD)
        3. Other pulmonary diseases with mixed restrictive and obstructive pattern
        4. Sleep-disordered breathing
        5. Alveolar hypoventilation disorders
        6. Chronic exposure to high altitude
        7. Developmental abnormalities
     5. Group 4- Chronic thromboembolic pulmonary hypertension (CTEPH)
     6. Group 5- PH with unclear multifactorial mechanisms
        1. Haematological disorders: myeloproliferative disorders, splenectomy
        2. Systemic disorders: sarcoidosis, pulmonary Langerhans cell histiocytosis, lymphangioleiomyomatosis, neurofibromatosis, vasculitis
        3. Metabolic disorders: glycogen storage disease, Gaucher disease, thyroid disorders
        4. Others: tumoral obstruction, fibrosing mediastinitis, chronic renal failure on dialysis
   • WHO Functional Class -The World Health Organization (WHO) has developed a system to help doctors determine how limited a patient is in their ability to do the activities of daily living. In general, patients with more severe PH tend to have a higher functional class.
     1. Class I: Patients with pulmonary hypertension but without resulting limitation of physical activity. Ordinary physical activity does not cause undue dyspnea or fatigue, chest pain, or near syncope
     2. Class II: Patients with pulmonary hypertension resulting in slight limitation of physical activity. They are comfortable at rest. Ordinary physical activity causes undue dyspnea or fatigue, chest pain, or near syncope.
     3. Class III: Patients with pulmonary hypertension resulting in marked limitation of physical activity. They are comfortable at rest. Less than ordinary activity causes undue dyspnea or fatigue, chest pain, or near syncope.
     4. Class IV: Patients with pulmonary hypertension with inability to carry out any physical activity without symptoms. These patients manifest signs of right heart failure. Dyspnea and/or fatigue may even be present at rest. Discomfort is increased by any physical activity.

Policy Implementation/Update Information:

Originated: January 2011; last updated: July 2019

July 2019: Criteria update: Added “brand and generic formulations” to restricted section

May 2019: Criteria update: Changed duration of approval to 1095 days (3 years)

Oct 2018: Annual review; No change

Oct 2017: Annual review; No change

Sep 2017: Update on indication to include pediatric population on Tracleer; no change to criteria.

June 2017: Reformatted criteria; clarified Adempas coverage to those with WHO group 4 w/ functional class 2-4.

January 2017: Adjusted criteria to reflect continuation of therapy present in system coding; Reviewed for Net Results formulary; added Non-

Formulary verbiage

August 2016: Updated policy based on clinical guidelines; addition of functional class as a limitation of coverage; addition of vasoreactivity testing and CCB therapy as a limitation of coverage; addition of PDE5-I and ERA therapy prior to the use of Orenitram or Uptravi as a limitation of coverage

December 2015: Policy revised to add new to market drug Uptravi.

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