Effective Date

Date of Origin 

01-01-2025            

10-01-2024

Voydeya™

(danicopan)

Tablet

Add-on therapy to ravulizumab or eculizumab for the treatment of extravascular hemolysis (EVH) in adults with paroxysmal nocturnal hemoglobinuria (PNH)

Limitations of Use:

• Voydeya has not been shown to be effective as monotherapy and should only be prescribed as an add-on to ravulizumab or eculizumab.

1

Paroxysmal Nocturnal Hemoglobinuria

Paroxysmal nocturnal hemoglobinuria (PNH) is a chronic, progressive, life-threatening, rare, multi-systemic disease developing as a result of a somatic mutation of hematopoietic stem cells, and characterized by clonal, complement-mediated intravascular hemolysis. PNH is mainly a disease of adults with a median age of onset in the thirties. High precision flow cytometry is the most useful and accepted diagnostic test to confirm the diagnosis of PNH. Flow cytometry is performed by incubating the patient’s peripheral blood cells with fluorescently-labeled monoclonal antibodies that bind to glycosylphosphatidylinositol (GPI) anchored proteins, which are reduced or absent on blood cells in PNH. Since different blood cell lineages display different combinations of GPI-linked proteins, and some proteins bind to cell surfaces via both GPI-linked and GPI-independent mechanisms, it is recommended that at least two independent flow cytometry reagents be used on at least two cell lineages (e.g., red blood cells [RBCs] and white blood cells [WBCs]) to establish a diagnosis of PNH.(2)

The lack of the complement inhibitor CD59 on RBCs surface is mostly responsible for the clinical manifestations in PNH. These patients manifest with chronic intravascular hemolysis, paroxysmal flares of hemolysis and a propensity for thrombosis. Intravascular hemolysis leads to release of free hemoglobin (Hb) into the blood. Free Hb, in turn, can cause various toxic effects, including hypercoagulability, changes in vascular tone from reduction of circulating nitric oxide and renal damage.(3)

Extravascular hemolysis also occurs in patients with PNH because C3 fragments that are not destroyed by the membrane attack complex (MAC) intravascularly can accumulate on the GPI-negative RBCs (lacking CD55) surface and these fragments opsonize the RBCs, causing reticuloendothelial destruction in the liver and spleen.(3)

The main clinical situations or diseases that should be considered in the differential diagnosis of PNH are:(3)

• Coombs-negative hemolytic anemia (e.g., hemoglobinopathies, hereditary spherocytosis), microangiopathic hemolytic anemias, drug- or toxin-induced hemolysis/anemias, disseminated intravascular coagulation, and autoimmune hemolysis
• Venous thrombosis in atypical sites, including myeloproliferative disorders; solid tumors associated with hypercoagulability; extrinsic compression of vessels, and; inherited/acquired thrombophilias
• Anemia and/or other cytopenias related to bone marrow failure syndrome (e.g., aplastic anemia, myelodysplastic syndrome [MDS])

PNH is classified into three different categories:(3)

• Classic PNH (PNH with clinical and laboratory findings of intravascular hemolysis without any evidence of bone marrow deficiency)
• PNH in the setting of another specified bone marrow disorder (evidence of hemolysis, as well as another specified bone marrow disorder [e.g., aplastic anemia, MDS])
• Subclinical PNH (patients with a small population of PNH cells and no clinical or laboratory evidence of hemolysis or thrombosis)

Historically, patients with PNH had a median survival of ten years after diagnosis however, since the development of complement inhibitors survival rates have improved to approximately 75%.(4) The approach to therapy depends on the severity of symptoms and the degree of hemolysis. The treatment options for PNH are supportive care, allogenic hematopoietic stem cell transplantation (HSCT) and a complement blockade.(2,3)

Efficacy

Danicopan is a first-in-class oral inhibitor of complement factor D (FD; a component of the alternative complement pathway) that can control signs and symptoms of extravascular hemolysis as an add-on treatment in patients receiving a C5 complement inhibitor (C5i; eculizumab, ravulizumab).(1)

The efficacy of Voydeya in adults with PNH and clinically significant extravascular hemolysis (EVH) was assessed in a multiple-region, randomized, double-blind, placebo-controlled study (NCT04469465). Clinically significant EVH was defined by anemia (Hb less than or equal to 9.5 g/dL) with absolute reticulocyte count greater than or equal to 120 × 10^9/L with or without transfusion support. The study enrolled patients with PNH who had been treated with a stable dose of ravulizumab or eculizumab for at least the previous 6 months.(1)

Preliminary results of a phase 3 trial indicate that, for patients with clinically significant extravascular hemolysis while receiving ravulizumab or eculizumab, addition of danicopan was superior to addition of placebo for reducing transfusions and elevating Hb, with little toxicity and continued control of intravascular hemolysis.(1)

Safety

Voydeya contains the following boxed warnings:(1)

Voydeya increases the risk of serious infections, especially those caused by encapsulated bacteria, such as Neisseria meningitidis, Streptococcus pneumoniae, and Haemophilus influenzae type B. Life-threatening and fatal infections have occurred and these infections may become rapidly life-threatening or fatal if not recognized and treated early.

• Complete or update vaccination for encapsulated bacteria at least 2 weeks prior to the first dose of Voydeya, unless the risks of delaying Voydeya therapy outweigh the risk of developing a serious infection. Comply with the most current Advisory Committee on Immunization Practices (ACIP) recommendations for vaccinations against encapsulated bacteria.
• Patients receiving Voydeya are at increased risk for invasive disease caused by encapsulated bacteria, even if they develop antibodies following vaccination. Monitor patients for early signs and symptoms of serious infections and evaluate immediately if infection is suspected.

Voydeya is contraindicated in the following:(1)

• Initiation in patients with unresolved serious infection caused by encapsulated bacteria, including Neisseria meningitidis, Streptococcus pneumoniae, or Haemophilus influenzae type B

Voydeya is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called VOYDEYA REMS.(1)

1

Voydeya prescribing information. Alexion Pharmaceuticals, Inc. March 2024.

2

Sahin Fahri, MeltemF, Akay OOM, Ayer M, et al. Pesg PNH diagnosis, follow-up and treatment guidelines. Am J Blood Res.PubMed Central (PMC). Published 2016;6(2):19-27.. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4981648/

3

Rodolfo D. Cançado, Aderson da Silva Araújo, Alex Freire Sandes, Celso Arrais, Clarisse Lopes de Castro Lobo, Maria Stella Figueiredo, Sandra Fátima Menosi Gualandro, Sara Teresinha Olalla Saad, Fernando Ferreira Costa.Cançado RD, Da Silva Araújo A, Sandes AF, et al. Consensus statement for diagnosis and treatment of paroxysmal nocturnal haemoglobinuria. Hematology, Transfusion and Cell Therap. 2020.Therapy. 2021;43(3):341-348. doi:10.1016/j.htct.2020.06.006

4

Shah N, Bhatt H. Paroxysmal nocturnal hemoglobinuria. StatPearls - NCBI Bookshelf. Published July 31, 2023. https://www.ncbi.nlm.nih.gov/books/NBK562292/

Voydeya

danicopan tab  ; danicopan tab therapy pack

100 MG ; 50 & 100 MG

M ; N ; O ; Y

N

Voydeya

danicopan tab

100 MG

180

Tablets

30

DAYS

Voydeya

danicopan tab therapy pack

50 & 100 MG

1

Box

30

DAYS

Voydeya

danicopan tab  ; danicopan tab therapy pack

100 MG ; 50 & 100 MG

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

Voydeya

danicopan tab

100 MG

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

Voydeya

danicopan tab therapy pack

50 & 100 MG

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

Initial Evaluation

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

1. ONE of the following:
   1. The patient has a diagnosis of paroxysmal nocturnal hemoglobinuria (PNH) AND ALL of the following: 
      1. The diagnosis was confirmed by flow cytometry with at least 2 independent flow cytometry reagents on at least 2 cell lineages (e.g., RBCs and WBCs) demonstrating that the patient’s peripheral blood cells are deficient in glycosylphosphatidylinositol (GPI) – linked proteins (lab tests required) AND
      2. The patient has clinically significant extravascular hemolysis (EVH) as indicated by BOTH of the following:
         1. Hemoglobin less than or equal to 9.5 g/dL (lab tests required) AND
         2. Absolute reticulocyte count greater than or equal to 120 x 10^9/L with or without transfusion support (lab tests required) AND
      3. BOTH of the following:
         1. The patient has been treated on a stable dose of Soliris (eculizumab) or Ultomiris (ravulizumab-cwvz) for at least the previous 6 months AND
         2. The patient will be using the requested agent as add-on therapy to Soliris (eculizumab) or Ultomiris (ravulizumab-cwvz) OR
   2. The patient has another FDA labeled indication for the requested agent and route of administration AND
2. 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
3. The prescriber is a specialist in the area of the patient’s diagnosis (e.g., hematologist) or the prescriber has consulted with a specialist in the area of the patient’s diagnosis AND
4. The patient will NOT be using the requested agent in combination with Empaveli (pegcetacoplan), Fabhalta (iptacopan), or Piasky (crovalimab-akkz) for the requested indication AND
5. The patient does NOT have any FDA labeled contraindications to the requested agent 

Length of Approval: 3 months

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

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 clinical benefit with the requested agent AND
3. The prescriber is a specialist in the area of the patient’s diagnosis (e.g., hematologist) or the prescriber has consulted with a specialist in the area of the patient’s diagnosis AND
4. The patient will be using the requested agent as add-on therapy to Soliris (eculizumab) or Ultomiris (ravulizumab-cwvz) AND
5. The patient will NOT be using the requested agent in combination with Empaveli (pegcetacoplan), Fabhalta (iptacopan), or Piasky (crovalimab-akkz) 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

Universal QL

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. The requested quantity (dose) exceeds the program quantity limit AND ONE of the following:
   1. BOTH of the following:
      1. The requested agent does NOT have a maximum FDA labeled dose for the requested indication AND
      2. There is support for therapy with a higher dose for the requested indication OR
   2. BOTH of the following:
      1. The requested quantity (dose) does NOT exceed the maximum FDA labeled dose for the requested indication AND
      2. There is support for why 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. BOTH of the following:
      1. ​​​​The requested quantity (dose) exceeds the maximum FDA labeled dose for the requested indication AND
      2. There is support for therapy with a higher dose for the requested indication 

Length of Approval:  up to 12 months