Coverage of Cinryze

[chantell.reagan]

Cinryze, the first IV C1-esterase inhibitor, was approved by the FDA in October 2008 for the prevention of hereditary angioedema (HAE). HAE is a rare, genetic disorder, caused by a deficiency of the plasma protein, C1 esterase inhibitor (C1-INH), a naturally occurring molecule that inhibits plasma kallikrein, a key mediator of inflammation, and other serine proteases in the blood. HAE is characterized by recurrent episodes of swelling in extremities, face, trunk, abdominal viscera, and upper airway. There are 2 main types of HAE: Type I, the most common form affecting 85% of patients, is characterized by low C1-inhibitor levels. Type II HAE (accounting for the other 15%), where antigenic C1-inhibitor levels are normal but functional C1-inhibitor levels are low. HAE occurs in about 10,000-50,000 people in the US. Severity may vary, with frequency of attacks ranging from less than once a year to every 3 days (average frequency is approximately every 7 to 14 days). There are four additional drugs in the late-stage pipeline for HAE; two are scheduled to be reviewed by FDA this year, one of them will be SC (see more details in the HAE pipeline outlook). As plans prepare to review Cinryze and other HAE agents this year, there are several points to consider:

•What is the percentage of my population that might be affected by HAE? HAE is a rare genetic disorder; it’s estimated that approximately 1 in 50,000 people might be affected. However, severity may vary and the percentage of the HAE population that requires long-term prophylaxis has not been officially estimated.
•What are key diagnostic considerations/restrictions? It is reported that most patients with HAE have a persistently low C4 level and low antigenic or functional C1-inhibitor levels. Unlike those with idiopathic or allergic angioedema, patients with HAE do not respond to antihistamines, corticosteroids, or epinephrine for acute attacks.
•What is the place in therapy for Cinryze? Cinryze has been approved for routine prophylaxis; this is the first therapy specifically approved for HAE. However, C1-inhibitor replacement therapy has been available in Europe for more than 20 years. According to the consensus statement published by the British Society of Immunology in 2005, long-term C1-inhibitor prophylaxis may be needed for patients who have not responded to preventative therapy with anabolic androgens such as danazol, oxandrolone or antifibrinolytic agents such as aminocarproic acid (or in cases of intolerance/contraindication). In some patients, short-term prophylaxis with C1-inhibitor therapy might be required before exposure to a known trigger (eg, dental or surgical procedures). It should also be noted that C1-inhibitor therapy is also considered the standard of care for acute attacks, especially for severe episodes. Although, Cinryze is not indicated for acute treatment at this time, the manufacturer expects an expanded indication in June 2009.
•Should any provider, age restrictions or quantity limits be considered? Patients experiencing HAE are likely be seen by an allergist, dermatologist, hematologist, or immunologist. Although Cinryze is indicated only for adults and adolescents, there is a small percentage of children that might be affected by severe HAE. Lastly, the recommended dosing for Cinryze, according to the PI, is 1000u given IV every 3 or 4 days for routine prophylaxis (the product is packaged as 500u/8ml vials). Frequent infusions may require additional ancillary services such as home infusion.
•How could this therapy affect my budget? The AWP for Cinryze is $2,437.50 per vial; at this benchmark monthly cost of therapy would range between $36,562 to $48,750 per patient.

Sources:
• Cinryze prescribing information

• Zuraw BL. Clinical practice. Hereditary angioedema. N Engl J Med. 2008 Sep 4;359(10):1027-36 (reference only; full-text not available)

• C1 inhibitor deficiency: consensus document – British Society of Immunology/2005

•United States Hereditary Angioedema Association - A resource for physicians and patients

• National Organization for Rare Disorders: Hereditary Angioedema

• Caremark: Specialty Pharmacy Pipeline Drugs To Watch 1-2Q09

[chantell.reagan]

It has been approximately 8 months since the FDA approval of the first C-1 esterase inhibitor (Cinryze) for use in hereditary angiodema (HAE) prophylaxis in adults and adolescents. We analyzed 6 local and national plans for their Cinryze coverage criteria and the following are our key findings:

o 3/6 plans set certain laboratory requirements for confirming HAE diagnosis; however, specific thresholds tended to vary
o 5/6 plans required specific frequency or severity/location of symptomatic HAE attacks
o 5/6 plans required failure of traditional HAE therapies, such as attenuated androgens (danazol or stanozolol) but only 3 of them recognized failure of anti-fibrinolytic agents (epsilon aminocaproic acid [EACA] or tranexamic acid).
o None of the plans currently provide coverage for acute attacks. Note that the manufacturer did submit an sBLA for this indication, but according to the FDA an additional study is warranted before approval can be considered. In addition, there are 4 products in the late-stage pipeline that are being studied for acute attacks only – see our related discussion on pipeline outlook in HAE

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Sources:

Cinryze prescribing information

News article 6/09

DrugPipelineForecast

BlueCross BlueShield of Alabama. Cinryze policy (link provided in the attachment)

BlueCare Network of Michigan/BCN Advantage: BCN Step Therapy and Prior Authorization requirements (link provided in the attachment)

HealthPartners: Cinryze (link provided in the attachment)

The Regence Group. Cinryze policy (link provided in the attachment)

Wellmark: Cinryze medical policy (link provided in the attachment)

Aetna. Clinical Policy Bulletin: Cinryze (link provided in the attachment)

[diana.papshev]

Anonymous response:

"We have no medical policy covering this drug, which means it is available to our members, subject to whatever contractual coverage limits, deductibles, etc. they may have."