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Manage High-Cost Therapies for Rare Disease
Specialty Pharmacy Pipeline | Drugs to Watch
Anticipated Launches | Q3 – Q4 2020
For the past dozen years, patients with hereditary angioedema (HAE) have witnessed the expansion of treatment options. Since 2008, when Cinryze was approved, HAE treatments have grown to seven injectable therapies available for either prevention or treatment of acute attacks. The first preventive oral agent is expected in the fourth quarter of 2020.
What is HAE?
HAE is a debilitating rare genetic disease that causes swelling affecting different parts of the body but is not treatable using antihistamines, epinephrine, or corticosteroids.
It is believed that one in 10,000 to one in 50,000 people have HAE and it affects males and females equally, with symptoms starting in early childhood.
While the HAE population is relatively small, treatments are expensive and, without a cure, patients are required to continue medication for the rest of their lives. This makes it important to help ensure member access but also careful management to ensure appropriate utilization.
HAE treatments fall into two categories - some work to prevent attacks from occurring (preventive), while others are used when attacks happen (acute). Some of the therapies help to restore the balance of a blood protein, C1 esterase inhibitor (C1-INH). The C1-INH imbalance causes swelling. Of the three types of HAE, 85 percent of all patients are diagnosed with type I (low C1-INH) and 15 percent with type II (poorly functioning C1-INH). Few patients are diagnosed with HAE with normally functioning C1-INH (formerly known as type III), which was identified in 2000.
|Name||Drug Class||Route of Administration||Patient Age|
|Cinryze (C1 esterase inhibitor [human])||C1-esterase inhibitor protein||IV||Children 6 years and over, adolescents, and adults|
|Haegarda (C1 esterase inhibitor [human])||C1-esterase inhibitor protein||SC||Adolescents 12 years and over and adults|
|Takhzyro (lanadelumab-flyo [recombinant])||Kallikrein inhibitor||SC||Adolescents 12 years and over and adults|
|Annual preventive treatments cost more than $500,000 on average.|
Cinryze, from Takeda, was the first preventive treatment approved by the U.S. Food and Drug Administration (FDA) and is available for patients six years and older. It is administered through an intravenous (IV) infusion every three to four days.
Nearly 10 years after Cinryze came to market, CSL Behring launched Haegarda as the first subcutaneous (SC) C1-INH preventive treatment. Similar to many of the earlier treatments, Haegarda works to replace the missing or dysfunctional C1-INH protein. Its subcutaneous delivery allows for a more gradual diffusion of the medication, as well as being generally preferred by patients compared with IV use, because they can learn to self-administer it.
Two years ago, Takeda’s Takhzyro came to market after a priority review by the FDA, with both an Orphan drug and Breakthrough Therapy designation. Clinical trials demonstrated that this kallikrein inhibitor resulted in a significant reduction in average HAE attack frequency compared to placebo over a 26-week treatment period.
|Name||Drug Class||Route of Administration||Patient Age|
|Berinert (C1 inhibitor [human])||C1-esterase inhibitor protein||IV||Children 6 years and over, adolescents, and adults|
|Firazyr (icatibant acetate)||Selective B2 bradykinin receptor antagonist||SC||Adults, 18 years and older|
|Kalbitor (ecallantide)||Kallikrein inhibitor||SC||Adolescents 12 years and over and adults|
|Ruconest (C1 esterase inhibitor [recombinant])||C1-esterase inhibitor protein||IV||Adolescents 13 years and over and adults|
|Approximate treatment cost for each acute HAE attack can exceed $11,000.|
Similar to Cinryze, Berinert, CSL Behring’s HAE medication approved in 2009, is also a human plasma-derived C1-esterase inhibitor treatment administered by IV. However, Berinert is not a preventive treatment. It is approved to treat acute abdominal, laryngeal, or facial attacks in adults and children, and can be self-administered.
The FDA approved Kalbitor, the first subcutaneous treatment for acute HAE attacks, for patients 12 years and older.
Another of the Takeda HAE treatments, Firazyr received FDA approval in 2011. As a selective B2 bradykinin receptor antagonist, Firazyr targets the bradykinin protein that can lead to attacks. Approved for those 18 years and older, the subcutaneous therapy is also portable and can be self-administered, which allows patients to receive treatment at home or at the office of a health care professional.
Ruconest, a manmade therapy from Pharming, received FDA approval in 2014. As the first recombinant IV-administered C1-esterase inhibitor, it can be manufactured without the need to rely on the availability (or safety) of human plasma. Patients aged 13 and older can learn how to self-administer Ruconest, which is sold as a powder to create a solution.
In the Pipeline
In December 2019, the FDA accepted a new drug application for berotralstat from BioCryst.
|In the past 12 years, treatments have increased options for and started shifting standard of care for HAE patients.|
Although there remains no cure for HAE, developments in the drug pipeline offer many patients hope while potentially altering client spend.
Trend and Pipeline Management
Overall spend on HAE treatments are likely to rise because of increased diagnosis, more treatments coming to market, and growth in the use of preventive treatments.
|Medical director review is required for all new and renewal requests for HAE medications prior to approval or denial.|
|Advanced Utilization Oversight, a retrospective clinician review conducted for high cost claims, ensures HAE criteria are appropriately applied and include a comprehensive review of members’ overall therapy.|
|We leverage competition within the class to help lower costs. For instance, we exclude certain products from our standard template formulary, while Takhzyro, Firazyr and Ruconest are preferred.|
|Our SGM criteria is developed from clinical literature, nationally accepted practice guidelines and consensus statements. It is evaluated by the Clinical Program Oversight (CPO) Review Process, which includes criteria review by CVS Caremark Medical Directors and appropriate external clinical experts.|
HAE is also part of the AccordantCare Rare nurse care management program. Specialized AccordantCare teams — comprised of registered nurses, social workers, and a medical director, all backed by a medical advisory board — offer whole-person support for plan members with rare conditions through targeted interventions designed to meet each person’s unique needs. This helps members better manage their condition, as well as comorbidities and side effects, for improved outcomes.
*Frequency and severity of attacks vary.
This document contains references to brand-name prescription drugs that are trademarks or registered trademarks of pharmaceutical manufacturers not affiliated with CVS Health.
Image source: Licensed from Getty Images, 2020.