National CooperativeRx constantly monitors the pharmaceutical pipeline. As treatment options change, it’s important to know how those changes could impact your plan and which drugs bring the highest value. Our quarterly NCRx Pipeline Reports highlight some of the newest therapies coming to market and are not intended to imply formulary placement or coverage by CVS Caremark.
Orladeyo® (berotralstat): Approved by the U.S. Food and Drug Administration (FDA) on December 3, 2020, this is the first oral medication to prevent hereditary angioedema (HAE) attacks. HAE is a rare condition which causes episodes of skin and mucous membrane swelling in various locations in the body. Attacks occurring in the airways are the most serious and can be fatal. There are currently four drugs available to prevent these episodes. Takhzyro® (lanadelumab) is a subcutaneous product with the same molecular target as Orladeyo® and is currently the market leader in this category. It’s expected that Orladeyo® will slowly gain favor, with a projection of 30% market share by 2023. Initial clinical trial data suggests that Orladeyo® may be less effective than its competitors. A six-month placebo-controlled trial showed a 44% reduction in attacks for Orladeyo,® compared to reductions of 87% and 84% for Takhzyro® and Haegarda,® respectively, in separate placebo-controlled trials.1,2,3 However, a more complete data set became available in June 2020, showing that efficacy of Orladeyo® improved to 66% when remeasured after one year of therapy.4 Orladeyo® seems to have been priced in consideration of its efficacy compared to other drugs in this category at $485,000 per year, versus $591,000 for Takhzyro® and $503,000* for Haegarda.® All things considered, being an oral option in this class at the lowest price gives Orladeyo® the potential to establish itself as a first-line therapy.
*based on a patient weight of 80kg
Anticipated Launch: Late December 2020.
Impact: Low. HAE affects one out of 50,000 people. Orladeyo® will represent replacement spend in most cases, since patients are likely already using one of the other three available medications in the class.
Price: $486,000 annually per patient.
Imcivree® (setmelanotide): After being granted orphan drug status by the FDA, Imcivree® was approved on November 27, 2020 for the treatment of obesity caused by three rare genetic conditions: pro-opiomelanocortin (POMC) deficiency, proprotein subtilisin/kexin type 1 (PCSK1) deficiency, and leptin receptor (LEPR) deficiency. There are only about 150 cases reported in the medical literature for all three conditions combined. The drug is not intended for treatment of obesity in patients with benign genetic mutations in these genes or in other types of obesity. People with obesity due to POMC, PCSK1 or LEPR deficiency have increased hunger, and decreased metabolism and feelings of fullness. Imcivree® works by inducing weight loss; it does not treat the genetic mutation. Approval of the drug was based mainly on two small trials. 80% of participants in one trial and 45% of participants in the second trial achieved at least 10% weight loss at one year.5,6 The most common adverse events were injection site reaction, dark spots on the skin, nausea, and vomiting. No serious treatment-related adverse events occurred in either trial.
Anticipated Launch: Quarter one of 2021.
Impact: Extremely low. There are only about 150 cases reported in the medical literature for all three conditions combined. However, the manufacturer estimates there may be a significant number of undiagnosed cases: around 600-2,500 cases in the U.S. Furthermore, clinical trials are being conducted for several additional indications.
Price: Currently unknown, but some are predicting a price greater than $300,000 per year for an adult.
Xofluza® (baloxivir): Xofluza® is an antiviral medication approved in 2018 for treatment of influenza. While there are several other drugs available for this indication, oseltamivir (Tamiflu®) is the most widely used and is also approved for prevention of influenza. On November 23, 2020, the FDA approved Xofluza® to prevent influenza in a patient exposed to the illness. In a study comparing Xofluza® and oseltamivir for prevention of influenza in patients exposed to a household member with influenza, 9% of patients in the Xofluza® group and 13% of patients in the oseltamivir group became infected with influenza.7 It’s important to note, however, there were 49 patients in the Xofluza® group and 120 patients in the oseltamivir group, weakening the conclusion drawn from the Xofluza® data. In a separate placebo-controlled trial, oseltamivir reduced the incidence of symptomatic influenza by 89%.8 While the two drugs have similar efficacy, Xofluza® is priced significantly higher at around $150 for its one-dose post-exposure preventative regimen* and oseltamivir can be obtained for less than $30.** CVS’ Advanced Control Formulary includes oseltamivir as a preferred generic. Xofluza® is not covered and would require a medical necessity prior authorization for coverage.
*for an 80kg adult
**for a high-risk adult
Anticipated Launch: Currently available.
Impact: Low to moderate. The influenza season is expected to be mild this year, based on the experience of countries in other parts of the world who have their flu season earlier in the year. However, media reports of a possible “twindemic” of influenza and COVID-19 may contribute to additional fear and requests for these treatments.
Price: Around $150 for a one-dose post-exposure preventative regimen.
Kesimpta®: Approved on August 20, 2020, Novartis’ Kesimpta® became the first self-administered B-cell therapy for relapsing forms of multiple sclerosis (MS). Ocrevus® is also a B-cell therapy but is administered intravenously (IV) every six months, whereas Kesimpta® will be dosed subcutaneously once monthly. Ocrevus® has gained favor with neurologists in recent years, owing to its robust ability to prevent relapse compared to other agents. In clinical trials, Ocrevus had an annualized relapse rate (ARR) of 0.16,9 which essentially equates to one MS relapse every six years on average. In separate clinical trials, Kesimpta® produced ARRs of 0.1 and 0.11.10 Older, existing MS therapies were comparator products in these trials and had ARRs of 0.22-0.29,9,10 so the reduction in ARR with Ocrevus® and Kesimpta® was quite dramatic. The safety profile of these B-cell therapies appears to be like older MS drugs, with the exception of more injection-related reactions. Kesimpta® and Ocrevus® are preferred products on CVS’ Advanced Control Specialty Formulary.
Anticipated Launch: Launches began in September 2020 in some states but were delayed in others due to the COVID-19 pandemic.
Impact: Moderate. It’s most likely to take market share from other MS drugs in newly diagnosed patients. There are approximately 1 million people with MS in the U.S.
Price: $83,000 per year. Ocrevus® is priced at $65,000 per year, but additional costs are incurred for IV administration, which may make Kesimpta® the lowest total cost option.
Eysuvis® (loteprednol etabonate): Eysuvis® is a steroid eye drop solution for the short-term treatment of dry eye symptoms, like redness and discomfort. It can be used to treat dry eye symptom flares, or for short-term relief when starting a maintenance therapy which can take several weeks to work. Generally, steroids are used for dry eye symptoms after first-line treatments, such as warm compresses and eye lubricants, have failed. Eysuivs® demonstrated a significant reduction in conjunctival hyperemia (appearance of tiny red vessels in the white part of the eye) in three clinical trials, and a reduction in eye discomfort in two of three trials.11 As with any steroid eye drop, Eysuvis® shouldn’t be used if there is any type of infection in the eye or history of cataracts or glaucoma. While Eysuvis® is the first steroid eye drop to gain FDA approval for use in dry eye disease, there are several generic products in this category that have been used for many years via off-label prescribing. Eysuvis® is not covered on CVS’ Advanced Control Formulary and would require a medical necessity prior authorization for coverage.
Anticipated Launch: Currently available.
Impact: Low to moderate. There are 16 million people in the U.S. with dry eye disease.
Price: $465 for an 8.3mL bottle. A bottle of fluorometholone, an alternative steroid eye drop, costs $67.
Prices for brand-name products are expressed using Wholesale Acquisition Cost (WAC) and prices for generics use National Average Drug Acquisition Cost (NADAC).
- Zuraw B, Lumry W, Johnston D, et al. Oral once-daily berotralstat for the prevention of hereditary angioedema attacks: A randomized, double-blind, placebo-controlled phase three trial. J Allergy Clin Immunol
- Longhurst H, Cicardi M, Craig T et al. Prevention of hereditary angioedema attacks with a subcutaneous C1 inhibitor. N Engl J Med 2017; 376:1131-1140.
- Banerji A , Riedl MA, Bernstein JA et al. Effect of Lanadelumab Compared With Placebo on Prevention of Hereditary Angioedema Attacks: A Randomized Clinical Trial. JAMA 2018 Nov; 320(20):2108-2121.
- Long-term (48-week) Data Show Treatment with Berotralstat Provides Robust and Durable Reductions in HAE Attacks and Improvements in Quality of Life Scores. June 2020. Accessed at: https://ir.biocryst.com/node/21411/pdf
- Setmelanotide for the Treatment of Early-Onset POMC Deficiency Obesity. gov identifier: NCT02896192. https://clinicaltrials.gov/ct2/show/NCT02896192. Accessed December 10, 2020.
- Setmelanotide for the Treatment of LEPR Deficiency Obesity. gov identifier: NCT03287960. https://clinicaltrials.gov/ct2/show/NCT03287960. Accessed December 10, 2020.
- Umemura T, Mutoh Y, Kawamura T, et al. Efficacy of baloxavir marboxil on household transmission of influenza infection. J Pharm Health Care Sci 2020 Oct; 6:21
- Welliver R, Monto AS, Carewicz O, et al. Effectiveness of Oseltamivir in Preventing Influenza in Household Contacts: A Randomized Controlled Trial. JAMA 2001;285(6):748-754.
- Package insert. Genentech, Inc. Revised 2017. Accessed December 15, 2020.
- Hauser SL, Bar-Or A, Cohen JA, et al. Ofatumumab versus Teriflunomide in Multiple Sclerosis. N Engl J Med 2020; 383:546-557.
- Package insert. Kala Pharmaceuticals. Revised 2020. Accessed December 15, 2020.
