NCRx Pipeline Report 4.1.21

Erica Guetzlaff  •   April 1, 2021

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.

Varenicline (Chantix®): A popular oral tobacco cessation drug, Chantix® has been on the market since 2006 and is finally expected to see generic competition in the first half of 2021. The drug works to reduce cravings and nicotine withdrawal symptoms and is taken twice daily for at least three months and up to one year. It tends to be more effective than its major competitor, bupropion (Zyban®), early on in treatment1, but its superiority is lost at the one-year mark when both therapies demonstrate a success rate of about 20%.2 In general, tobacco cessation drug products have still proven to be better than placebo, and there are some defining properties of each of them. Varenicline and bupropion are oral treatments which reduce cravings and withdrawal symptoms and allow for a flexible quit date but must be used with caution in patients with history of certain psychiatric disorders, seizures, and heart disease. Nicotine-replacement products help with withdrawal symptoms, and some of them provide options for flexible or “hands-on” dosing; these are helpful features for people who may require booster doses throughout the day or having a device in hand to replace a cigarette. Many times, varenicline or bupropion is combined with nicotine replacement products for greater efficacy. Of all the tobacco cessation drug options, Chantix® has been the most expensive to date at $456* per month, so a generic will be a welcome addition to the class. We expect CVS to include varenicline on its Affordable Care Act drug list in the Tobacco Cessation category.

*Wholesale acquisition cost

Anticipated Launch: Second Quarter 2021.

Impact: High. Chantix® is one of the most popular tobacco cessation products on the market, so a decrease in cost will be impactful for spend in this category.

Price: With four potential generic entrants to the marketplace, we may see cost savings sooner than later. Savings of 80% versus brand cost are not unusual in this instance.

Tanezumab: A first-in-class medication, tanezumab is a monoclonal antibody which inhibits nerve growth factor for moderate to severe osteoarthritis that is resistant to other medications. Tanezumab works differently than non-steroidal anti-inflammatory drugs (NSAIDs) and opioids in that it stops the pain signal from reaching the brain. In a clinical trial, tanezumab was injected every eight weeks in patients with moderate to severe hip or knee osteoarthritis who had failed acetaminophen (Tylenol®), NSAIDs and opioids.3 Patients taking tanezumab 5mg experienced significant improvement from baseline compared with placebo in measures of pain, physical function, and disease activity. Patients taking tanezumab 2.5 mg saw an improvement in pain and physical function, but not in measures of disease activity. While these results are encouraging, there are safety issues to be considered. A rapidly progressive form of osteoarthritis developed in 1.4% and 2.8% of patients in the tanezumab 2.5 mg and tanezumab 5 mg groups, respectively and none receiving placebo. There was also a higher rate of non-elective joint replacements in the tanezumab 5mg group. Additionally, there were more neurological side effects in the tanezumab groups than placebo, including tingling, reduced sensation, and carpal tunnel. A decision from the U.S. Food and Drug Administration (FDA) is expected in quarter two of 2021; in recent days, an FDA advisory committee has recommended against approval of tanezumab, concluding that the risks of the treatment don’t outweigh the benefits. Still, some patients say the risk is worth it. The FDA has yet to decide, but it usually follows the recommendations of its advisory panels. If approved, it’s expected that utilization will be limited by CVS until the product is reviewed by a Formulary Committee. A 2016 cost effectiveness analysis estimated the drug would be cost-effective at a price of less than or equal to $400 per dose4, but it’s important to remember this analysis was done before some of the clinical trials were completed.

Anticipated Launch: Second Quarter 2021 — if the FDA does not follow the recommendation of its advisory panel.

Impact: Moderate. Tanezumab’s novel mechanism of action will be appealing for patients who have failed many other treatments. There are 32.5 million people living with osteoarthritis in the U.S., and a growing percentage of those are in the moderate to severe category.

Price: Unknown but will almost certainly be more costly than NSAIDs and opioids.

Abrocitinib: Abrocitinib is a Janus Kinase 1 inhibitor (JAK1), the first of its kind to be approved for atopic dermatitis (eczema). However, JAK inhibitors are not an entirely new class of drugs. They have been used for conditions like rheumatoid arthritis, polycythemia vera and myelofibrosis for many years. Two doses of abrocitinib were studied in a clinical trial against placebo in patients with moderate to severe atopic dermatitis.5 Two measures of symptom severity, Investigator Global Response (IGA) and the Eczema Area and Severity Index (EASI), were used to determine the drug’s efficacy. IGA response was significantly higher in the abrocitinib 100mg and 200mg groups versus the placebo group (24% and 44% versus 8%, respectively). Similarly, the percentage of patients who experienced a 75% improvement in EASI score was significantly higher in the abrocitinib 100mg and 200mg groups versus the placebo group (40% and 63% versus 12%, respectively). Dupixent®, an injectable drug for atopic dermatitis and abrocitinib’s main competitor, has been shown in its own clinical trials to produce a 75% improvement in EASI score in 44-51% of patients.6 A head-to-head trial comparing Dupixent and abrocitinib has been completed but the results have yet to be published. Abrocitinib was generally well-tolerated in clinical trials, with nausea, headache, and cold symptoms as the most frequent side effects. Despite this encouraging data, some providers may be hesitant to jump on board, at least initially, due to safety concerns documented with other JAK inhibitors. An increased risk of cancer, blood clots and cardiovascular events has been found with JAK inhibitor use versus standard-of-therapy drugs in patients with rheumatoid arthritis.7 Dupixent® carries an elevated risk of inflammatory eye conditions like conjunctivitis and keratitis but is otherwise well tolerated. To stay competitive with other JAK inhibitors and with Dupixent®, abrocitinib would need to be priced in the range of $2,400 to $3,200 per month.

Anticipated Launch: Second Quarter 2021.

Impact: Moderate. It’s likely to replace Dupixent® in patients who have inadequate response. 3 million children and 6.6 million adults have moderate to severe atopic dermatitis in the U.S.

Price: Unknown but likely to be in the range of $2,400 to $3,200 per month.

Tralokinumab: Tralokinumab is an injectable monoclonal antibody that inhibits interleukin 13 (IL-13) and has been studied for use in patients with moderate to severe atopic dermatitis (eczema). Of the existing therapies for atopic dermatitis, it is most like Dupixent®. In two clinical trials for the drug, a 75% improvement in the EASI was achieved by 25% and 33.2% of patients on tralokinumab versus 12.7% and 11.4% with placebo at week 16.8 An IGA score of 0 or 1, signifying low disease activity, was achieved by 15.8% and 22.2% of patients on tralokinumab versus 7.1% and 10.9% of patients on placebo. In its own clinical trials, 44%-51% of Dupixent® users saw a 75% improvement in the EASI score; 36-38% of these patients achieved a score of 0 or 1 on the IGA.6 Tralokinumab was generally well tolerated in trials, with side effects like placebo in most categories; inflammatory eye conditions like conjunctivitis and keratitis have been a concern for Dupixent® users, and it appears those risks with tralokinumab may be slightly less. All things considered, tralokinumab’s efficacy data doesn’t appear as strong as Dupixent®’s, but it represents an additional option for patients who can’t tolerate Dupixent® and are uncomfortable with a JAK inhibitor such as abrocitinib. The price hasn’t been announced yet, but it will likely be priced equal to or slightly lower than Dupixent®, which costs $3,200 per month.

Anticipated Launch: Second Quarter 2021.

Impact: Low. Dupixent® is likely to remain the standard of care for patients who need a specialty biologic for treatment of atopic dermatitis. 3 million children and 6.6 million adults have moderate to severe atopic dermatitis in the U.S.

Price: Unknown but likely to be near $3,200 per month.

 

  1. Anthenelli RM, Benowitz NL, West R, et al. Neuropsychiatric safety and efficacy of varenicline, bupropion, and nicotine patch in smokers with and without psychiatric disorders (EAGLES): a double-blind, randomised, placebo-controlled clinical trial. Lancet. 2016;387(10037):2507-2520.
  2. Benli AR, Erturhan S, Oruc MA, Kalpakci P, Sunay D, Demirel Y. A comparison of the efficacy of varenicline and bupropion and an evaluation of the effect of the medications in the context of the smoking cessation programme.  Tob Induc Dis 2017; 15:10.
  3. Berenbaum F, Blanco FB, Guermazi A, et al. Subcutaneous tanezumab for osteoarthritis of the hip or knee: efficacy and safety results from a 24-week randomised phase III study with a 24-week follow-up period.  Ann Rheum Dis 2020 Jun; 79(6): 800-810.
  4. Losina E, Michl G, Collins JE, et al. Model-based evaluation of cost-effectiveness of nerve growth factor inhibitors in knee osteoarthritis: impact of drug cost, toxicity, and means of administration.  Osteoarthr Cartil 2016; 24(5): 776-785.
  5. Simpson EL, Sinclair R, Forman S, et al. Efficacy and safety of abrocitinib in adults and adolescents with moderate-to-severe atopic dermatitis (JADE MONO-1): a multicentre, double-blind, randomised, placebo-controlled, phase 3 trial.  Lancet 2020 Jul 25; 396(10246):  255-66.
  6. Dupixent (dupilumab) [package insert]. Tarrytown, NY: Regeneron Pharmaceuticals, Inc; 2021
  7. Pfizer Shares Co-Primary Endpoint Results from Post-Marketing Required Safety Study of XELJANZ® (tofacitinib) in Subjects with Rheumatoid Arthritis (RA).   Available at:  https://www.pfizer.com/news/press-release/press-release-detail/pfizer-shares-co-primary-endpoint-results-post-marketing
  8. Wollenberg A, Blauvelt A, Guttman-Yassky E, et al. Tralokinumab for moderate-to-severe atopic dermatitis: results from two 52-week, randomized, double-blind, multicentre, placebo-controlled phase III trials (ECZTRA 1 and ECZTRA 2).  Br J Dermatol 2021; 184: 437-449.