Genevieve Regal, PharmD, HC-MBA

In 2012, 9.7 million people worldwide received antiretroviral therapy (ART), representng an 11% increase from the previous year. ART is significantly contributing to the ongoing drop in new annual HIV infections around the world, which has resulted in improved life expectancy.

 With treatment advancements, HIV has evolved from a terminal illness to a manageable long-term chronic disease. Pharmacists are ideally positioned to provide a primary-line interface to patients with HIV. The expanding role of the pharmacist can significantly improve patient outcomes and ART results, and the integration of a pharmacist to an HIV care team can help to maximize ART adherence and drug resistance prevention and deliver HIV-focused medication therapy management (MTM) services.

The US National HIV/AIDS Strategy from HHS suggests that diversifying a support team’s skill set will strengthen the quality of care. Pharmacist integration into the HIV care team is based on patient accessibility and schedule flexibility. Patients have the flexibility to access pharmacist care at a time and place that is convenient; however, HIV clinics with set hours may present access challenges due to conflicting schedules. Community pharmacists provide easier access. Community pharmacists have demonstrated success in managing the medication needs of patients with chronic illness, leading to improvements in therapy adherence and drug resistance prevention. A 2007 evaluation of Medicare Part D recipients indicated that 90% of urban beneficiaries lived within 4 miles and 70% of rural beneficiaries lived within 15 miles of a community pharmacy.

With the rise in drug resistance, treatment options have become limited and require a more complex individualized patient care strategy. As drug resistance is linked to ART nonadherence, pharmacists understand treatment goals and the greater need for resistance prevention through improved adherence. The National HIV/AIDS Strategy has 4 primary goals:

1) Reduce the transmission of HIV infection.

2) Improve access to care and health outcomes for individuals infected with HIV.

3) Address health disparities and inequities among the HIV patient population.

4) Coordinate an effective national response to the epidemic.

Pharmacists understand the risk of resistance and complexities of ART dosing regimens. Regimens that contain at least 2 or 3 active drugs from ≥2 classes are recommended for virologic suppression.

 If a regimen fails, those active drugs can no longer be used due to potential resistance. Therefore, the choices available for a new 2-drug regimen become limited. Treatment plans are the same for both treatment-experienced and treatment-naiÌˆve patients, with the clinical end point being viral suppression while enabling immune recovery and minimizing adverse effects. Successful viral suppression will depend upon the adherence, safety, and tolerability of the chosen regimen.

 ART is essential to sustain viral suppression, reduce HIV-associated morbidity, prolong survival, and reduce HIV transmission. Pharmacist counseling and education improves medication adherence, which is key to reaching the clinical goals of patients with HIV.

In several well-documented studies, pharmacists improved ART adherence in patients with HIV. In a US Department of Veterans Affairs Medical Center adherence study, the results demonstrated a 10% increase in adherence associated with a viral load decrease.

 The Christiana Care Health System in Delaware also reported that patients who attended a pharmacist-led medication adherence clinic and at least 1 educational session from a clinical pharmacist had a statistically significant decrease in viral load 6 and 12 months after initiating therapy compared with patients who did not attend the clinic.

 Baseline CD4-positive (CD4+) T-lymphocyte counts and viral load data were similar for both groups.

In 2005, the California Department of Health Care Services developed a pilot program to evaluate the effectiveness of community-based, financially compensated, pharmacist-led MTM services for patients with HIV/AIDS. Ten pharmacies were selected to participate in the study, and 2234 patients used the pilot services. These services were individualized and patient specific, with pharmacists providing face-to-face services to the patients or, in limited circumstances, the patient’s caregiver. Following the first year of the program, study participants reported higher medication adherence rates, fewer excess fills, and fewer contraindicated regimens compared with patients not in the program. In addition, patients in the program remained on a single type of ART regimen throughout the study year, decreasing the likelihood of developing drug resistance and enhancing the ability to maintain their health over longer periods of time.

A 3-year follow-up to this pilot program was reported in 2011. The evaluation showed a continuation of results in which patients reported higher adherence rates to ART, fewer excess fills, and fewer contraindicated regimens. Patients remained on a single type of ART regimen each year of the study, indicating the decreasing likelihood of developing drug resistance and preserving therapeutic options in the future.

By the same token, HIV has evolved into a manageable chronic disease and has created an even greater need for HIV-focused MTM services. The results of 1 study showed MTM services resulted in a 31% reduction in total health expenditures per patient, from $11,965 to $8197, and a 14% increase clinical goals achieved.

 A comprehensive medication review should start immediately with ART initiation. Pharmacist counseling of patients with HIV includes several key aspects: an evaluation to ensure appropriate dosage, patient administration counseling, ART adherence education, medication interactions, and possible adverse effect management. If lab data are available, monitoring of CD4+ cell counts and HIV RNA viral load could also be reviewed.

Through ongoing quarterly targeted medication counseling follow-up sessions, the pharmacist may identify ART noncompliance. They also provide routine communications back to the provider and the entire care team, which eases that burden on the patient. Adequate patient education, drug-focused expertise, and care coordination are essential for the overall MTM model. A true collaborative environment focused on the care of patients with HIV is vital to the success of any MTM program. Treatment goals are focused on early diagnosis, engagement, and integration of the patient into a comprehensive care program, retention of the patient in the program, and providing access to ART. With the US population of patients with HIV growing annually, there will be an ongoing need for comprehensive supportive care, and pharmacists can help meet this growing need by providing specialized MTM to these patients.

		World Health Organization (WHO). (2013). Global update on HIV treatment 2013: Results, Impact and Opportunities. Retrieved from 

http://www.who.int/hiv/pub/progressreports/update2013/en/

		Kauffman, Y., Nair, V., Herist, K., Thomas, V., & Weidle, P. J. (2012). HIV medication therapy management services in community pharmacies. Journal of the American Pharmacists Association. American Pharmacists Association. 

		National HIV/AIDS Strategy for the United States: Updated to 2020, Accessed at https://www.hiv.gov/federal-response/national-hiv-aids-strategy/nhas-update, October 1, 2018

		Cihlar, T., & Fordyce, M. (2016). Current status and prospects of HIV treatment. 

https://doi.org/10.1016/j.coviro.2016.03.004

		Grossberg R, Zhang Y, Gross R. A time-to-prescription-refill measure of antiretroviral adherence predicted changes in viral load in HIV. J Clin Epidemiol. 2004;57(10):1107-10.

		Cantwell-McNelis K, James CW. Role of clinical pharmacists in outpatient HIV clinics. Am J Health Syst Pharm. 2002;59(5):447-52.

		Hirsch, J. D., Rosenquist, A., Best, B. M., Miller, T. A., & Gilmer, T. P. (2009). Evaluation of the First Year of a Pilot Program in Community Pharmacy: HIV/AIDS Medication Therapy Management for Medi-Cal Beneficiaries. 

https://doi.org/10.18553/jmcp.2009.15.1.32

		Hirsch, J. D., Gonzales, M., Rosenquist, A., Miller, T. A., Gilmer, T. P., & Best, B. M. (2011). Antiretroviral Therapy Adherence, Medication Use, and Health Care Costs During 3 Years of a Community Pharmacy Medication Therapy Management Program for Medi-Cal Beneficiaries with HIV/AIDS. 

https://doi.org/10.18553/jmcp.2011.17.3.213

		Isetts BJ, Schondelmeyer SW. Clinical and economic outcomes of medication therapy management services: The Minnesota experience. J Am Pharm Assoc. 2008;48:203-11

Articles

Through ongoing quarterly targeted medication counseling follow-up sessions, the pharmacist may identify ART noncompliance.

The Pharmacistâ€™s Role in Maximizing HIV Antiretroviral Therapy

On August 23, 2018, the FDA approved lanadelumab-flyo (Takhzyro; Shire) for the prophylaxis treatment and prevention of hereditary angioedema (HAE) in patients 12 years or older. Lanadelumab-flyo calls for less frequent dosages relative to current treatment options of once or twice monthly and is poised to reduce acute attack treatment utilization.

HAE is a rare genetic disorder characterized by repeated extreme swelling of the arms, face, feet, hands, gastrointestinal tract, and upper airways. It can be a debilitating disease that negatively affects work, school, and travel. Airway swelling and respiratory obstruction associated with HAE are potentially life-threatening due to asphyxiation. Associated HAE gastrointestinal tract swelling cases present as severe abdominal pain, nausea, and vomiting.

Occurring in approximately 1 in 10,000 to 50,000 individuals, children have a 50% chance of genetically inheriting HAE; however, 25% of HAE cases are linked to spontaneous genetic mutations. There are 3 types of HAE, none of which respond to antihistamine or corticosteroid therapy. In types 1 and 2 HAE, patients have a genetic defect that results in the loss of C1-inhibitor control and produces characteristic swelling. Type 1 HAE is characterized by low C1-inhibitor levels due to gene defects on chromosome 11. Type 2 HAE is characterized by normal to low C1-inhibitor levels, and the inhibitors that are present are dysfunctional. Type 3 HAE research is ongoing, but the type has been found to be characterized by normal C1-inhibitor levels and function.

Lanadelumab-flyo is a fully human recombinant nonplasma-derived monoclonal antibody created in recombinant Chinese hamster ovary cells, and it inhibits plasma kallikrein. Plasma kallikrein is a protease that splits high-molecular—weight kininogen to produce a cleaved high-molecular–weight kininogen and bradykinin. The inhibition of plasma kallikrein reduces excess bradykinin production in patients with HAE. Bradykinin acts as a vasodilator that increases vascular permeability, leading to the characteristic HAE swelling and pain.

Lanadelumab-flyo provides concentration-dependent inhibition of plasma kallikrein and is dose proportional in the therapeutic dose range after subcutaneous (SC) administration. The elimination half-life is reached in 14 days, with peak plasma concentrations achieved at 5 days. The steady state concentrations are achieved at 70 days, with mean accumulation ratios of approximately 1.44, 1.42, and 2.43 for study dosing regimens of 150 mg every 4 weeks, 300 mg every 4 weeks, and 300 mg every 2 weeks, respectively. No significant or clinically meaningful differences were found during population pharmacokinetic analyses of age, gender and race. Clearance and volume of distribution fluctuated according to body weight; however, the differences were not clinically significant. Dosage adjustments were not recommended based on age, gender, race, or body weight. The coadministration of HAE acute attack rescue medications, plasma-derived and recombinant C1-INH, showed no changes in clearance and volume of distribution.

Lanadelumab-flyo’s suggested starting dose is 300 mg every 2 weeks. In well-controlled or attack-free patients, for at least 6 months, an extended dosing interval of 300 mg every 4 weeks may be more appropriate for some patients. No dosage adjustments are required for renal impairment.

Lanadelumab-flyo is available as a 300-mg/2 mL (150 mg/mL) single-dose vial solution, which should appear clear, slightly opalescent, colorless, or slightly yellow. No additional reconstitution, preparation, or dilution is necessary. The vial should not be used if the solution appears discolored or has visible particles, and the vial temperature should be allowed to normalize to room temperature prior to SC injection. Prescribing information recommends the drug be administered within 2 hours of dose syringe preparation. If refrigerated, it must be used within 8 hours of the dose syringe preparation.

For SC administration only, lanadelumab-flyo should be self-administered or administered by a caregiver. The prescribed dosage should be withdrawn from the vial using an 18-gauge needle and syringe. Using aseptic procedure, the needle should be changed to a 27-gauge, half-inch needle for SC administration into the abdomen, thigh, or upper arm. Unused portions of the drug remaining in the vial should be discarded after administration of the prescribed dose.

With a longer half-life than current prophylactic HAE treatments, lanadelumab-flyo data have been shown to reduce HAE attack incidence for longer intervals. It offers less frequent dosages relative to current treatments of every 2 or 4 weeks and is poised to reduce acute attack treatment utilization. Dosing intervals will be based on individual patient history, severity and frequency of attacks, and prescriber comfort level related to extending the dosing interval. Existing treatments require more frequent administration, which includes self-administered injectables for acute attacks or biweekly short acting intravenous infusions.

Reduced HAE attacks improve patient quality of life and the medication management burden. Lanadelumab-flyo should be used as a long-acting prophylaxis HAE treatment, while existing medications should be reserved for acute attack on-demand treatment.

“The data on lanadelumab continue to demonstrate the importance of controlling plasma kallikrein activity, which is chronically uncontrolled in those living with HAE, even between attacks,” Marc Riedl, MD, said in a Shire press release.

Existing HAE treatments are costly and present financial challenges for payers. According to a recent study by Prime Therapeutics, the average yearly total cost of care was $409,925 per person. Ninety-seven percent ($395,507) of these costs are due to medications. The study reviewed emergency department visits, hospital visits, medication use, and total cost of care data. For patients treated with mul- tiple HAE medications, the average cost was more than $1 million per person. Treatment of multiple family members with HAE amplifies costs into the multimillions. However, lanadelumab-flyo is poised to reduce attack frequency and lower costly acute attack medication utilization. As a result, acute attack HAE drug utilization may be reduced.

Given the promising clinical efficacy data and reduced dosing intervals compared with existing treatments, lanadelumab-flyo is poised to be added to most pharmacy benefit manager (PBM) formularies. Average wholesale price data (AWP) are speculated to be $26,484 for each 2-mL vial, with an approximate annual cost of $688,584, excluding rebate or contractual PBM discounts. In comparison, the AWP for the complement C1 esterase inhibitor, Cinryze, is approximately $686,400 per year, while Haegarda has an annual AWP of $586,560, depending on weight-based dosing.

Competitor HAE prophylaxis products use rebates to offset the clinical advantages of lanadelumab-flyo. As market competition increases between prophylaxis products, PBM rebate values will increase within the drug class. Rebates or contractual PBM discounts are excluded from the above AWP costs.

The HELP study was a phase 3 international, randomized, multicenter, parallel-group, double-blind, placebo-controlled trial that lasted 26 weeks. As the largest HAE prevention study to date, the frequency of confirmed angioedema attack episodes in the lanadelumab versus placebo treatment groups was the primary efficacy endpoint. Study enrollment included type 1 or 2 HAE adult and adolescent patients 12 years or older (N = 125) who experienced 1 confirmed attack per month.

Randomized study enrollees were placed into 4 treatment groups: placebo, lanadelumab-flyo SC 300 mg every 2 weeks, lanadelumab-flyo SC 300 mg every 4 weeks, or lanadelumab-flyo SC 150 mg every 4 weeks. Patients in the lanadelumab-flyo treatment arms showed clinically meaningful and statistically significant drops in HAE attack rates. Compared with the placebo group, the 3 lanadelumab-flyo treatment arms reduced the number of HAE attacks by 76%, 73%, and 87%, respectively. Patients previously treated or currently taking C1 inhibitors were randomized into the placebo treatment group and the lanadelumab-flyo groups. Among the pretreated C1-inhibitor patients, the number of HAE attacks requiring acute treatment were reduced by 81%, 74%, and 87%, respectively, in the lanadelumab-flyo treatment arms.

As part of an uncontrolled, unblinded, open-label extension study, all patients who completed the HELP study were eligible to enroll and end points were investigative. The researchers administered 212 patients a starting dose of 300-mg lanadelumab-flyo. For patients previously treated in the 300-mg every 2 weeks dosing arm, results showed that 80% did not have an attack 4 weeks post dose.

According to the prescribing information, lanadelumab-flyo has no contraindications. The most common adverse effects include injection-site reactions (44%), upper respiratory infections (24%), headache (18%), rash (6%), myalgia (4%), dizziness (5%), and diarrhea (4%). Lanadelumab-flyo showed no effects on QT/QTc interval prolongation. Hypersensitivity reactions have been observed in lanadelumab-flyo.

Genevieve Regal is Clinical Pharmacy Consultant for Confidio, a technology enabled pharmacy benefit consulting firm serving millions of members nationally. As a Confidio Clinical Consultant, Genevieve supports Health Plans, Employers, and PBMs in clinical strategies and formulary cost management. Genevieve Regal, PharmD, HC-MBA, received her Doctor of Pharmacy from the Philadelphia College of Pharmacy, University of the Sciences and graduated Summa Cum Laude from George Washington University with a Healthcare Master of Business Administration Degree. Genevieve has 13 years pharmacy leadership experience in Medicare Part D plan administration, quality improvement, CMS Compliance, Program Audits, Sanction Remediation, Part D Best Practices, MTM & Pharmacy Operations. For more information please visit: www.confidio.com or to reach the author, please email her at 

On August 23, 2018, the FDA approved lanadelumab-flyo (Takhzyro; Shire) for the prophylaxis treatment and prevention of hereditary angioedema (HAE) in patients 12 years or older.

Takhzyro for Hereditary Angioedema

In 2017, biosimilars generated $3 billion worldwide in revenue and present growing market competition to the specialty biotech market. Escalating specialty drug costs present a challenge for many employers who struggle to balance health care spend with business financial livelihood.

Based on 2017 FDA research, the delayed market launch of nine 

 represented $4.5 billion in potential savings. As part of the FDA Biosimilar Action Plan, biosimilar drugs are poised to offer a solution that could help deliver significant cost advantages without compromising therapeutic efficacy, safety, or quality.   

Biosimilars are biologic drugs that are highly similar in structure and function to existing FDA approved reference drugs. With fully established FDA safety and efficacy data, reference drugs are used as the benchmark to which biosimilars are compared to.

For example, Neupogen is the reference drug for both biosimilar products Zarxio and Granix. Biosimilars must demonstrate no clinically meaningful efficacy differences and equal safety to gain FDA approval.

Read more about Neupogen's FDA approval here. 

Biosimilars should not be viewed as generic drugs, but rather an alternative form of brand medications that would usually be categorized as specialty.

“Biosimilars can provide greater access to treatment options for patients, increasing competition and potentially lowering costs,” Leah Christl, PhD, associate director for therapeutic biologics at the Office of New Drugs in the FDA Center for Drug Evaluation and Research.

As part of the President Donald Trump’s efforts to reduce drug costs, the FDA has released a plan to expedite the approval and market launch of biosimilars.

FDA Commissioner Scott Gottlieb, MD, said the agency will “work with the Federal Trade Commission to stop ‘gaming tactics’ like piling up patents to extend the commercial dominance of brand-name medicines.” 

Many biosimilars gain FDA approval but few are available on the market. Once FDA-approved, biosimilar products face an extended period between the approval and product market launch. This is due to the lengthy reference manufacturing patent review process that delays the number of biosimilars available for prescribing.

Dr. Gottlieb condemned reference manufacturer maneuvers to delay biosimilars market launch, saying, “We’re not going to play regulatory Whac-a-Mole with companies trying to unfairly delay or derail the entry of biosimilar competitors…we’re not going to wait a decade or more for robust biosimilar competition to emerge.”

Currently, biosimilars are not interchangeable with reference products, which further delays the prescribing and dispensing process. The Federal Trade Commission (FTC) requested the FDA release a statement allowing biosimilars to be automatically substituted.

The FTC said in a statement, “Experience with generic drugs teaches that automatic substitution is crucial for successful generic drug entry, market acceptance, and consumer savings.”

Automatic substitution would increase market access, drive costs down, and improve affordable patient access.

Biosimilars currently offer significant savings of 10% to 35% over reference drugs. For example, the reference drug Remicade treats inflammatory conditions such as rheumatoid arthritis or psoriasis. Specialty inflammatory drug expenditures have high utilization trends and accounted for 39% of the top 5 specialty products, according to Express Script data.

Remicade costs between $31,753 and $52,922 per year for an average weight American male. Biosimilars Renflexis and Inflectra offer 19% to 35% average wholesale price savings over the reference drug Remicade for a total savings of between $11,268 and $18,780 per year per patient. Likewise, Zarxio and Granix, both biosimilars of reference drug Neupogen, offer savings between 10% and 17%.

Savings would be amplified for all specialty patients if more biosimilars were available on the market, which is a savings value that is quite significant for payers and self-funded employers. With specialty drug costs predicted to be $6300 per claim by 2020—a surge that increased claim costs by 379% from the previous decade&mdash;biosimilars provide greater market competition and less expensive specialty drug therapy choices.

Most manufacturers and pharmacy benefit managers (PBM) generally will exclude biosimilars from specialty rebate guarantees. Consequently, biosimilar costs turn into a numbers game between manufactures, PBMs, and employers.

One alternative solution would allow PBMs to drive cost competition by incorporating biosimilars into formulary utilization management criteria. Step therapy has been proven effective in saving 2.3% of total drug spend. 

The proposal would allow biosimilar products to serve as a formulary step 1 criteria, requiring patients to try and fail lower cost, safe, and clinically equivalent therapies before coverage of more expensive medications. By adding to step therapy criteria, PBMs will promote biosimilar education and awareness in the medical community, which would continue to drive utilization.

Employers need strategies to contain specialty prescription costs. Step therapy programs have a proven history of success with biosimilars regulating costs and reducing clinical risks. Coupled with FDA plans to continue approval and market launch, greater biosimilar market penetration would help to increase competition and lower costs without compromising quality, efficacy, or patient safety.

Related Coverage: A Case for Biosimilar Use: 5 Things You Need to Know

As a Confidio Clinical Consultant, Genevieve supports Health Plans, Employers, and PBMs in clinical strategies and formulary cost management. Genevieve Regal, PharmD, HC-MBA, received her Doctor of Pharmacy from the Philadelphia College of Pharmacy, University of the Sciences and graduated Summa Cum Laude from George Washington University with a Healthcare Master of Business Administration Degree. Genevieve has 13 years pharmacy leadership experience in Medicare Part D plan administration, quality improvement, CMS Compliance, Program Audits, Sanction Remediation, Part D Best Practices, MTM & Pharmacy Operations. For questions or comments, Genevieve can be reached at 

FiercePharma. (2018). Retrieved from https://www.fiercepharma.com/: https://www.fiercepharma.com/

BusinessWire. (2014, December 23). FDA Approves Teva’s GRANIX® (tbo-filgrastim) Injection for Self-Administration. Retrieved from www.businesswire.com: https://www.businesswire.com/news/home/20141223005107/en/FDA-Approves-Teva’s-GRANIX®-tbo-filgrastim-Injection-Self-Administration

CMS Office of Actuary. (2018). CMS Office of the Actuary releases 2017-2026 Projections of National Health Expenditures. Retrieved from CMS.gov: https://www.cms.gov/Newsroom/MediaReleaseDatabase/Press-releases/2018-Press-releases-items/2018-02-14.html

Department of Health and Human Services. (2018). National Health Expenditure Projections 2017-202 - Research-Statistics-Data-and-Systems. Retrieved from CMS.gov: https://www.cms.gov/Research-Statistics-Data-and-Systems/Statistics-Trends-and-Reports/NationalHealthExpendData/Downloads/ForecastSummary.pdf

Edney, A. (2018, July 18). Drugmakers Game the Patent System and Reap Billions, FDA Says. Retrieved from www.bloomberg.com: https://www.bloomberg.com/news/articles/2018-07-18/fda-blasts-drugmakers-thwarting-competition-on-costly-biologics

Express Scripts Holding Company. (2018, July). Express Scripts Drug Trend Report. Retrieved from express-scripts.com: http://lab.express-scripts.com/lab/drug-trend-report

IQVIA. (2018, Jul1). IQVIA Institute for Human Data Science Study: 10 Predictions for Innovation, Spending Drivers and Societal Value of Medicines that Will Transform Global Healthcare in 2018 and Beyond. Retrieved from https://www.iqvia.com/en/newsroom/2018/03/iqvia-institute-for-human-data-science-study-10-predictions-for-innovation: https://www.iqvia.com/en/newsroom/2018/03/iqvia-institute-for-human-data-science-study-10-predictions-for-innovation

James, D. (2018, April 23). Specialty Drugs Power Growth in Pharmacy Benefit Spend. Retrieved from specialtypharmacytimes.com: https://www.specialtypharmacytimes.com/news/specialty-drugs-power-growth-in-pharmacy-benefit-spend

Motheral, B. e. (2004, January). Plan-Sponsor Savings and Member Experience with Point-of-Service Prescription Step Therapy. AJMC. Retrieved from https://www.pcmanet.org: https://www.pcmanet.org/wp-content/uploads/2016/08/visante-pbm-savings-feb-2016.pdf

Rabah Kamal and Cynthia Cox Kaiser Family Foundation. (2017, December 17). Express Scripts per-member-per-year spending, top 5 specialty therapy classes, 2016. Retrieved from www.healthsystemtracker.org: https://www.healthsystemtracker.org/chart-collection/recent-forecasted-trends-prescription-drug-spending/#item-medications-inflammatory-conditions-multiple-sclerosis-topped-specialty-drug-spending-2016_2017

Thomas M. Burton . (2018, July 18). FDA Unveils Effort to Get ‘Biosimilar’ Drugs on the Market Faster . Retrieved from www.wsj.com: https://www.wsj.com/articles/fda-unveils-effort-to-get-biosimilar-drugs-on-the-market-faster-1531937491

U.S. Food and Drug Administration. (2018, May). Biosimilar and Interchangeable Products. Retrieved from FDA.gov: https://www.fda.gov/Drugs/DevelopmentApprovalProcess/HowDrugsareDevelopedandApproved/ApprovalApplications/TherapeuticBiologicApplications/Biosimilars/ucm580419.htm

U.S. Food and Drug Administration. (2018). Biosimilar Product Information FDA-Approved Biosimilar Products. Retrieved from FDA.gov: https://www.fda.gov/Drugs/DevelopmentApprovalProcess/HowDrugsareDevelopedandApproved/ApprovalApplications/TherapeuticBiologicApplications/Biosimilars/ucm580432.htm

U.S. Food and Drug Administration. (2018). Purple Book: Lists of Licensed Biological Products with Reference Product Exclusivity and Biosimilarity or Interchangeability Evaluations. Retrieved from

FDA.gov: https://www.fda.gov/drugs/developmentapprovalprocess/howdrugsaredevelopedandapproved/approvalapplications/therapeuticbiologicapplications/biosimilars/ucm411418.htm

U.S. Food and Drug Administration. (n.d.). Biosimilars. Retrieved from FDA.gov: https://www.fda.gov/drugs/developmentapprovalprocess/howdrugsaredevelopedandapproved/approvalapplications/therapeuticbiologicapplications/biosimilars/default.htm

Based on 2017 FDA research, the delayed market launch of nine biosimilars represented $4.5 billion in potential savings.