Currently Viewing:
Supplements Improving Provider and Patient Acceptance of Biosimilars in Treating Cancer: Clinical, Manufacturing, and Cost Considerations
The Complexities of Biosimilars and the Regulatory Approval Process
Steven Lucio, PharmD, BCPS
Currently Reading
Opportunities and Challenges in Biosimilar Uptake in Oncology
Carina Dolan, PharmD, BCOP
Posttest

Opportunities and Challenges in Biosimilar Uptake in Oncology

Carina Dolan, PharmD, BCOP
Another potential barrier to the clinical integration of biosimilars may be the temporal and financial investment required to make the distribution change from the current biologic to a biosimilar. It is important to take into consideration the fine details that participants in the supply chain, such as manufacturers, pharmacy benefit managers, and specialty pharmacies, have in place to encourage continued prescribing of the reference product.14

Finally, although there are now 10 approved biosimilar drugs, only 3 are currently on the market. These delays in launching the biosimilar products are a result of pending litigation from the reference drug manufacturer. This presents a challenge for the ability of the biosimilars to penetrate the market in a timely fashion. Furthermore, brand suppliers are bringing new products to the market by enhancing the original biologic, otherwise known as follow-on biologics or “biobetters.”31 These new molecular entities are altered versions of approved biologics designed to improve their method of administration, safety, efficacy, or manufacturing.32 All of these issues may limit the potential cost savings from biosimilar use in the next several years, although their use will likely increase over time due to supply and demand factors.33

The Economic Implications of Biosimilars in Cancer Therapy

Historically, when a generic drug enters the market, the cost is less than that of the brand manufacturer. However, payers should not expect this level of price differential when it comes to biologics and biosimilars, nor even the 50% price differential they had hoped for.31 There are several reasons for this, including the higher cost of bringing a biosimilar to market. This can cost more than $100 million and take 5 years or more compared with the $2 million to $5 million and 2 years required for a generic.33

Other barriers to lower pricing include complex, high-cost manufacturing processes; direct marketing to clinicians to share clinical data and highlight the efficacy and safety of the biosimilar compared with the original drug; development of a sales force in a new therapeutic arena; the need for phase 4 studies to demonstrate real-world safety and efficacy; and the likelihood that there may be a limited number of biosimilars in a given category.34

At the same time, rebates provided by pharmacy benefit managers and manufacturers that are tied to utilization of the reference drug may also mitigate any price reductions. Missing out on those rebates if patients are switched to biosimilars could make the reference drug much costlier, wiping out any savings from the biosimilar.31

A 2017 analysis from the RAND Corporation estimated that biosimilars would reduce direct spending on biologic drugs by $54 billion between 2017 and 2026, or about 3% of the total estimated biologic spending over the same period, with a range of $24 billion to $150 billion. The researchers cautioned, however, that the actual savings are dependent on industry, regulatory, prescriber, and insurer decisions, as well as potential future policy changes to strengthen the biosimilar market (Figure 2).6

As part of its analysis, RAND provided a case study on the uptake and cost savings of filgrastim-sndz and tbo-filgrastim. By the end of 2016, these 2 biosimilar-related products held a third of the total filgrastim market and were marketed at a 30% (tbo-filgrastim) and 45% (filgrastim-sndz) discount. RAND also noted that total spending on all 3 products (including filgrastim reference drug) dropped significantly between 2013 and 2016, suggesting the impact of the biosimilars. In addition, while the net price of filgrastim did not change during this time, both biosimilar-related drugs experienced large price decreases following their launch, likely due to competition in the marketplace, demonstrating that biosimilars could also increase access to more expensive drugs.6,35,36

A 2017 simulation analysis of the cost savings resulting from the use of filgrastim-sndz versus filgrastim on 20,000 patients with follicular lymphoma found a per-cycle cost savings between $327 and $915, depending on the length of the cycle, yielding a savings between $6.54 million (5-day cycle) and $18.3 million (14-day cycle). The authors estimated that the savings would generate expanded access to the biologic obinutuzumab, approved for relapsed/refractory follicular lymphoma and previously untreated chronic lymphocytic leukemia, to between 60 and 169 patients in a budget-neutral manner.37

The same analysis showed that switching patients from pegfilgrastim to filgrastim-sndz yielded savings of between $55.9 million for 5 days of treatment and $16.7 million for a 14-day cycle. The savings would expand access to obinutuzumab treatment for patients in a budget-neutral manner.37

New and Emerging Cancer Biosimilar Agents

Several oncologic biosimilars to trastuzumab, rituximab, cetuximab, and bevacizumab are in late-stage clinical trials (Table38-51).

Trastuzumab. The trastuzumab biosimilar CT-P6 demonstrated similar efficacy and safety in a head-to-head trial with trastuzumab (both combined with paclitaxel) in HER2-positive metastatic breast cancer (MBC) as well as in the neoadjuvant setting in women with early-stage breast cancer.38,39 The biosimilar BCD-022 also demonstrated similar efficacy and safety in the MBC setting.40 Another trastuzumab biosimilar candidate, SB3, was also studied in the neoadjuvant study in patients with early-stage breast cancer. It demonstrated equivalence based on pathologic clinical response rate, safety, pharmacokinetics, and immunogenicity.41

Rituximab. Several biosimilars are under investigation for rituximab, including CT-P10 in patients with follicular lymphoma. Early results from an ongoing randomized clinical trial in patients with late-stage disease demonstrated CT-P10’s similar efficacy, safety, and pharmacokinetic equivalence to rituximab.42 Meanwhile, the biosimilar BCD-020 demonstrated significant difference in overall relapse rate and safety compared with rituximab in 92 patients with follicular or marginal zone non-Hodgkin lymphoma.43 A third rituximab biosimilar, RTX-M83, demonstrated comparable efficacy to rituximab in terms of tumor response, pharmacokinetic profile, pharmacodynamic activity, safety, and immunogenicity in patients with previously untreated CD20+ diffuse large B-cell lymphoma.44

Bevacizumab. Bevacizumab biosimilar candidates include BCD-021, studied in patients with advanced nonsquamous non–small cell lung cancer (NSCLC) in combination with paclitaxel plus carboplatin. There were no significant differences in efficacy or safety between the biosimilar and the reference product.45 At least 5 other bevacizumab biosimilars are in late-stage clinical trials.46

Cetuximab. One of the first biosimilars to be studied against a drug other than the reference biologic, STI-001, was investigated in EGFR-expressing metastatic colorectal cancer patients in combination with irinotecan versus irinotecan alone. The combination therapy showed significant improvement compared with chemotherapy alone with an overall response rate of 32.9% versus 12.8%, a progression-free survival rate of 5.6 versus 3.2 months, and overall survival of 14.1 versus 13.4 months.47 The manufacturer also reported significantly fewer adverse events than in studies of the reference product, with no hypersensitive reaction compared with more than 10% of patients in the cetuximab trials. The manufacturer attributed the difference to a different production method. However, the results have not yet been published, only announced in a 2016 press release. Several other cetuximab biosimilars are in early development.48

Conclusions

As more patents begin to expire on oncologic biologics, the pace of biosimilar development in this therapeutic arena will pick up speed. At least 16 biosimilars are now in late-stage development and 2 are already approved (albeit not on the market as of March 2018). Their uptake in the oncology community, however, remains unclear. Challenges include physician and patient understanding of biosimilars versus biologics, particularly in terms of approval process; concerns over immunogenicity; pricing; interchangeability and substitution; cost; and supply chain issues. The option biosimilars offer, even at a 15% discount, will likely overcome these barriers as they move into the market and offer some promise for future treatments. 

Author affiliation: Director of Clinical Oncology and Pharmaceutical Outcomes, Center for Pharmacy Practice Excellence, Vizient, Irving, TX.
Funding source: This activity is supported by educational funding provided by Amgen Inc.
Author disclosure: Dr Dolan is an employee of Vizient in Irving, TX.
Authorship information: Concept and design, drafting of the manuscript, and critical revision of the manuscript for important intellectual content.
Address correspondence to: carina.dolan@vizientinc.com.
 
1. FDA-approved biosimilar products. FDA website. www.fda.gov/Drugs/DevelopmentApprovalProcess/HowDrugsareDevelopedandApproved/ApprovalApplications/TherapeuticBiologicApplications/Biosimilars/ucm580432.htm. Updated May 16, 2018. Accessed May 21, 2018.
2. Davio K. Scott Gottlieb: economics of biosimilar development are “currently unstable.” Center for Biosimilars. centerforbiosimilars.com/news/scott-gottlieb-economics-of-biosimilar-development-are-currently-unstable. Published March 7, 2018. Accessed March 13, 2018.
3. Jackson K, Nahata MC. Rising cost of anticancer medications in the United States. Ann Pharmacother. 2017;51(8):706-710. doi: 10.1177/1060028017702406.
4. Socinski MA, Curigliano G, Jacobs I, Gumbiner B, MacDonald J, Thomas D. Clinical considerations for the development of biosimilars in oncology. MAbs. 2015;7(2):286-293. doi: 10.1080/19420862.2015.1008346.
5. Nabhan C, Parsad S, Mato AR, Feinberg BA. Biosimilars in oncology in the United States: a review. JAMA Oncol. 2018;4(2):241-247. doi: 10.1001/jamaoncol.2017.2004.
6. Mulcahy AW, Hlávka JP, Case SR. Biosimilar cost savings in the United States: initial experience and future potential. RAND Corporation; rand.org/content/dam/rand/pubs/perspectives/PE200/PE264/RAND_PE264.pdf. Published 2017. Accessed March 10, 2018.
7. Rak Tkaczuk KH, Jacobs IA. Biosimilars in oncology: from development to clinical practice. Semin Oncol. 2014;41(suppl 3):S3-S12. doi: 10.1053/j.seminoncol.2014.03.008.
8. Molinari A, Gewanter H, Reilly M, Kennedy B, Charles D. SAT0570 biologics and biosimilars:
do physicians understand the differences? Ann Rheum Dis. 2016;75(suppl 2):875-876.
9. Camacho LH, Frost CP, Abella E, Morrow PK, Whittaker S. Biosimilars 101: considerations for U.S. oncologists in clinical practice. Cancer Med. 2014;3(4):889-899. doi: 10.1002/cam4.258.
10. D’Ambrosio J. Biosimilars are coming. Are you ready? Clarkston Consulting website.
clarkstonconsulting.com/insights/biosimilars-are-coming-are-you-ready. Published July 1, 2013. Accessed May 21, 2018.
11. Cohen H, Beydoun D, Chien D, et al. Awareness, knowledge, and perceptions of biosimilars among specialty physicians. Adv Ther. 2017;33(12):2160-2172.
12. North American Center for Continuing Medical Education (NACCME). 2013 biosimilars CME survey results—full report. NACCME website. naccme.com/2013-biosimilars-cme-survey-results-full-report. Accessed May 21, 2018.
13. Lyman GH, Balaban E, Diaz M, et al. American Society of Clinical Oncology statement: biosimilars in oncology. J Clin Oncol. 2018;36(12):1260-1265. doi: 10.1200/JCO.2017.77.4893.
14. Rifkin RM, Peck SR. Biosimilars: implications for clinical practice. J Oncol Pract. 2017;13(9_suppl):24s-31s. doi: 10.1200/JOP.2017.025734.
15. Prescribing biosimilar and interchangeable products. FDA website. www.fda.gov/Drugs/DevelopmentApprovalProcess/HowDrugsareDevelopedandApproved/ApprovalApplications/TherapeuticBiologicApplications/Biosimilars/ucm580430.htm#standards. Updated October 23, 2017. Accessed March 12, 2018.
16. Information for industry (biosimilars). FDA website. www.fda.gov/Drugs/DevelopmentApproval
Process/HowDrugsareDevelopedandApproved/ApprovalApplications/TherapeuticBiologicApplications/Biosimilars/ucm580433.htm#guidance. Updated October 23, 2017. Accessed May 22, 2018.
17. Brennan Z. FDA: interchangeable biosimilar approvals expected within 2 years. Regulatory Affairs Professional Society website. raps.org/news-articles/news-articles/2017/6/fda-interchangeable-biosimilar-approvals-expected-within-2-years. Published June 26, 2017. Accessed March 12, 2018.
18. Regulatory focus: state laws and legislation related to biologic medications and substitution of biosimilars. National Conference of State Legislatures website. ncsl.org/research/health/state-laws-and-legislation-related-to-biologic-medications-and-substitution-of-biosimilars.aspx. Published April 10, 2018. Accessed May 22, 2018.
19. Crespi-Lofton J, Skelton JB. The growing role of biologics and biosimilars in the United States: perspectives from the APhA Biologics and Biosimilars Stakeholder Conference. J Am Pharm Assoc. 2017;57(5):e15-e27. doi: 10.1016/j.japh.2017.05.014.
20. Cavallo J. Oncologists speak out against the high cost of cancer drugs. ASCO Post website. ascopost.com/issues/august-15-2013/oncologists-speak-out-against-the-high-cost-of-cancer-drugs.aspx. Published August 15, 2013. Accessed May 22, 2018.
21. Leading autoimmune patient advocacy group survey finds overwhelming majority of patients lack understanding of biosimilar drugs [news release]. East Detroit, IL: American Autoimmune Related Diseases Association; February 11, 2015. aarda.org/wp-content/uploads/2017/03/BiosimilarsWhitePaperPressRelease.pdf. Accessed May 22, 2018.
22. Xu J. Top health industry issues of 2016. issue 10: Enter the biosimilars. PricewaterhouseCoopers website. pwchk.com/en/people-and-organisation/hc-top-issues-10-jun2016.pdf. Published June 2016. Accessed March 14, 2018.
23. Part B costs. Official US government site for Medicare. medicare.gov/your-medicare-costs/part-b-costs/part-b-costs.html. Updated 2018. Accessed April 10, 2018.
24. Henry J. Kaiser Family Foundation. 2017 Employer Health Benefits Survey. kff.org/health-costs/report/2017-employer-health-benefits-survey. Published September 19, 2017. Accessed May 22, 2018.
25. Brill A. Payor stretegies to promote biosimilar utilization. Pharmaceutical Care Management Association website. pcmanet.org/wp-content/uploads/2016/08/mga-payor-strategies-for-biosimilars-white-paper-april-2016-2.pdf. Published April 2016. Accessed May 22, 2018.
26. Preidt R. Nearly 25 million U.S. workers now have high-deductible health plans. Health Day News for Healthier Living. consumer.healthday.com/public-health-information-30/misc-insurance-news-424/nearly-25-million-u-s-workers-now-have-high-deductible-health-plans-726334.html. Published September 15, 2017. Accessed November 1, 2017.
27. Chino F, Peppercorn JM, Rushing C, et al. Out-of-pocket costs, financial distress, and underinsurance in cancer care. JAMA Oncol. 2017;3(11):1582-1584. doi: 10.1001/jamaoncol.2017.2148.
28. Medicare Part B. Health Affairs website. healthaffairs.org/do/10.1377/hpb20171008.000171/full. Published August 10, 2017. Accessed April 10, 2018.
29. Part B biosimilar biological product payment and required modifiers. CMS website. cms.gov/Medicare/Medicare-Fee-for-Service-Part-B-Drugs/McrPartBDrugAvgSalesPrice/Part-B-Biosimilar-Biological-Product-Payment.html. Updated February 2, 2018. Accessed March 12, 2018.
30. Renwick MJ, Smolina K, Gladstone EJ, Weymann D, Morgan SG. Postmarket policy considerations for biosimilar oncology drugs. Lancet Oncol. 2016;17(1):e31-e38. doi: 10.1016/S1470-2045(15)00381-2.
31. Simmons-Stern N, Danosi C, Haber A, et al. The state of US biosimilars market access: payer perceptions of past, present, and future hurdles to adoption. Trinity Partners website. trinitypartners.com/files/5815/1638/4057/The_State_of_US_Biosimilars_Market_Access.pdf. Published January 2018. Accessed May 22, 2018.
32. Anour R. Biosimilars versus ‘biobetters’—a regulator’s perspective. GaBI J. 2014;3(4):166-167. doi: 10.5639/gabij.2014.0304.039.
33. Grabowski HG, Guha R, Salgado M. Regulatory and cost barriers are likely to limit biosimilar
development and expected savings in the near future. Health Aff (Millwood). 2014;33(6):1048-1057. doi: 10.1377/hlthaff.2013.0862.
34. Mestre-Ferrandiz J, Towse A, Berdud M. Biosimilars: how can payers get long-term savings? Pharmacoeconomics. 2016;34(6):609-616. doi: 10.1007/s40273-015-0380-x.
35. Chopra R, Lopes G. Improving access to cancer treatments: the role of biosimilars. J Glob Oncol. 2017;3(5):596-610. doi: 10.1200/JGO.2016.008607.
36. Monk BJ, Lammers PE, Cartwright T, Jacobs I. Barriers to the access of bevacizumab in patients with solid tumors and the potential impact of biosimilars: a physician survey. Pharmaceuticals (Basel). 2017;10(1). pi:E19. doi: 10.3390/ph10010019.
37. McBride A, et al. Expanded access to obinutuzumab from cost-savings generated by biosimilar filgrastim-sndz in the prophylaxis of chemotherapy-induced (febrile) neutropenia: US Simulation Study Paper presented at: ASH 59th Annual Meeting and Exposition; December 9-12, 2017; Atlanta, GA.
38. Im Y-H, Odarchenko P, Grecea D, et al. Double-blind, randomized, parallel group, phase III study to demonstrate equivalent efficacy and comparable safety of CT-P6 and trastuzumab, both in combination with paclitaxel, in patients with metastatic breast cancer (MBC) as first-line treatment. J Clin Oncol. 2013;31(15):629. doi: 10.1200/jco.2013.31.15_suppl.629.
39. Stebbing J, Baranau Y, Baryash V, et al. CT-P6 compared with reference trastuzumab for HER2-positive breast cancer: a randomised, double-blind, active-controlled, phase 3 equivalence trial. Lancet Oncol. 2017;18(7):917-928. doi: 10.1016/S1470-2045(17)30434-5.
40. Stenina MB, Ignatova E, Frolova MA, et al. Pharmacokinetics and safety of BCD-022, trastuzumab biosimilar candidate, compared to Herceptin in patients. J Clin Oncol. 2014;32(15_suppl):e11576. doi: 10.1200/jco.2014.32.15_suppl.e11576.
41. Pivot X, Bondarenko I, Nowecki Z, et al. Phase III, randomized, double-blind study comparing the
efficacy, safety, and immunogenicity of SB3 (trastuzumab biosimilar) and reference trastuzumab in patients treated with neoadjuvant therapy for human epidermal growth factor receptor 2-positive early breast cancer. J Clin Oncol. 2018;36(10):968-974. doi: 10.1200/JCO.2017.74.0126.
42. Kim WS, Buske C, Ogura M, et al. Efficacy, pharmacokinetics, and safety of the biosimilar CT-P10 compared with rituximab in patients with previously untreated advanced-stage follicular lymphoma: a randomised, double-blind, parallel-group, non-inferiority phase 3 trial. Lancet Haematol. 2017;4(8):e362-e373. doi: 10.1016/S2352-3026(17)30120-5.
43. Kaplanov K, Zaritskiy A, Alexeev S, et al. Key results of international randomized open-label clinical study of BCD-020 (rituximab biosimilar candidate) in patients with B-cell non-Hodgkin’s lymphoma. Blood. 2014;124(21):5467.
44. Candelaria M, et al. A randomized, double-blind, phase III study comparing proposed biosimilar rituximab (RTXM83) versus reference rituximab, both in combination with CHOP, in the first line treatment of patients with diffuse large B-cell lymphoma (DLBCL) Paper presented at: ASH 59th Annual Meeting and Exposition; Dec 9-12, 2017; Atlanta, GA.
45. Filon O, Orlov S, Burdaeva O, et al. Efficacy and safety of BCD-021, bevacizumab biosimilar
candidate, compared to Avastin: results of international multicenter randomized double blind phase III study in patients with advanced non-squamous NSCLC. J Clin Oncol. 2015;33(15_suppl):8057. doi: 10.1200/jco.2015.33.15_suppl.8057.
46. Cancer trials 2017. Search results. Clinicaltrials.gov. Accessed March 14, 2018.
47. Sorrento announces positive data from phase 3 studies of biosimilar antibodies, STI-001 and STI-002 [news release]. San Diego, CA: Sorrento Therapeutics, Inc. January 11, 2016. prnewswire.com/news-releases/sorrento-announces-positive-data-from-phase-3-studies-of-biosimilar-antibodies-sti-001-and-sti-002-300202054.html. Accessed May 22, 2018.
48. DiGrande S. Cetuximab biosimilars are on the horizon. Center for Biosimilars. centerforbiosimilars.com/news/cetuximab-biosimilars-are-on-the-horizon. Published January 25, 2018. Accessed March 13, 2018.
49. Celltrion and Teva announce BLA for rituximab biosimilar CT-P10. Center for Biosimilars website. centerforbiosimilars.com/news/celltrion-and-teva-announce-bla-for-rituximab-biosimilar-ctp10. Published June 29, 2017. Accessed May 22, 2018.
50. Jurczak W, Moreira I, Kanakasetty GB, et al. Rituximab biosimilar and reference rituximab in patients with previously untreated advanced follicular lymphoma (ASSIST-FL): primary results from a confirmatory phase 3, double-blind, randomised, controlled study. Lancet Haematol. 2017;4(8):e350-e361. doi: 10.1016/S2352-3026(17)30106-0.
51. Harris J. FDA accepts application for rituximab biosimilar. OncLive. onclive.com/web-exclusives/fda-accepts-application-for-rituximab-biosimilar. Published September 12, 2017. Accessed March 14, 2018.
 
PDF
 
Copyright AJMC 2006-2018 Clinical Care Targeted Communications Group, LLC. All Rights Reserved.
x
Welcome the the new and improved AJMC.com, the premier managed market network. Tell us about yourself so that we can serve you better.
Sign Up
×

Sign In

Not a member? Sign up now!