Weighing The Potential Of Humira Biosimilars In The U.S. — Expected Winners And Losers

This is the second article in a two-part series exploring the anticipated competitive landscape for adalimumab biosimilars  following their U.S. launch in 2023. Part 1 looked at the unique competitive dynamics characterizing the adalimumab biosimilar market and highlighted some of the key drivers and barriers that biosimilar producers might face in claiming market share from AbbVie’s Humira. In this part, we evaluate the potential for individual adalimumab biosimilar products, comparing and contrasting the agents based on a number of important factors, including order of market entry, company resources and reputation, and product characteristics.

Order Of Market Entry

The first factor that will likely give certain adalimumab biosimilars an edge over others is their order of market entry. As described in more detail in Part 1 of this article series, the 2023 lineup of adalimumab biosimilar launches resulted from a cascade of settlements reached between AbbVie and biosimilar producers.  Of the eight biosimilars slated to launch, Amgen was granted the first slot and will launch Amjevita starting Jan. 31, 2023. As the next biosimilar to launch, Samsung Bioepis/Merck’s Hadlima, will not enter the market until the end of June, so Amjevita will have a five-month head start on its fellow biosimilar competitor. GlobalData believes that if Amgen is bold and chooses to offer aggressive discounts from the start — 30 percent or more — the company could win the attention of payers and potentially siphon away significant patient share from Humira before the entry of its biosimilar competitors. The remaining six biosimilar agents are likely at a disadvantage as they all will be launching in close succession during the second half of the year.

Company Resources And Reputation

In addition to order of launch, GlobalData believes that adalimumab biosimilar competition in the U.S. will be largely driven by the size of the company offering the biosimilar and, thus, the resources available for marketing, distribution, and patient support. Companies with higher U.S. revenues and more diverse portfolios may be able to offer adalimumab biosimilar products at steeper discounts and may also be able to orchestrate more favorable contracting agreements with payers, leveraging discounts on high-volume drugs in their portfolios to secure better coverage and access for their biosimilar products. With $23.9 billion in U.S. revenues in 2019, AbbVie’s U.S. market size is roughly similar to those of Pfizer, Merck, Amgen, and Novartis. As such, biosimilar products coming from slightly smaller companies, like Mylan’s Hulio and BI’s Cyltezo, may have a harder time competing.

Beyond having financial flexibility and powerful portfolios, there are other reasons that biosimilars from larger companies will likely outperform those from smaller ones. Key opinion leaders (KOLs) and payers interviewed by GlobalData asserted that beyond proven safety and efficacy, the reputation of the manufacturer and the expected supply stability are the most important features determining the competitiveness of a biosimilar. In particular, large firms with prior experience in the inflammatory disease market, like Pfizer, Merck, Amgen, and Novartis, will likely benefit from brand recognition and trust within the space. Additionally, these companies may be better equipped to provide robust educational and marketing services to physicians and patients, as well as to organize additional services typical for biologics, such as nurse administration services and co-pay support. KOLs and payers interviewed by GlobalData agreed that the availability of these support services would be crucial to choosing one biosimilar product over another.

Product Characteristics

Another potential defining factor between adalimumab biosimilar products is the availability of specialty doses and reduced-pain formulations. Beyond the typical 40 mg dose, Humira is available at 10 mg and 20 mg doses for the treatment of certain pediatric patient groups and 80 mg doses for use in indications requiring loading doses, such as Crohn’s disease and ulcerative colitis. Based on the most recent FDA labels, Pfizer’s Abrilada is the only agent having both 10 mg and 20 mg doses available, while Mylan’s Hulio, BI’s Cyltezo, and Amgen’s Amjevita have a 20 mg dose available; none offer the 80 mg dose.  

Although no biosimilars meet all the criteria for Humira’s new citrate-free, low-volume, smaller needle formulation, which was designed to reduce injection site pain, Amjevita, Cyltezo, Hulio, and Abrilada do use a citrate-free formulation and Hadlima, Hulio, Abrilada, and Amjevita’s prefilled syringes use a smaller 29G needle. Interestingly, data from a recent real-world study performed in the U.K. suggest that patients may actually be more likely to continue treatment with an adalimumab biosimilar if the biosimilar uses a citrate-free buffer. In the study, patients switching from citrate-free Humira to a citrate-free adalimumab biosimilar had a significantly lower rate of “switch failure” — i.e., patients wanting or needing to return to Humira or try another biosimilar — compared to patients who switched to a citrate-buffered biosimilar (2 percent vs. 8 percent; p=0.006).¹⁵ Among the 45 cases of switch failure following treatment with a citrate-buffered adalimumab biosimilar, 48 percent were deemed due to disease flare and 44 percent due to injection site pain or reaction. Thus, differences in formulation could prove to be another important factor in determining biosimilar uptake.

How Do Adalimumab Biosimilars Stack Up?

Taken together, Amgen’s Amjevita, Merck/Samsung Bioepis’ Hadlima, Novartis/Sandoz’s Hyrimoz, and Pfizer’s Abrilada appear to be some of the most promising adalimumab biosimilar products. All four companies have ample resources, experience with biosimilars, and potent U.S. market share across indications, as well as experience manufacturing, marketing, and providing support for products targeting autoimmune diseases. Pfizer’s Abrilada comes the closest to Humira’s current offering of doses and formulations, with 10 mg, 20 mg, and 40 mg doses, a citrate-free formulation, and a 29G needle. The major strike against Pfizer’s competitive position is that it is slated to launch second-to-last among currently approved biosimilars.

Out of the products that have already achieved FDA approval, those that stand out slightly less include Mylan’s Hulio and BI’s Cyltezo. Mylan has extensive experience in marketing generic and biosimilar products and offers a citrate-free adalimumab biosimilar with a smaller gauge needle, but the company is a lot smaller than many of the other biosimilar players. This may make it difficult to compete. Regarding Cyltezo, although BI is a highly respected company, it has a smaller U.S. portfolio than most competitors, less experience in the biosimilar and autoimmune field, and its product utilizes the older style of adalimumab delivery. Finally, when evaluating the two adalimumab biosimilars still awaiting FDA approval, Fresenius Kabi’s MSB11022 definitely has the upper hand over Coherus BioSciences’ CHS-1420; MSB11022 has secured an earlier U.S. launch date with AbbVie (by about three months) and has been successful thus far in the European market (sold under the name Idacio). When compared to the rest of the U.S. adalimumab biosimilar market, both of these companies’ products are likely to come up short. Not only do the companies lack a strong presence in the U.S. market, but their products are some of the last to launch in 2023, making it very difficult for them to compete.

Conclusions

2023 will certainly be an interesting year for biosimilars: In the span of 12 months, eight adalimumab biosimilar products could enter the U.S. market and begin a fiercely competitive battle for Humira market share. Although AbbVie is a pharmaceutical powerhouse and has used an array of life cycle management strategies to defend its life-blood drug, evidence from Europe suggests that aggressive discounting by adalimumab biosimilar producers was able to make a substantial dent in Humira’s market share.  Regulations favoring biosimilar use are not as supportive in the U.S. as they are in Europe, but the potential for major cost savings is likely to shake up the status quo among payers. On top of the potential for deep discounts, many of the adalimumab biosimilar agents set to launch in 2023 are marketed by other giants of the pharmaceutical industry, like Pfizer, Merck, Amgen, and Novartis, companies with strong reputations and ample resources. With these different factors considered together, payers and physicians may be willing to give adalimumab biosimilars a try.  Thus, while it is unlikely that uptake of adalimumab biosimilars will be as explosive as it was in Europe, the impact of these agents on the U.S. market should not be underestimated.

References

1. https://www.amgen.com/media/news-releases/2017/09/amgen-and-abbvie-agree-to-settlement-allowing-commercialization-of-amgevita/.
2. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/761024_toc.cfm.
3. https://news.abbvie.com/news/press-releases/abbvie-announces-global-resolution-humira-adalimumab-patent-disputes-with-samsung-bioepis.htm.
4. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/761059Orig1s000TOC.cfm.
5. https://www.boehringer-ingelheim.us/press-release/boehringer-ingelheim-announces-resolution-cyltezo-patent-litigation.
6. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/761058Orig1s000TOC.cfm.
7. https://www.prnewswire.com/news-releases/abbvie-announces-humira-adalimumab-patent-license-with-mylan-300681743.html.
8. https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=761154.
9. https://www.novartis.com/news/media-releases/sandoz-announces-global-resolution-biosimilar-adalimumab-patent-disputes-securing-patient-access.
10. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/761071Orig1s000TOC.cfm.
11. https://www.prnewswire.com/news-releases/abbvie-announces-global-resolution-of-humira-adalimumab-patent-disputes-with-fresenius-kabi-300733366.html.
12. https://www.pfizer.com/news/press-release/press-release-detail/pfizer_reaches_a_global_agreement_with_abbvie.
13. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/761118Orig1s000TOC.cfm.
14. https://investors.coherus.com/news-releases/news-release-details/coherus-biosciences-announces-global-settlement-abbvie-securing.
15. Rosembert D, Malaviya A, How J, et al. P505 Different failure rates after non-medical switching of 744 patients from adalimumab originator to 2 different adalimumab biosimilars at Cambridge University Hospitals, UK: real-world experience. J Crohn’s Colitis. 2020;14(Supplement_1):S438-S439. doi:10.1093/ecco-jcc/jjz203.634
16. https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/125057s415lbl.pdf.
17. https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/761024lbl.pdf.
18. Erskine D, Minshull J. Update on Development of Biosimilar Versions of Adalimumab with Particular Focus on Excipients and Injection Site Reactions.; 2020. https://www.sps.nhs.uk/articles/update-on-development-of-biosimilar-versions-of-adalimumab-with-particular-focus-on-excipients-and-injection-site-reactions/.
19. https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/761058lbl.pdf.
20. https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/761154s000lbl.pdf.
21. https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/761071lbl.pdf.
22. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/761118Orig1s000ChemR.pdf.

About The Author:

Rose Joachim, Ph.D., is a senior healthcare and pharmaceutical analyst at GlobalData. As an analyst, she has authored numerous reports and articles analyzing market dynamics within the autoimmune, allergic, and hematological disease spaces. In 2017, Joachim earned her Ph.D. in biological sciences in public health at Harvard University. Her dissertation research explored the effects of age on immune system function during sepsis. When she wasn’t at the bench, she spent her time teaching and developing new science curricula as part of the Science Education and Academic Leadership certificate program at Harvard. Prior to her graduate studies, Joachim earned her B.S. in biology with a minor in chemistry from The College of New Jersey.