Assessing Humira® (adalimumab) Biosimilars

---

The Buzz Around Biosimilars

A biosimilar drug, as defined by the US Food and Drug Administration (FDA), is a biopharmaceutical that is highly similar to an already licensed biologic product, known as the reference product. Despite minor differences in clinically inactive components, there are no clinically meaningful differences in terms of purity, potency, and safety between a biosimilar and its reference product. The development of biosimilars is a challenging, multistep process that involves comprehensive structural and functional characterization throughout the biosimilar's development. This process often includes in vivo nonclinical evaluations and comparative clinical pharmacology studies, all conducted in direct comparison to the reference product. The development of biosimilars is inherently complex due to the nature of biological medicines. Unlike generic drugs, which are chemically synthesized and identical to their reference products, biosimilars are produced using living organisms. This makes it impossible to create an identical copy of a biological medicine. Consequently, biosimilars can only be similar to the reference product, acknowledging that specific differences may exist due to variations in manufacturing processes. These differences may include variations in the three-dimensional structure, the amount of acid-base variants, and the glycosylation profile, which are considered minor but can potentially affect the efficacy and safety of the end-product.^1,2

The landscape of biopharmaceuticals has been evolving rapidly, leading to an increase in the development and approval of biosimilars. Several factors contribute to this trend. One significant factor is the expiry of patents for many original biotechnological products. As these patents expire, opportunities arise for the development of biosimilars. These biosimilar medicines are designed to be similar to the original biologics but cannot be identical due to the unique manufacturing processes involved. Regulatory support has also played a crucial role in the rise of biosimilars. Regulatory frameworks around the world have become increasingly supportive of biosimilars, recognizing their potential to offer similar therapeutic benefits at a lower cost. ^1,2

While the criteria for demonstrating similarity can vary globally, regulatory authorities universally require robust scientific evidence to ensure that any differences between biosimilars and reference products are not clinically meaningful. This rigorous approval process helps maintain high standards of quality, safety, and efficacy for biosimilars. Cost efficiency is another driving factor behind the growing presence of biosimilars. Biologics are often expensive, and biosimilars offer a cost-effective alternative, making treatments more accessible to patients and reducing healthcare costs. The introduction of biosimilars into the market increases competition, which can lead to lower prices and greater availability of biologic therapies. Technological advancements in biotechnology and analytical techniques have also contributed to the rise of biosimilars. These advancements have enhanced the ability to develop biosimilars that are highly similar to their reference products. Improved technologies allow for more precise characterization and comparison, ensuring that biosimilars meet stringent regulatory requirements. ^1,2

Despite challenges in their development, biosimilars are becoming more prevalent in the healthcare market. Humira® (adalimumab) serves as a prime example of this trend. Adalimumab, an injectable medication used to treat several autoimmune conditions, has been available as a brand-name medication in the U.S. since 2002. Since 2016, a total of 10 adalimumab biosimilars have been approved in the U.S (see Table 1). ^3-13

Notably, guidelines do not differentiate between the reference adalimumab product and its biosimilars, and there is a general lack of direct comparative data. Additionally, differences exist between these agents in terms of indications, dosage form strength, latex content, and excipients. Originally, adalimumab formulations had lower concentrations and contained citrate, which can increase injection discomfort. Most biosimilars are based on this formula but without citrate. Newer Humira products are citrate-free and have higher concentrations, potentially making injections easier and faster. Some biosimilars also offer high-concentration forms either approved or under FDA review. ^3-13

As biosimilars, such as adalimumab, become increasingly prevalent, immunogenicity emerges as a significant concern within the realm of biotherapeutics. Biosimilars have the potential to trigger immune responses akin to their reference products or original biologics, thereby impacting their effectiveness and safety. Immunogenicity manifests through the production of anti-drug antibodies (ADAs) post-treatment, leading to hypersensitivity reactions and diminished drug efficacy. Neutralizing antibodies, binding to the active site of the biologic or biosimilar, can impair their function, while non-neutralizing antibodies may still influence drug availability and therapeutic effectiveness. Therefore, careful monitoring of immunogenicity is essential to ensure the safety and efficacy of biosimilar therapies.²

Overall, biosimilars play a crucial role in increasing access to high-quality, affordable treatments for patients while promoting sustainability and innovation in healthcare systems. The approval of adalimumab biosimilars specifically marks a significant milestone in the landscape of biologic therapies. These biosimilars offer a promising avenue for increasing patient access to essential treatments, potentially improving patient outcomes in the realm of autoimmune diseases.

1. Iskit AB. Key concepts in biosimilar medicines: What physicians must know. North Clin Istanb. 2022;9(1):86-91. Published 2022 Feb 10. doi:10.14744/nci.2021.84669
2. Padda IS, Bhatt R, Rehman O, Parmar M. Biosimilars Use in Medicine for Inflammatory Diseases. In: StatPearls. Treasure Island (FL): StatPearls Publishing; August 28, 2023.
3. Humira® (adalimumab, subcutaneous, injection, solution, kit). Prescribing information. AbbVie; 2024.
4. Cyltezo® (adalimumab-adbm, subcutaneous, injection, solution). Prescribing information. Boehringer Ingelheim; 2023.
5. Abrilada® (adalimumab-afzb, subcutaneous, injection, solution). Prescribing information. Pfizer; 2024.
6. Simlandi (adalimumab-ryvk, subcutaneous, injection, solution). Prescribing information. Alvotech; 2024.
7. Amjevita™ (adalimumab-atto, subcutaneous, injection, solution). Prescribing information. Amgen; 2023.
8. Hyrimoz® (adalimumab-adaz, subcutaneous, injection, solution). Prescribing information. Sandoz; 2023.
9. Hadlima™ (adalimumab-bwwd, subcutaneous, injection, solution). Prescribing information. Organon; 2023.
10. Hulio® (adalimumab-fkjp, subcutaneous, injection, solution). Prescribing information. Biocon; 2023.
11. Yusimry™ (adalimumab-aqvh, subcutaneous, injection, solution). Prescribing information. Coherus; 2023.
12. Idacio® (adalimumab-aacf, subcutaneous, injection, solution). Prescribing information. Fresenius Kabi; 2023.
13. Yuflyma® (adalimumab-aaty, subcutaneous, injection, solution). Prescribing information. Celltrion; 2024. 

Share

Related Posts