Results of clinical patient trials of Alvotech’s high concentration formulation biosimilar of adalimumab, AVT02, demonstrate comparable efficacy, safety and immunogenicity to the reference product Humira, according to a study published in Biodrugs [1].
AVT02 has been developed by Alvotech and is an approved biosimilar of AbbVie’s Humira (adalimumab) in Europe and Canada [1]. Adalimumab is a recombinant human immunoglobulin 1 (IgG1) monoclonal antibody which was first approved for rheumatoid arthritis in 2002 in the US. This has since been approved in a variety of inflammatory diseases making Humira a blockbuster drug and, following the expiry of the originator patent, a number of biosimilar versions are available worldwide.
A higher concentration, 100 mg/mL, formulation of adalimumab has been available since 2017. This higher concentration dose delivers the same amount of active ingredient (40 mg) in a smaller volume of solution without a citrate buffer. The authors of the current study highlight that this has been shown to have reduced injection site pain [2] and is better tolerated by patients leading to greater adherence [3].
To contribute to the totality of evidence to support AVT02’s use in all indications of the reference product, the researchers based across Europe, carried out a multicentre, double-blind, randomized, parallel group, active control study in patients with moderate to severe chronic plaque psoriasis.
The study was conducted with 413 randomized subjects (with an approximate and randomized 50:50 split between those taking AVT02 and the originator). The primary endpoint was percentage improvement in Psoriasis Area and Severity Index (PASI) score, which at Week 16 was 91.6% for AVT02-treated subjects and 89.6% for the originator Humira.
The researchers note that the secondary efficacy endpoints were all successful in helping to demonstrate bioequivalence. For example, they reflect biosimilarity with the reference product when it comes to the change from baseline in Dermatology Life Quality Index (DLQI) score and number and percentage of subjects achieving static Physician's Global Assessment (sPGA) responses of 'clear' or 'almost clear'.
Overall, the combined endpoints in the study demonstrated that there was similarity to the reference product when it came to the safety, tolerability and immunogenicity profiles of AVT02. The profiles for AVT02 and originator adalimumab were similar at Week 16, and this persisted in the switched and continued groups through to Week 50 of the trial. The authors state that they have therefore demonstrated the similarity of AVT02 when compared to originator reference product, Humira, for chronic plaque psoriasis. There is no clinically meaningful difference between the two products. Based on their findings, the authors state that they anticipate that AVT02 will offer patients both comparable efficacy and improvements in subjective quality of life that originator Humira has provided.
In 2021, the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) announced that it had recommended granting marketing authorization AVT02 adalimumab biosimilar, under the names: Hukyndra and Libmyris [4, 5]. The product has subsequently been launched in several EU countries, as well as Switzerland and Canada. It is also approved in the UK, although it has not yet launched there. The product is approved as Hukyndra and Libmyris in Europe and as Simlandi in Canada [6].
The approval of AVT02 in the US was deferred in September 2021 by the US Food and Drug Administration (FDA), due to travel restrictions during the COVID-19 pandemic. FDA can defer action when no deficiencies have been identified and the application otherwise satisfies the requirements for approval, including safety, efficacy and biosimilarity, but an inspection(s) is necessary yet cannot be completed due to factors including travel restrictions [7]. After FDA completed its inspection of the facility in March 2022, it listed several good manufacturing practices (GMP) deficiencies which withheld approval of the Biologics License Application (BLA) [8]. The company is in the process of addressing the issues to enable the approval of its interchangeable biosimilar in the US. After settlement of patent and trade secret disputes with AbbVie, Alvotech was granted a market launch date in the US of 1 July 2023 [9].
The coordinated launch of AVT02 is being made possible through strategic partnerships with global exclusive commercialization partners, including Teva in the US and STADA in Europe [10], JAMP in Canada [11], as well as Cipla Gulf [12], and other partners in emerging markets.
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References
1. Feldman TF, Reznichenko N, Pulka G, et al. Efficacy, safety and immunogenicity of AVT02 versus originator adalimumab in subjects with moderate to severe chronic plaque psoriasis: a multicentre, double-blind, randomised, parallel group, active control, phase III study. BioDrugs. 2021;35(6):735-48.
2. Nash P, Vanhoof J, Hall S, et al. Randomized crossover comparison of injection site pain with 40 mg/0.4 or 0.8 ml formulations of adalimumab in patients with rheumatoid arthritis. Rheumatol Ther. 2016;3(2):257-70.
3. Bergman M, Patel P, Chen N, et al. Evaluation of adherence and persistence differences between adalimumab citrate-free and citrate formulations for patients with immune-mediated diseases in the United States. Rheumatol Ther. 2021;8(1):109-18.
4. GaBI Online - Generics and Biosimilars Initiative. EMA recommends approval of two adalimumab biosimilars [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2022 Dec 1]. Available from: www.gabionline.net/biosimilars/news/ema-recommends-approval-of-two-adalimumab-biosimilars
5. GaBI Online - Generics and Biosimilars Initiative. Biosimilars approved in Europe [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2022 Dec 1]. Available from: www.gabionline.net/biosimilars/general/biosimilars-approved-in-europe
6. GaBI Online - Generics and Biosimilars Initiative. Canada approves adalimumab biosimilars Simlandi and Yuflyma [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2022 Dec 1]. Available from: www.gabionline.net/biosimilars/news/canada-approves-adalimumab-biosimilars-simlandi-and-yuflyma
7. Alvotech provides update on FDA action regarding AVT02, proposed high-concentration biosimilar to Humira® (adalimumab) [cited 2022 Dec 1]. Available from: https://www.alvotech.com/newsroom/reykjavik-iceland-september-20-2021--alvotech
8. GaBI Online - Generics and Biosimilars Initiative. FDA inspections in Iceland and Singapore for Alvotech and Strides [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2022 Dec 1]. Available from: www.gabionline.net/pharma-news/fda-inspections-in-iceland-and-singapore-for-alvotech-and-strides
9. GaBI Online - Generics and Biosimilars Initiative. AbbVie and Alvotech settle Humira adalimumab disputes [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2022 Dec 1]. Available from: www.gabionline.net/pharma-news/abbvie-and-alvotech-settle-humira-adalimumab-disputes
10. GaBI Online - Generics and Biosimilars Initiative. EMA and FDA accept application for adalimumab biosimilar AVT02 [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2022 Dec 1]. Available from: www.gabionline.net/biosimilars/news/EMA-and-FDA-accept-application-for-adalimumab-biosimilar-AVT02
11. GaBI Online - Generics and Biosimilars Initiative. New adalimumab biosimilars prepare to launch in Canada, US and Europe [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2022 Dec 1]. Available from: www.gabionline.net/biosimilars/news/new-adalimumab-biosimilars-prepare-to-launch-in-canada-us-and-europe
12. GaBI Online - Generics and Biosimilars Initiative. Alvotech and Cipla Gulf partnership announced [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2022 Dec 1]. Available from:
www.gabionline.net/Pharma-News/Alvotech-and-Cipla-Gulf-partnership-announced
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