In April and June 2024, Icelandic biosimilar company Alvotech announced promising results from two clinical studies (AVT05-GL-P01, NCT05632211; AVT05-GL-C01, NCT05842213) for AVT05, their candidate golimumab biosimilar. Alvotech is the first company to announce topline results of clinical trials using a proposed biosimilar to Simponi (Janssen Biotech).
Golimumab is a recombinant human IgG1қ monoclonal antibody (mAb) that exhibits multiple glycoforms. It blocks the binding of tumour necrosis factor-alpha (TNF-α) to its receptors, thereby reducing TNF-α-mediated inflammation. Golimumab is approved for the treatment of inflammatory conditions including rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis.
Worldwide revenues in 2023 from sales of Simponi were approximately US$3.2 billion.
PK study – AVT05-GL-P01
Study AVT05-GL-P01, presented at EULAR (European Alliance of Associations for Rheumatology) in June 2024, was a single-dose, randomized, double-blind, 3-arm parallel group study [1, 2]. It assessed the pharmacokinetic (PK) similarity of AVT05 compared to US-licensed and EU-approved reference products (RPs) after subcutaneous injection (50 mg/0.5 mL subcutaneous injection) in 336 healthy participants (male and female aged 18 to 55 years).
Mean serum golimumab concentration-time profiles were comparable across all treatment groups. The 90% confidence intervals (CIs) of the geometric mean ratios (GMRs) for both primary PK endpoints, Cmax and AUC0-inf, were entirely contained within the prespecified margins of 80.00% and 125.00% for each of the 3 pairwise comparisons, supporting the demonstration of PK similarity. This included similarity between both RPs, providing a PK bridge. Secondary PK parameters were also comparable across treatment arms.
Overall, 66.1% of participants experienced at least one treatment-emergent adverse event (TEAE) during the study period. The majority of the TEAEs were mild to moderate in severity. Local administration site reactions were mild in severity and observed in 6.1%, 10.8% and 5.5% of participants in the AVT05, EU-RP, and US-RP arms, respectively. In the same respective treatment groups, 75.7%, 82.9%, and 80.9% participants tested positive for anti-drug antibodies (ADA), of which 57.4%, 61.3%, and 55.5% were furthermore positive for neutralising antibodies (nAb) at least once during the study.
Overall, the study supported a demonstration of PK similarity between AVT05 and the RP with comparable safety, tolerability, and immunogenicity profiles between treatment arms.
Confirmatory study – AVT05-GL-C01
Study AVT05-GL-C01 is a multi-dose, randomized, double-blind, 2-arm multicentre parallel group active control study assessing the comparative efficacy, safety, and immunogenicity, of AVT05 compared to EU RP as combination therapy with MTX in participants with moderate to severe rheumatoid arthritis [3].
The primary outcome measure was the change from baseline to Week 16 in DAS28-CRP, which is a disease activity score measurement for rheumatoid arthritis. At Week 16, the two-sided 90% confidence interval of the least squares mean difference between the two treatment groups was entirely contained within the prespecified equivalence margin, supporting a demonstration of comparative efficacy. The safety and immunogenicity profile of AVT05 was also similar to that observed for the reference product over the same time period. Additionally, no clinically meaningful differences in safety were observed through Week 24. Study AVT05-GL-C01 continues during 2024.
Brief overview of Alvotech’s biosimilar approvals and in clinical trials
Alvotech’s current portfolio of 11 biosimilar products and product candidates includes:
1. One launched product (adalimumab biosimilar AVT02): Hukyndra and Libmyris – approved in Europe in 2021 [4]; Simlandi (adalimumab-ryvk) – approved in the US in February 2024 with interchangeable status [5]; also approved in many other countries including Australia, Bolivia, Canada, Egypt, Israel, Morocco, Saudi Arabia, South Africa, and Peru
2. One approved biosimilar (ustekinumab biosimilar AVT04): Uzpruvo – approved in Europe in January 2024 [6]; Selarsdi (ustekinumab-aekn) – approved in the US in April 2024 [7], also approved in Canada and Japan
3. Six candidate biosimilars: AVT03 (denosumab), AVT05 (golimumab), AVT06 (aflibercept), AVT16 (vedolizumab), AVT23 (omalizumab), and AVT33 (pembrolizumab) – along with several undisclosed biosimilar candidates.
References
1. European Alliance of Associations for Rheumatology. EULAR abstract archives [homepage on the Internet]. [cited 2024 Jul 23]. Available from: https://scientific.sparx-ip.net/archiveeular/?c=a&searchfor=golimumab&view=1&item=2024AB0516
2. Alvotech. Alvotech announces positive top-line results from a pharmacokinetic study for AVT05, a proposed biosimilar for Simponi® and Simponi Aria®. Available from: https://investors.alvotech.com/news-releases/news-release-details/alvotech-announces-positive-top-line-results-pharmacokinetic
3. Alvotech. Alvotech announces topline results from a confirmatory clinical study for AVT05, a proposed biosimilar for Simponi® (golimumab). Available from: https://investors.alvotech.com/news-releases/news-release-details/alvotech-announces-topline-results-confirmatory-clinical-study
4. GaBI Online - Generics and Biosimilars Initiative. EMA recommends approval of two adalimumab biosimilars [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2024 Jul 23]. Available from: www.gabionline.net/biosimilars/news/ema-recommends-approval-of-two-adalimumab-biosimilars
5. GaBI Online - Generics and Biosimilars Initiative. FDA approves interchangeable adalimumab bisimilar Simlandi [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2024 Jul 23]. Available from: www.gabionline.net/biosimilars/news/fda-approves-interchangeable-adalimumab-biosimilar-simlandi
6. GaBI Online - Generics and Biosimilars Initiative. EC approval of first ustekinumab biosimilar uzpruvo [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2024 Jul 23]. Available from: www.gabionline.net/biosimilars/news/ec-approval-of-first-ustekinumab-biosimilar-uzpruvo
7. GaBI Online - Generics and Biosimilars Initiative. FDA approves Ustekinumab trastuzumab and tocilizumab biosimilars [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2024 Jul 23]. Available from: www.gabionline.net/biosimilars/news/fda-approves-ustekinumab-trastuzumab-and-tocilizumab-biosimilars
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