FDA rejects application of AVT04 ustekinumab biosimilar
The October CRL regarding AVT04 noted that certain deficiencies, which were conveyed following the FDA’s inspection of the company’s Reykjavik facility that concluded in March 2023, must be satisfactorily resolved before the application can be approved. No other deficiencies in the application were noted by the FDA. In response, Alvotech has indicated that it will file a resubmission in due course. 

Ustekinumab is indicated for the treatment of Crohn’s disease, psoriasis and psoriatic arthritis, and the originator is Janssen’s/Johnson & Johnson’s Stelara. It is a humanized monoclonal antibody that interferes with the triggering of the body’s inflammatory response through the suppression of certain cytokines. Specifically, it blocks interleukin IL 12 and IL 23 which help activate certain T cells. It binds to the p 40 subunit of both IL 12 and IL 23 so that they subsequently cannot bind to their receptors [4].  

Alvotech’s AVT04 has been approved in Japan [2] and a marketing authorisation application has been submitted to the European Medicines Agency on 9 February 2023 [3]. 

AVT02 adalimumab biosimilar re-submits interchangeability designation
This is not the first time that such issues with the company’s facility have held back the approval of a biosimilar. In 2022, Alvotech’s high-concentration biosimilar formulation adalimumab formulation, AVT02, was issued a similar CRL [5]. However, Alvotech resubmitted its BLA to the FDA seeking an interchangeability designation for AVT02, in September 2023.  

Adalimumab is a human monoclonal antibody that treats autoimmune diseases by inhibiting tumour necrosis factor (TNF), a soluble inflammatory cytokine. Adalimumab binds to TNF-alpha (TNF-α), preventing it from activating TNF receptors, which cause the inflammatory reactions associated with autoimmune diseases. Adalimumab is indicated for the treatment of rheumatoid, juvenile idiopathic and psoriatic arthritis, ankylosing spondylitis, Crohn’s disease, psoriasis and ulcerative colitis [6].

If approved, AVT02 will compete with a number of other adalimumab biosimilars now approved for the US market.

Related article
Australia and EU: Alvotech Humira and Stada Lucentis biosimilars approved

References
1. GaBI Online - Generics and Biosimilars Initiative. AVT02 biosimilarity with Humira proved in chronic plaque psoriasis treatment [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2023 Oct 31]. Available from: www.gabionline.net/biosimilars/research/avt02-biosimilarity-with-humira-proved-in-chronic-plaque-psoriasis-treatment
2. GaBI Online - Generics and Biosimilars Initiative. Japanese approval for first ustekinumab biosimilar [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2023 Oct 31]. Available from:
www.gabionline.net/biosimilars/news/japanese-approval-for-first-ustekinumab-biosimilar
3. GaBI Online - Generics and Biosimilars Initiative. EMA accepts application for ustekinumab biosimilar AVT04 [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2023 Oct 31]. Available from: www.gabionline.net/biosimilars/news/ema-accepts-application-for-ustekinumab-biosimilar-avt04
4. GaBI Online - Generics and Biosimilars Initiative. Biosimilars of ustekinumab [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2023 Oct 31]. Available from: www.gabionline.net/biosimilars/general/biosimilars-of-ustekinumab
5. 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 2023 Oct 31]. Available from:
www.gabionline.net/pharma-news/fda-inspections-in-iceland-and-singapore-for-alvotech-and-strides
6. GaBI Online - Generics and Biosimilars Initiative. Biosimilars of adalimumab [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2023 Oct 31]. Available from: www.gabionline.net/biosimilars/general/Biosimilars-of-adalimumab

Permission granted to reproduce for personal and non-commercial use only. All other reproduction, copy or reprinting of all or part of any ‘Content’ found on this website is strictly prohibited without the prior consent of the publisher. Contact the publisher to obtain permission before redistributing.

Copyright – Unless otherwise stated all contents of this website are © 2023 Pro Pharma Communications International. All Rights Reserved.