Alvotech’s AVT05 in phase III rheumatoid arthritis study, as the sole candidate

The patent for Janssen’s second-generation, tumour necrosis factor-alpha (TNF)-a inhibitor Simponi (golimumab), is scheduled to expire in 2024 and in 2025 in the US and EU, respectively. It was first approved throughout the major markets such as the US, 5EU (France, Germany, Italy, Spain, the UK), Japan, Canada, and Australia between 2009 and 2011 to address various autoimmune disorders, including rheumatoid arthritis (RA). As per a report by GlobalData entitled Rheumatoid Arthritis: Global Drug Forecast and Market Analysis to 2029, in the 8MM, (US, 5EU, Japan, and Australia) the number of individuals affected by RA is projected to rise from 6,308,268 cases in 2019 to 6,980,823 cases by 2029, with an annual growth rate (AGR) of 1.07% during the forecast period.

There are several anti-TNF therapies on the market for the treatment of RA, such as AbbVie’s anti-TNF Humira (adalimumab), UCB’s anti-TNF Cimzia (certolizumab pegol), Pfizer’s Enbrel (etanercept), and Janssen’s Remicade (infliximab). Another important therapy within this drug class for the treatment of RA is Janssen’s Simponi (golimumab), which is a human monoclonal antibody that specifically targets and neutralizes an excess of TNF, a protein responsible for inflammation and potential harm to bones, cartilage, and tissues when produced excessively. Golimumab binds to both the soluble and trans membrane forms of human (TNF)-a which consequently inhibits the biological activity of (TNF)-a. Simponi, when used alongside methotrexate, is approved for treating adults who have moderately to severely active RA.

As patent expiration approaches for many of these therapies, strategic activity within this space indicates that the landscape is shifting; in May 2023, Alvotech and Advanz Pharma announced an extended strategic partnership with plans to supply and commercialise five proposed biosimilars in Europe, including Simponi, Entyvio, and three other undisclosed candidates, that are all estimated to be worth upwards of $4bn (Alvotech, press release, 24 May 2023). Consequently, in May 2023, Alvotech’s AVT05 entered a Phase III RA study (NCT05842213), wherein the purpose is to investigate the efficacy, safety, and immunogenicity of subcutaneous AVT05 against Simponi, in combination with methotrexate (MTX) amongst subjects with moderate to severe RA. Although biosimilarity has not been established yet, the fact that AVT05 has progressed to Phase III alludes to a promising pipeline agent, which will be beneficial for Alvotech as since its inception, the company has incurred net losses each year and accumulated a deficit of $1,140.5 million as of December 31, 2021. However, Alvotech has been expanding its portfolio; currently it has 11 biosimilar candidates in its pipeline for various diseases of which five of them, AVT02, AVT03, AVT04, AVT05, and AVT16b, fall under the therapy area of Immunology.

The company’s most advanced product is AVT02, a high-concentration biosimilar to Humira (adalimumab) and collectively, the product revenue for the first six months of 2023 increased to $22.7m, as opposed to $3.9m for the same period in 2022 (Alvotech, press release, 30 August 2023). The approval and launch of AVT05 will potentially continue this upwards trend.

Besides Alovtech, Reliance Life Sciences is also engaged in the development of a Simponi biosimilar, R-TPR-044, (CTRI/2020/09/027958), which also investigates the efficacy, safety, and immunogenicity of R-TPR-044 against Simponi in patients with moderately to severely active RA. As per GlobalData’s pipeline drug database, R-TPR-044 is currently in Phase III. However, it is worth noting that this clinical trial is specific to India, as opposed to Alvotech’s clinical trial which is being conducted in Europe. AVT05’s wider clinical trial geographic coverage puts Alvotech in a strong position as the sole candidate for global development of a Simponi biosimilar for RA and potentially enables the company towards monopolizing heavily on Simponi’s patent expiry.

According to GlobalData, companies that have a substantial portfolio of both marketed drugs and pipeline agents for RA such as AbbVie, Pfizer, Amgen, and Roche/Genentech will not be majorly affected by this biosimilar erosion; however, overall sales will stymie and therefore adopting a solid corporate strategy is key. GlobalData highlights that one of the key trends in corporate strategy is to develop new innovative agents in the treatment landscape at hand to prevent the financial impact of biosimilar erosion. Going by that general approach, Johnson & Johnson’s nipocalimab (M-281) is under clinical development in Phase II for RA (NCT06028438) for which GlobalData predicts a 36% phase transition success rate (PTSR) into Phase III. When and if the pipeline agent is approved by the FDA for RA, this development can potentially counteract the market share loss of Simponi and bolster the company’s presence in the RA space.