Proposed Denosumab Biosimilar AVT03 Demonstrates Positive Topline Data

Positive topline data of a confirmatory patient study for the proposed denosumab biosimilar AVT03 were announced by Alvotech today.¹ The drug was compared to both denosumab reference product Prolia (denosumab) and Xgeva (denosumab). Results will be used to further support indications of the drug as a proposed biosimilar to Xgeva based on data extrapolation.

“We are pleased with these results, demonstrating clinical similarity between AVT03 and the reference biologic,” stated Joseph McClellan, PhD, Chief Scientific Officer of Alvotech.¹ “These clinical milestones underline the capabilities of our dedicated biosimilar platform and continued diversification of our portfolio.”

The reference products are approved for the treatment of osteoporosis in postmenopausal women and for bone loss in adult men and women who have an increased risk of fracture (Prolia) as well as the prevention of skeletal-related events, including pathological fractures in adult patients with advanced malignancies involving bone (Xgeva). Denosumab is also indicated for the treatment of giant cell tumor in bone.¹

Denosumab targets and binds to the receptor activator of nuclear factor (RANK) ligand membrane protein, which in turn prevents the RANK ligand/RANK interaction from occurring. This results in a reduction of osteoclast numbers and function, thus decreasing bone resorption and cancer-induced bone destruction among these patients.¹

The Trials

The objective of the confirmatory randomized, double-blind, parallel design, repeat dose, multicenter ALVOBOND study was to prove the clinical similarity of AVT03, a human monoclonal antibody, in comparison to Prolia regarding safety, efficacy, immunogenicity, and pharmacokinetics (PK) among a cohort of postmenopausal women with osteoporosis.²

The study enrolled 532 patients, aged 50 years or older, who were clinically diagnosed with osteoporosis. Subjects were randomized to receive either 3 doses of AVT03 or 3 doses of Prolia every 6 months. The trial also included a re-randomization in which patients in the Prolia arm received a third dose of either the biosimilar or reference drug.²

Primary outcome measures included changes from baseline regarding bone mass density (BMD) and a biomarker for bone resorption. Although patients will be followed until the end of the study (18 months), these endpoints were analyzed at both 6 and 12 months after the initial dose. Results showed the study met its primary endpoints.²

In additional randomized, double-blind, parallel-group trials, investigators evaluated the effects of AVT03 compared with Prolia among 209 healthy adult subjects aged between 28 and 55 years, as well as the effects of the biosimilar in comparison to Xgeva among a cohort of 208 healthy adult male participants. Investigators were interested in the safety, tolerability, and pharmacokinetics of the biosimilar. Both trials met their primary endpoints as well.^1,3,4

Although these results are promising, the biosimilarity by regulatory authorities has not been established and AVT03 has not been granted regulatory approval in any country.¹

Alvotech plans to file marketing applications for the biosimilar in major global markets later this year.¹

References

1. ^{Alvotech. Alvotech announces positive topline results from Confirmatory Patient Study for AVT03, a proposed biosimilar for Prolia® and XGEVA®. GlobeNewswire News Room. July 2, 2024. Accessed July 2, 2024. https://www.globenewswire.com/news-release/2024/07/02/2907460/0/en/Alvotech-Announces-Positive-Topline-Results-from-Confirmatory-Patient-Study-for-AVT03-a-Proposed-Biosimilar-for-Prolia-and-Xgeva.html.}
2. ^{Multicenter Study in Postmenopausal Women With Osteoporosis, ALVOBOND (ALVOBOND). Clinicaltrials.gov. May 28, 2024. Accessed July 2, 2024. https://clinicaltrials.gov/study/NCT05395091.}
3. ^{AVT03 With Prolia in Healthy Male Subjects. Clinicaltrials.gov. May 29, 2024. Accessed July 2, 2024. https://clinicaltrials.gov/study/NCT05126784.}
4. ^{AVT03 With Xgeva in Healthy Male Subjects. Clinicaltrials.gov. May 29, 2024. Accessed July 2, 2024. https://clinicaltrials.gov/study/NCT05876949.}