Positive topline results announced from confirmatory patient study for AVT 03, a proposed biosimilar for Prolia (denosumab) and Xgeva (denosumab)

The objective of the study is to demonstrate clinical similarity of AVT 03 to Prolia in terms of efficacy, safety, immunogenicity, and pharmacokinetics (PK) in postmenopausal women with osteoporosis. The results will be used to support additional indications for AVT 03 as a proposed biosimilar to Xgeva, based on extrapolation.

“We are pleased with these results, demonstrating clinical similarity between AVT03 and the reference biologic. In addition, we have now obtained positive topline results from two PK studies, that show equivalent PK, safety, and tolerability of AVT 03 compared to Prolia and Xgeva, respectively. These clinical milestones underline the capabilities of our dedicated biosimilar platform and continued diversification of our portfolio. We expect to file marketing applications for AVT 03 for major global markets later this year,” said Joseph McClellan, Chief Scientific Officer of Alvotech.

Prolia (denosumab) is indicated for the treatment of osteoporosis in postmenopausal women and for bone loss in adult men and women at increased risk of fracture. Xgeva (denosumab), which is the same biologic in a different presentation, is indicated for prevention of skeletal-related events such as pathological fractures in adults with advanced malignancies involving bone. It is also indicated for the treatment of giant cell tumor in bone.

The confirmatory patient study, AVT03-GL-C01, is a randomized, double-blind, parallel design, repeat dose, two arm, multicenter study comparing the efficacy, safety, immunogenicity, and pharmacokinetic profiles of AVT 03 and Prolia in postmenopausal women with osteoporosis. Approximately 532 participants, postmenopausal women 50 years or older diagnosed with osteoporosis, were randomly assigned between the two arms. Each participant receives three doses of either AVT 03 or Prolia, at six-month intervals. The study included a re-randomization in the Prolia arm, with participants receiving a third dose of either AVT 03 or Prolia. The primary outcome measures were change from baseline in bone mass density (BMD) and a biomarker for bone resorption. The primary endpoints were measured at 6 and 12 months, but all participants will be followed until an end of study visit after 18 months from the initial dose.

The AVT03-GL-P01 study, assessed the PK, safety, and tolerability of AVT 03 compared to Prolia in 209 healthy adult participants, and the AVT03-GL-P03 study assessed the PK, safety, and tolerability of AVT 03 compared to Xgeva in 208 healthy adult participants. Both studies met their primary endpoints.