The European Medicines Agency (EMA) has accepted Alvotech's Marketing Authorization Application (MAA) for AVT03, a proposed biosimilar to denosumab, marketed as Prolia and Xgeva. This decision marks a significant step toward offering a more affordable alternative for patients in Europe who require treatment for osteoporosis and prevention of bone complications associated with advanced cancer.
AVT03, a human monoclonal antibody, is designed to target and bind with high affinity and specificity to the RANK ligand, a key mediator of osteoclast formation, function, and survival. By preventing the RANK ligand/RANK interaction, AVT03 aims to reduce osteoclast activity, thereby decreasing bone resorption and cancer-induced bone destruction.
Clinical Similarity Demonstrated
Alvotech's MAA is supported by data from several clinical studies. Notably, the AVT03-GL-C01 study, a confirmatory patient study, demonstrated clinical similarity between AVT03 and Prolia in 532 postmenopausal women with osteoporosis. The study met its primary endpoints, showing comparable efficacy, safety, immunogenicity, and pharmacokinetics. Similar primary endpoints were also met in the AVT03-GL-P01 and AVT03-GL-P03 studies, which assessed the pharmacokinetics, safety, and tolerability of AVT03 compared to Prolia and Xgeva, respectively, in healthy adult participants.
Joseph McClellan, Chief Scientific Officer of Alvotech, stated, "EMA acceptance marks an important step towards making AVT03 available to patients and caregivers in Europe. Successful progression in the development of multiple biosimilar candidates demonstrates how Alvotech is able to leverage its end-to-end biosimilars platform in support of broader access to affordable biologic medicines."
Addressing a Significant Unmet Need
Denosumab is a crucial medication for treating osteoporosis and preventing skeletal-related events in cancer patients with bone metastases. Prolia is indicated for osteoporosis in postmenopausal women and men at increased risk of fracture, bone loss in men receiving treatment for prostate cancer, and bone loss in adults at increased risk of fractures treated long-term with corticosteroids. Xgeva is used to prevent bone complications in adults with advanced cancer that has spread to the bone and to treat giant cell tumor of bone in adults and adolescents whose bones have fully developed.
The European denosumab market is currently valued at approximately US$1 billion. However, a significant portion of the population remains untreated. In 2019, an estimated 32 million individuals in Europe had osteoporosis, with 80% being women. Alarmingly, 70% of women eligible for treatment did not receive it, according to the International Osteoporosis Foundation.
Commercialization Strategy
Alvotech has established strategic commercial partnerships with STADA Arzneimittel AG and Dr. Reddy’s Laboratories SA to commercialize AVT03 in Europe, including Switzerland and the UK. These partners will leverage their local expertise to ensure broad access to the biosimilar once approved.
Potential Economic Impact
The introduction of AVT03 as a biosimilar to Prolia and Xgeva has the potential to significantly reduce healthcare costs associated with osteoporosis and cancer-related bone complications. In 2019, the total direct cost of osteoporotic fractures in the European Union, Switzerland, and the UK was estimated at US$63 billion. Biosimilar competition could expand patient access considerably at the same or lower overall costs.
With the EMA's acceptance of the MAA, AVT03 is now under review for potential approval, which, if granted, could transform the treatment landscape for osteoporosis and cancer-induced bone complications in Europe.
