CONEXXENCE (denosumab-bnht)

Drug overview for CONEXXENCE (denosumab-bnht):

Generic name: DENOSUMAB-BNHT (den-OH-sue-mab)
Drug class: Hypercalcemia Agents
Therapeutic class: Endocrine

Denosumab, denosumab-bbdz, denosumab-bmwo, denosumab-bnht, denosumab-desu, denosumab-dssb, denosumab-kyqq, denosumab-mobz, denosumab-nxxp, and denosumab-qbde, fully human monoclonal antibodies that are specific for the receptor activator of nuclear factor kappa-B ligand (RANKL) and act as RANKL inhibitors, are bone resorption inhibitors. FDA defines a biosimilar as a biological product that is highly similar to an FDA-licensed reference biological with the exception of minor differences in clinically inactive components and for which there are no clinically meaningful differences in safety, purity, or potency. The claim of biosimilarity is based on a totality-of-evidence approach, which includes consideration of data from analytical, animal, and clinical studies (e.g., human pharmacokinetic and pharmacodynamic studies, clinical immunogenicity assessment, additional comparative clinical studies).

Therefore, biosimilarity may be established even when there are formulation or minor structural differences as long as these differences are not clinically meaningful. Biosimilars are approved through an abbreviated licensure pathway that establishes biosimilarity between the proposed biological and the reference biological but does not independently establish safety and effectiveness of the proposed biological. In order to be considered an interchangeable biosimilar, a biological product must meet additional requirements beyond demonstrating biosimilarity to its reference product; these requirements include demonstrating that the biological product can be expected to produce the same clinical results as the reference product in any given patient and, for a biological product that is administered more than once to an individual, the risk in terms of safety or diminished efficacy of alternating or switching between use of the biological product and the reference product is no greater than the risk of using the reference product without such alteration or switch.

Biosimilar products that are interchangeable can be substituted for the reference product without the intervention of the healthcare provider who prescribed the reference product. All of the approved denosumab biosimilars have brand name products that are designated as interchangeable with denosumab (Prolia(R)) or denosumab (Xgeva(R)). In this monograph, unless otherwise stated, the term ''denosumab products'' refers to denosumab (the reference drug) and its approved biosimilars.

Denosumab (Prolia(R)) is used in the treatment of osteoporosis in postmenopausal women and men at high risk for fracture, in the treatment of glucocorticoid-induced osteoporosis in patients at high risk for fracture, and to increase bone mass in patients at high risk for fracture who are receiving androgen deprivation or aromatase inhibitor therapy. Denosumab (Xgeva(R)) is used to prevent skeletal-related events (SREs) in patients with multiple myeloma or with bone metastases from solid tumors. Denosumab (Xgeva(R)) also is used for the treatment of giant cell tumor of bone and for the treatment of bisphosphonate-refractory hypercalcemia associated with malignant neoplasms; denosumab has been designated an orphan drug by FDA for these uses.

Several denosumab biosimilars are available. Biosimilarity of these products has been demonstrated for the indications described in Table 1. Biosimilarity to originator denosumab is additionally supported by comparative clinical studies in postmenopausal women with osteoporosis (denosumab-bbdz and denosumab-bmwo).

Table 1. Denosumab Biosimilar Products and FDA Licensed Indications. FDA OP in OP in GCI OP Bone Bone MM GCTB HCM Indicat PM Men Loss in Loss in ion Women PC BC Denosum X X X X X ab-bbdz (Jubbon ti(R)) Denosum X X X ab-bbdz (Wyost( R)) Denosum X X X X X ab-bmwo (Stoboc lo(R)) Denosum X X X ab-bmwo (Osenve lt(R)) Denosum X X X X X ab-bnht (Conexx ence(R) ) Denosum X X X ab-bnht (Bomynt ra(R)) Denosum X X X ab-desu (Jubere q(R)) Denosum X X X X X ab-desu (Osvyrt i(R)) Denosum X X X X X ab-dssb (Ospomy v(R)) Denosum X X X ab-dssb (Xbryk( R)) Denosum X X X ab-kyqq (Aukels o(R)) Denosum X X X X X ab-kyqq (Bosaya (R)) Denosum X X X X X ab-mobz (Boncre sa(R)) Denosum X X X ab-mobz (Oziltu s(R)) Denosum X X X X X ab-nxxp (Bildyo s(R)) Denosum X X X ab-nxxp (Bilpre vda(R)) Denosum X X X X X ab-qbde (Enoby( R)) Denosum X X X ab-qbde (Xtrenb o(R)) BC, breast cancer; GCI, glucocorticoid-induced; GCTB, giant cell tumor of bone; HCM, hypercalcemia of malignancy; MM, multiple myeloma; OP, osteoporosis; PC, prostate cancer; PM, postmenopausal.