Introduction
Jubbonti (denosumab-bbdz) is a biosimilar to Prolia (denosumab) approved by the FDA in April 2024. It is a RANK ligand (RANKL) inhibitor indicated for the treatment of osteoporosis in postmenopausal women at high risk for fracture and to increase bone mass in men at high risk for fracture. Jubbonti represents the first biosimilar approved for denosumab, offering a potentially more accessible treatment option for patients requiring bone-modifying therapy.
Mechanism of Action
Jubbonti binds to RANKL, a transmembrane or soluble protein essential for the formation, function, and survival of osteoclasts. By inhibiting RANKL, Jubbonti prevents osteoclast formation, function, and survival, thereby reducing bone resorption and increasing bone mass and strength. This mechanism is identical to that of the reference product, denosumab.
Indications
Jubbonti is FDA-approved for:
- Treatment of osteoporosis in postmenopausal women at high risk for fracture
- Treatment to increase bone mass in men at high risk for fracture
These indications are identical to those of the reference product, Prolia (denosumab).
Dosage and Administration
Standard dosing: 60 mg administered subcutaneously once every 6 months Administration:- Administer by subcutaneous injection in the upper arm, upper thigh, or abdomen
- Ensure adequate calcium and vitamin D supplementation
- Do not administer intravenously
- Renal impairment: No dosage adjustment necessary
- Hepatic impairment: No dosage adjustment necessary
- Elderly patients: No dosage adjustment necessary
Pharmacokinetics
Absorption: Bioavailability is approximately 62% following subcutaneous administration Distribution: Volume of distribution is approximately 3.1 L Metabolism: Degraded via proteolytic pathways throughout the body; not metabolized by cytochrome P450 enzymes Elimination: Clearance occurs via phagocytosis by the reticuloendothelial system; terminal half-life is approximately 25.4 daysContraindications
- Hypersensitivity to denosumab or any component of the formulation
- Hypocalcemia (must be corrected prior to initiation)
- Pregnancy (based on animal data showing fetal harm)
Warnings and Precautions
Hypocalcemia: May occur, especially in patients with severe renal impairment. Correct hypocalcemia before initiation and ensure adequate calcium and vitamin D intake. Osteonecrosis of the jaw: Has been reported, primarily in cancer patients receiving higher doses Atypical femoral fractures: Have been reported with long-term use Serious infections: Increased risk of serious infections may occur Skin reactions: Dermatologic adverse reactions including dermatitis, eczema, and rash may occur Multiple vertebral fractures: Following discontinuation of treatment have been reportedDrug Interactions
- Corticosteroids: May increase risk of serious infections
- Immunosuppressants: May increase risk of serious infections
- Other bone-modifying agents: Concurrent use not recommended
- Calcium-lowering medications: May increase risk of hypocalcemia
Adverse Effects
Common adverse reactions (≥5%):- Back pain (34.7%)
- Pain in extremity (11.7%)
- Musculoskeletal pain (7.6%)
- Hypercholesterolemia (7.2%)
- Cystitis (5.9%)
- Hypocalcemia
- Serious infections
- Dermatologic reactions
- Osteonecrosis of the jaw
- Atypical femoral fractures
Monitoring Parameters
- Serum calcium levels prior to each dose and within 2 weeks after initiation
- Bone mineral density (BMD) every 1-2 years
- Renal function
- Signs and symptoms of hypocalcemia
- Dental examinations prior to initiation and during treatment
- Signs of infection
- Skin reactions
Patient Education
- Importance of adherence to the every-6-month dosing schedule
- Need for adequate calcium (at least 1200 mg daily) and vitamin D (800-1000 IU daily) supplementation
- Signs and symptoms of hypocalcemia to report (muscle spasms, twitching, numbness, tingling)
- Importance of good dental hygiene and regular dental check-ups
- Need to report any thigh or groin pain
- Importance of informing all healthcare providers about Jubbonti treatment
- Not to discontinue treatment without consulting their healthcare provider
References
1. FDA Approval Letter: Jubbonti (denosumab-bbdz). April 2024 2. FDA Biosimilar Product Information. Jubbonti prescribing information 3. Cummings SR, et al. Denosumab for prevention of fractures in postmenopausal women with osteoporosis. N Engl J Med. 2009;361(8):756-765 4. Bone HG, et al. 10 years of denosumab treatment in postmenopausal women with osteoporosis: results from the phase 3 randomised FREEDOM trial and open-label extension. Lancet Diabetes Endocrinol. 2017;5(7):513-523 5. Watts NB, et al. Denosumab treatment in men with osteoporosis: a randomized, multicenter, double-blind, placebo-controlled trial. J Clin Endocrinol Metab. 2012;97(9):3162-3170 6. Söreskog E, et al. Risk of osteonecrosis of the jaw in denosumab treated patients: a systematic review and meta-analysis. J Bone Miner Res. 2021;36(7):1242-1249
Note: This monograph is based on the most current available information as of April 2024. Always consult the most recent prescribing information and clinical guidelines before making treatment decisions.