Current biologic osteoporosis treatments may be expensive, and PROLIA (denosumab) is one of the more expensive medications covered by Medicare.13,14 As of 2025, BILDYOS is ~55% less expensive than PROLIA.* Referenced prices are derived from published price lists and do not necessarily reflect actual prices paid by consumers or dispensers. Lower acquisition costs alone do not necessarily reflect a cost advantage in the outcome of the condition treated because there are other variables that affect relative costs.
*Based on comparison of wholesale acquisition cost (WAC) per injection. WAC prices: BILDYOS $844.00 per injection; PROLIA $1,875.43 per injection (Source: Medi-Span® Price Rx® as of Sept 2025).
PD, pharmacodynamic; PK, pharmacokinetic.
A 2-part pharmacokinetic similarity study of BILDYOS (HLX14) and reference denosumab demonstrated biosimilarity in PK, PD, safety, and immunogenicity endpoints.
Between June 17, 2022, and June 5, 2024, the study enrolled 514 postmenopausal women between the ages of 60 and 90 with osteoporosis at high risk for fracture. All had BMD T-scores between -2.5 and -4.0 at the lumbar spine or total hip. Eligible patients were randomized 1:1 to receive 60 mg BILDYOS (HLX14) or 60 mg EU-denosumab (PROLIA) every 6 months. At Week 52, prior to dose 3, the PROLIA group was re-randomized 1:1 to stay on their initial therapy or switch to BILDYOS, while 220 patients already on BILDYOS continued with a third dose of BILDYOS.15,†
†Participants were required to take at least 1,000 mg of calcium and at least 400 IU of vitamin D daily.15
‡74 participants from treatment period 1 did not continue to receive treatment in treatment period 2.15
BMD, bone mineral density; EU, European Union; IU, international unit; SC, subcutaneous.
Percent change in BMD at the lumbar spine from baseline to Week 52 (Day 365) as assessed by central imaging.
Area under the effect-time curve for percent change of s-CTX from baseline to Week 26 (AUEC0–26W) (Day 183).
Percent changes in BMD at the lumbar spine from baseline to Weeks 26, 52, and 78 (assessed by Investigator); fracture rate from baseline to Weeks 52 and 78; percent changes in BMD at the lumbar spine from baseline to Weeks 26 and 78 (assessed by the central imaging); percent changes in BMD at total hip from baseline to Weeks 26, 52, and 78 (assessed by the central imaging and Investigator); percent changes in BMD at the femoral neck from baseline to Weeks 26, 52, and 78 (assessed by the central imaging and Investigator); relative percent changes in s-CTX from baseline to D15, D29, D57, D92, D106, D134, D162, D183 (within 7 days prior to the second dose), D274, D365 (within 7 days prior to the third dose), and D547 (at the end-of-study visit); relative percent changes in serum procollagen type 1 N propeptide (s-P1NP) from baseline to D15, D29, D57, D92, D106, D134, D162, D183 (within 7 days prior to the second dose), D274, D365 (within 7 days prior to the third dose), and D547 (at the end-of-study visit).
Postmenopausal women with osteoporosis aged 60–90 years with BMD T-scores between -2.5 and -4.0 at the lumbar spine or total hip as assessed by central imaging at the time of screening, at least 2 vertebrae in the L1–L4 region of lumbar spine, and at least 1 hip evaluable by DXA.
D, day; DXA, dual-energy X-ray absorptiometry; s-CTX, serum C-terminal telopeptide of type 1 collagen.
This is not the full list of exclusion criteria.
From baseline to Week 52, both the BILDYOS and the PROLIA groups increased lumbar spine BMD. The adjusted mean difference between the 2 groups was 0.23% (P=0.518).15
The 90% CI and 95% CI for the difference both fell within the prespecified equivalence margins of −1.45% to 1.45%.15
§Based on the ITT set, with the application of hypothesis strategy for handling intercurrent events, the mean (SD) percent changes from baseline to Week 52 in BMD at the lumbar spine assessed by the central imaging for subjects in the HLX14 and PROLIA groups were 6.10% (3.951%) and 5.90% (3.834%), respectively.
||Adjusted for baseline BMD values and BMI stratification factor (<25, 25-30, >30) using the ANCOVA model.15
ANCOVA, analysis of covariance; BMI, body mass index; CI, confidence interval; ITT, intention-to-treat; SD, standard deviation.
The primary PD endpoint analysis results of AUEC0-26W for percent change from baseline of s-CTX of BILDYOS (HLX14) and PROLIA were equivalent between BILDYOS and PROLIA.15
The geometric LS mean ratio of AUEC0-26W (primary PD endpoint) for participants in the BILDYOS group vs PROLIA group was 1.01 (90% CI: 0.99, 1.04; 95% CI: 0.98, 1.05), and the 90% CI and 95% CI for the geometric LS mean ratio of AUEC0-26W both fell within the prespecified equivalence margins (0.8, 1.25), demonstrating the PD equivalence between BILDYOS and PROLIA. The supplementary analysis results were consistent with the primary PD results, further supporting the PD equivalence between BILDYOS and PROLIA.15
After administration of BILDYOS and PROLIA, the serum denosumab concentration profiles were broadly superimposable.
Serum denosumab concentrations at each timepoint were similar between groups across the different treatment periods (BILDYOS and PROLIA groups in treatment period 1 [from baseline to Week 52]; BILDYOS/BILDYOS, PROLIA/BILDYOS, and PROLIA/PROLIA groups in treatment period 2 [from Week 52 to Week 78]). A single transition treatment from PROLIA to BILDYOS did not impact the PK evaluation results.15
For treatment period 1 and treatment period 2, serum concentrations of BILDYOS and PROLIA were summarized at nominal sample time according to treatment group by the number of below the limit of quantification (BLQ); number of observations; maximum, median, minimum, and standard deviation; arithmetic mean; geometric mean (geomean); CV; and geometric CV (CVb%).15
CV, coefficient of variation; CVb, coefficient of variation between batches; LS, least squares.
↑: Receiving the study treatment.
n for D0–365: Number of subjects in the pharmacokinetic set.
n for D365–547: Number of subjects in the pharmacokinetic set and receiving the third dose.
Based on the safety set, 452 (87.9%) participants experienced treatment emergent adverse events (TEAEs), including 222 (86.7%) participants in the HLX14 group and 230 (89.1%) in the PROLIA group.15
N: The number of subjects in the analysis set.
n: The number of subjects in specific category; %: (n/N*100).
TEAE (Week 0 to Week 52) was defined as an AE that first occurred or worsened in severity between the first dose administration and the third dose administration (exclusive) for subjects who entered treatment period 2, or to the end for those who did not enter treatment period 2.15
Based on the extension safety set, 316 (71.8%) subjects experienced TEAEs, including 153 (69.5%) subjects in the HLX14/HLX14 group, 84 (76.4%) subjects in the PROLIA/HLX14 group and 79 (71.8%) subjects in the PROLIA/PROLIA group.15
N: The number of subjects in the analysis set.
n: The number of subjects in specific category; %: (n/N*100).
TEAE for treatment period 2 (“from Week 52 to Week 78”) was defined as an AE that first occurred or worsened in severity in the period from the third dose administrated date to the end for the subjects who entered the treatment period 2.15
¶Treatment periods 1 and 2 are combined from baseline to Week 78.
HLX14 use only means subject used HLX14 in treatment period 1 and discontinued or continued to use HLX14 in treatment period 2.15
PROLIA use only means subject who used PROLIA in treatment period 1 and discontinued or continued to use PROLIA in treatment period 2.15
Overall positive rate for ADA/NAb was calculated as the number of subjects who have received at least 1 dose of the study drug with positive results/the total number of subjects with at least 1 ADA testing result post-dose administration.15
BILDYOS is indicated for the treatment of postmenopausal women with osteoporosis at high risk for fracture, defined as a history of osteoporotic fracture, or multiple risk factors for fracture; or patients who have failed or are intolerant to other available osteoporosis therapy. In postmenopausal women with osteoporosis, BILDYOS reduces the incidence of vertebral, nonvertebral, and hip fractures.
BILDYOS is indicated for treatment to increase bone mass in men with osteoporosis at high risk for fracture, defined as a history of osteoporotic fracture, or multiple risk factors for fracture; or patients who have failed or are intolerant to other available osteoporosis therapy.
BILDYOS is indicated for the treatment of glucocorticoid-induced osteoporosis in men and women at high risk of fracture who are either initiating or continuing systemic glucocorticoids in a daily dosage equivalent to 7.5 mg or greater of prednisone and expected to remain on glucocorticoids for at least 6 months. High risk of fracture is defined as a history of osteoporotic fracture, multiple risk factors for fracture, or patients who have failed or are intolerant to other available osteoporosis therapy.
BILDYOS is indicated as a treatment to increase bone mass in men at high risk for fracture receiving androgen deprivation therapy (ADT) for nonmetastatic prostate cancer. In these patients, denosumab products also reduced the incidence of vertebral fractures.
BILDYOS is indicated as a treatment to increase bone mass in women at high risk for fracture receiving adjuvant aromatase inhibitor therapy for breast cancer.
Patients with advanced chronic kidney disease (eGFR <30mL/min/1.73m2), including dialysis dependent patients, are at greater risk of severe hypocalcemia following denosumab products administration. Severe hypocalcemia resulting in hospitalization, life-threatening events, and fatal cases have been reported.
The presence of chronic kidney disease-mineral bone disorder (CKD-MBD) markedly increases the risk of hypocalcemia in these patients.
Prior to initiating BILDYOS in patients with advanced chronic kidney disease, evaluate for the presence of CKD-MBD. Treatment with BILDYOS in these patients should be supervised by a health care provider with expertise in the diagnosis and management of CKD-MBD.
BILDYOS is contraindicated in patients with hypocalcemia. Pre-existing hypocalcemia must be corrected prior to initiating BILDYOS. BILDYOS is contraindicated in women who are pregnant and may cause fetal harm when administered to a pregnant woman. In women of reproductive potential, pregnancy testing should be performed prior to initiating treatment with BILDYOS. BILDYOS is contraindicated in patients with a history of systemic hypersensitivity to any component of the product. Reactions have included anaphylaxis, facial swelling, and urticaria.
Denosumab products can cause severe hypocalcemia and fatal cases have been reported. Pre-existing hypocalcemia must be corrected prior to initiating therapy with BILDYOS. Adequately supplement all patients with calcium and vitamin D.
In patients without advanced chronic kidney disease who are predisposed to hypocalcemia and disturbances of mineral metabolism (eg, treatment with other calcium lowering drugs), assess serum calcium and mineral levels (phosphorus and magnesium) 10 to 14 days after BILDYOS injection.
The active ingredient in BILDYOS is denosumab. Patients receiving BILDYOS should not receive other denosumab products concomitantly.
Clinically significant hypersensitivity, including anaphylaxis, has been reported with denosumab products. Symptoms have included hypotension, dyspnea, throat tightness, facial and upper airway edema, pruritus, and urticaria. If an anaphylactic or other clinically significant allergic reaction occurs, initiate appropriate therapy and discontinue further use of BILDYOS.
ONJ, which can occur spontaneously, is generally associated with tooth extraction and/or local infection with delayed healing. ONJ has been reported in patients receiving denosumab products. A routine oral exam should be performed by the prescriber prior to initiation of BILDYOS. A dental examination with appropriate preventive dentistry is recommended prior to treatment in patients with risk factors for ONJ such as invasive dental procedures (eg, tooth extraction, dental implants, oral surgery), diagnosis of cancer, concomitant therapies (eg, chemotherapy, corticosteroids, angiogenesis inhibitors), poor oral hygiene, and co-morbid disorders (eg, periodontal and/or other pre-existing dental disease, anemia, coagulopathy, infection, ill-fitting dentures). Good oral hygiene practices should be maintained during treatment with BILDYOS. Concomitant administration of drugs associated with ONJ may increase the risk of developing ONJ. The risk of ONJ may increase with duration of exposure to denosumab products.
For patients requiring invasive dental procedures, clinical judgment of the treating physician and/or oral surgeon should guide the management plan of each patient based on individual benefit-risk assessment.
Patients who are suspected of having or who develop ONJ while on BILDYOS should receive care by a dentist or an oral surgeon. Extensive dental surgery to treat ONJ may exacerbate the condition. Discontinuation of BILDYOS should be considered based on individual benefit-risk assessment.
Atypical low-energy, or low trauma fractures of the shaft have been reported in patients receiving denosumab products. Causality has not been established as these fractures also occur in osteoporotic patients who have not been treated with antiresorptive agents.
During BILDYOS treatment, patients should be advised to report new or unusual thigh, hip, or groin pain. Any patient who presents with thigh or groin pain should be suspected of having an atypical fracture and should be evaluated to rule out an incomplete femur fracture. Interruption of BILDYOS therapy should be considered, pending a benefit-risk assessment, on an individual basis.
Following discontinuation of denosumab treatment, fracture risk increases, including the risk of multiple vertebral fractures. New vertebral fractures occurred as early as 7 months (on average 19 months) after the last dose of denosumab. Prior vertebral fracture was a predictor of multiple vertebral fractures after denosumab product discontinuation. Evaluate an individual’s benefit-risk before initiating treatment. If BILDYOS treatment is discontinued, patients should be transitioned to an alternative antiresorptive therapy.
In a clinical trial of over 7800 women with postmenopausal osteoporosis, serious infections leading to hospitalization were reported more frequently in the denosumab group than in the placebo group. Serious skin infections, as well as infections of the abdomen, urinary tract, and ear, were more frequent in patients treated with denosumab products. Endocarditis was also reported more frequently in denosumab-treated patients. The incidence of opportunistic infections and the overall incidence of infections were similar between the treatment groups. Advise patients to seek prompt medical attention if they develop signs or symptoms of severe infection, including cellulitis.
Patients on concomitant immunosuppressant agents or with impaired immune systems may be at increased risk for serious infections. Consider the benefit-risk profile in such patients before treating with BILDYOS. In patients who develop serious infections while on BILDYOS, prescribers should assess the need for continued BILDYOS therapy.
In a clinical trial of over 7800 women with postmenopausal osteoporosis, epidermal and dermal adverse events such as dermatitis, eczema, and rashes occurred at a significantly higher rate with denosumab treatment compared to placebo. Most of these events were not specific to the injection site. Consider discontinuing BILDYOS if severe symptoms develop.
In postmarketing experience, severe and occasionally incapacitating bone, joint, and/or muscle pain has been reported in patients during denosumab treatment. Onset of symptoms varied from one day to several months after starting denosumab products. Consider discontinuing use if severe symptoms develop.
In clinical trials in women with postmenopausal osteoporosis, treatment with denosumab resulted in significant suppression of bone remodeling as evidenced by markers of bone turnover and bone histomorphometry. The significance of these findings and the effect of long-term treatment with denosumab products are unknown. Monitor patients for consequences, including ONJ, atypical fractures, and delayed fracture healing.
BILDYOS is not approved for use in pediatric patients. Hypercalcemia has been reported in pediatric patients with osteogenesis imperfecta treated with denosumab products.
The most common adverse reactions (>5% and more common than placebo) reported with denosumab products in women with postmenopausal osteoporosis are back pain, pain in extremity, musculoskeletal pain, hypercholesterolemia, and cystitis.
The most common adverse reactions (>5% and more common than placebo) reported with denosumab products in men with osteoporosis are back pain, arthralgia, and nasopharyngitis. Pancreatitis has been reported with denosumab products.
The most common adverse reactions (>3% and more common than active-control group) reported with denosumab products in patients with glucocorticoid-induced osteoporosis are back pain, hypertension, bronchitis, and headache.
The most common (per patient incidence ≥10%) adverse reactions reported with denosumab products in patients with bone loss receiving androgen deprivation therapy for prostate cancer or adjuvant aromatase inhibitor therapy for breast cancer are arthralgia and back pain. Pain in extremity and musculoskeletal pain have also been reported in clinical trials.
The most common adverse reactions leading to discontinuation of denosumab products in patients with postmenopausal osteoporosis are back pain and constipation.
Denosumab is a human monoclonal antibody. As with all therapeutic proteins, there is potential for immunogenicity.
Before prescribing BILDYOS, please read the Prescribing Information, including the Boxed Warning about severe hypocalcemia. The Medication Guide also is available.
Please note, BILDYOS is part of the Risk Evaluation and Mitigation Strategy (REMS) program.
References:
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15. Data on File. Organon group of companies.
16. Li N, Chu N, Zhu L, et al. Pharmacokinetics, pharmacodynamics, safety, and immunogenicity of HLX14 versus reference denosumab in healthy males: a randomized phase I study. Clin Transl Sci. 2024;17(12):e70089. doi:10.1111/cts.70089
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PROLIA is a trademark registered in the US by Amgen Inc.; Organon is not associated with this trademark owner.
