Budapest, Hungary and London, UK, 29 September 2025 – Gedeon Richter Plc. (“Richter”) and Hikma Pharmaceuticals Plc. along with its wholly owned subsidiary Hikma Pharmaceuticals USA Inc. (“Hikma”) announce today that the U.S. Food and Drug Administration (FDA) has granted approval for the Biologics License Applications (BLA) of their biosimilar denosumab products, EnobyTM (denosumab-qbde) and XtrenboTM (denosumab-qbde), referencing Prolia® and Xgeva® respectively. 

Denosumab is indicated for treating osteoporosis in postmenopausal women, preventing skeletal-related complications in cancer that has spread to the bone, and treating unresectable giant cell tumor of the bone. 

The FDA approval of EnobyTM, originally known as RGB-14-P and XtrenboTM, originally known as RGB- 14-X, was based on a comprehensive analytical, non-clinical, and clinical data package submitted by Hikma to the FDA. The content of the BLA demonstrated that EnobyTM and XtrenboTM have similar quality, efficacy, safety and immunogenicity as the reference denosumab products Prolia® and Xgeva® respectively.

Hikma and Richter entered into a license and commercialization agreement for RGB-14 in December 2021. Under the terms of the agreement, Richter is responsible for the development and manufacture of the products, and Hikma is responsible for the FDA registration and exclusive commercialization in the US.

“We are proud to be able to bring these biosimilar options to healthcare providers and patients, improving affordability and access to these important therapies,” said Dr. Bill Larkins, President of Hikma Injectables. “We are a top-three US provider of sterile injectable medicines to US hospitals and we will use our strong and well-established commercial capabilities to bring these products to patients.” 

“The approvals of EnobyTM and XtrenboTM represent a significant milestone accomplishment for Richter, as our first FDA approved biosimilars. They are a testimony to Richter’s ambition in providing affordable biosimilar access in important therapies to patients across the globe and establishing Richter as a high quality biosimilar developer and manufacturer.” said Dr. Erik Bogsch, Head of Biotechnology Business Unit at Richter.

About EnobyTM and XtrenboTM (denosumab-qbde) 

Both EnobyTM and XtrenboTM contain denosumab, a human monoclonal antibody (IgG2) that targets and binds with high affinity to RANKL, inhibiting its interaction with the RANK receptor on osteoclasts and their precursors. This mechanism prevents osteoclast formation, function, and survival, thereby reducing bone resorption in both cortical and trabecular bone. The products are administered subcutaneously, with dosing regimens and presentations identical to those of the reference medicines.

HIGHLIGHTS OF PRESCRIBING INFORMATION 
These highlights do not include all the information needed to use ENOBY™ safely and effectively. See full prescribing information for ENOBY. 
ENOBY™ (denosumab-qbde) injection, for subcutaneous use 
ENOBY™ (denosumab-qbde) is biosimilar* to PROLIA® (denosumab).

BOXED WARNING: SEVERE HYPOCALCEMIA IN PATIENTS WITH ADVANCED KIDNEY DISEASE

See full prescribing information for complete boxed warning.

• Patients with advanced chronic kidney disease 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. (5.1)
• The presence of chronic kidney disease-mineral bone disorder (CKD- MBD) markedly increases the risk of hypocalcemia. (5.1)
• Prior to initiating Enoby in patients with advanced chronic kidney disease, evaluate for the presence of CKD-MBD. Treatment with Enoby in these patients should be supervised by a healthcare provider with expertise in the diagnosis and management of CKD-MBD. (2.2, 5.1)

 

-------------------------------INDICATIONS AND USAGE------------------------

 

Enoby is a RANK ligand (RANKL) inhibitor indicated for treatment:

• of postmenopausal women with osteoporosis at high risk for fracture (1.1)
• to increase bone mass in men with osteoporosis at high risk for fracture (1.2)
• of glucocorticoid-induced osteoporosis in men and women at high risk for fracture (1.3)
• to increase bone mass in men at high risk for fracture receiving androgen deprivation therapy for nonmetastatic prostate cancer (1.4)
• to increase bone mass in women at high risk for fracture receiving adjuvant aromatase inhibitor therapy for breast cancer (1.5)

 

------------------------DOSAGE AND ADMINISTRATION----------------------

 

• Pregnancy must be ruled out prior to administration of Enoby. (2.1)
• Before initiating Enoby in patients with advanced chronic kidney disease, including dialysis patients, evaluate for the presence of chronic kidney disease mineral and bone disorder with intact parathyroid hormone, serum calcium, 25(OH) vitamin D, and 1,25(OH)2 vitamin D. (2.2, 5.1, 8.6)
• Enoby should be administered by a healthcare provider. (2.3)
• Administer 60 mg every 6 months as a subcutaneous injection in the upper arm, upper thigh, or abdomen. (2.3)
• Instruct patients to take calcium 1000 mg daily and at least 400 IU vitamin D daily. (2.3)

 

-----------------------DOSAGE FORMS AND STRENGTHS--------------------

 

• Injection: 60 mg/mL solution in a single-dose prefilled syringe (3)

 

------------------------------CONTRAINDICATIONS-------------------------------

 

• Hypocalcemia (4, 5.1)
• Pregnancy (4, 8.1)
• Known hypersensitivity to denosumab products (4, 5.3)

 

---------------------- WARNINGS AND PRECAUTIONS-------------------

 

• Hypocalcemia: Pre existing hypocalcemia must be corrected before initiating Enoby. May worsen, especially in patients with renal impairment. Adequately supplement all patients with calcium and vitamin D. Concomitant use of calcimimetic drugs may also worsen hypocalcemia risk. Evaluate for presence of chronic kidney disease mineral bone disorder. Monitor serum calcium. (5.1)
• Same Active Ingredient: Patients receiving Enoby should not receive other denosumab products concomitantly. (5.2)
• Hypersensitivity including anaphylactic reactions may occur. Discontinue permanently if a clinically significant reaction occurs. (5.3)
• Osteonecrosis of the jaw: Has been reported with denosumab products. Monitor for symptoms. (5.4)
• Atypical femoral fractures: Have been reported. Evaluate patients with thigh or groin pain to rule out a femoral fracture. (5.5)
• Multiple vertebral fractures have been reported following treatment discontinuation. Patients should be transitioned to another antiresorptive agent if Enoby is discontinued. (5.6)
• Serious infections including skin infections: May occur, including those leading to hospitalization. Advise patients to seek prompt medical attention if they develop signs or symptoms of infection, including cellulitis. (5.7)
• Dermatologic reactions: Dermatitis, rashes, and eczema have been reported. Consider discontinuing Enoby if severe symptoms develop. (5.8)
• Severe bone, joint, muscle pain may occur. Discontinue use if severe symptoms develop. (5.9)
• Suppression of bone turnover: Significant suppression has been demonstrated. Monitor for consequences of bone over-suppression. (5.10)

 

----------------------------ADVERSE REACTIONS---------------------------------

 

• Postmenopausal osteoporosis: Most common adverse reactions (> 5% and more common than placebo) were: back pain, pain in extremity, hypercholesterolemia, musculoskeletal pain, and cystitis. Pancreatitis has been reported in clinical trials. (6.1)
• Male osteoporosis: Most common adverse reactions (> 5% and more common than placebo) were: back pain, arthralgia, and nasopharyngitis. (6.1)
• Glucocorticoid-induced osteoporosis: Most common adverse reactions (> 3% and more common than active-control group) were: back pain, hypertension, bronchitis, and headache. (6.1)
• Bone loss due to hormone ablation for cancer: Most common adverse reactions (≥ 10% and more common than placebo) were: arthralgia and back pain. Pain in extremity and musculoskeletal pain have also been reported in clinical trials. (6.1)

To report SUSPECTED ADVERSE REACTIONS, contact Hikma Pharmaceuticals USA Inc. at 1-877- 845-0689 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

 

-----------------------USE IN SPECIFIC POPULATIONS------------------------

 

• Pregnant women and females of reproductive potential: Denosumab products may cause fetal harm when administered to pregnant women. Advise females of reproductive potential to use effective contraception during therapy, and for at least 5 months after the last dose of Enoby. (8.1, 8.3)
• Pediatric patients: Enoby is not approved for use in pediatric patients. (8.4)
• Renal impairment: No dose adjustment is necessary in patients with renal impairment. Patients with advanced chronic kidney disease (eGFR

<30 mL/min/1.73 m2), including dialysis-dependent patients, are at greater risk of severe hypocalcemia. The presence of underlying chronic kidney disease-mineral bone disorder markedly increases the risk of hypocalcemia. (5.1, 8.6)

See 17 for PATIENT COUNSELING INFORMATION and Medication Guide.

*Biosimilar means that the biological product is approved based on data demonstrating that it is highly similar to an FDA-approved biological product, known as a reference product, and that there are no clinically meaningful differences between the biosimilar product and the reference product. Biosimilarity of ENOBY has been demonstrated for the condition(s) of use (e.g., indication(s), dosing regimen(s)), strength(s), dosage form(s), and route(s) of administration described in its Full Prescribing Information.

HIGHLIGHTS OF PRESCRIBING INFORMATION

These highlights do not include all the information needed to use XTRENBO™ safely and effectively. See full prescribing information for XTRENBO.

XTRENBO™ (denosumab-qbde) injection, for subcutaneous use

XTRENBO™ (denosumab-qbde) is biosimilar* to XGEVA® (denosumab).

 

---------------------------INDICATIONS AND USAGE----------------------------

 

Xtrenbo is a RANK ligand (RANKL) inhibitor indicated for:

• Prevention of skeletal-related events in patients with multiple myeloma and in patients with bone metastases from solid tumors. (1.1)
• Treatment of adults and skeletally mature adolescents with giant cell tumor of bone that is unresectable or where surgical resection is likely to result in severe morbidity. (1.2, 14.3)
• Treatment of hypercalcemia of malignancy refractory to bisphosphonate therapy. (1.3)

 

-----------------------DOSAGE AND ADMINISTRATION-----------------------

 

• Xtrenbo should be administered by a healthcare provider. (2.1)
• Xtrenbo is intended for subcutaneous route only and should not be administered intravenously, intramuscularly, or intradermally. (2.1)
• Multiple Myeloma and Bone Metastasis from Solid Tumors: Administer 120 mg every 4 weeks as a subcutaneous injection in the upper arm, upper thigh, or abdomen. (2.2)
• Giant Cell Tumor of Bone: Administer 120 mg every 4 weeks with additional 120 mg doses on Days 8 and 15 of the first month of therapy. Administer subcutaneously in the upper arm, upper thigh, or abdomen. (2.3)
• Administer calcium and vitamin D as necessary to treat or prevent hypocalcemia. (2.2, 2.3)
• Hypercalcemia of Malignancy: Administer 120 mg every 4 weeks with additional 120 mg doses on Days 8 and 15 of the first month of therapy. Administer subcutaneously in the upper arm, upper thigh, or abdomen. (2.4)

 

----------------------DOSAGE FORMS AND STRENGTHS---------------------

 

• Injection: 120 mg/1.7 mL (70 mg/mL) solution in a single-dose vial (3)

 

--------------------------CONTRAINDICATIONS----------------------------------

 

• Hypocalcemia (4.1)
• Known clinically significant hypersensitivity to denosumab products (4.2)

 

-------------------------WARNINGS AND PRECAUTIONS----------------------

 

• Drug Products with Same Active Ingredient: Patients receiving Xtrenbo should not receive other denosumab products concomitantly. (5.1)
• Hypersensitivity reactions including anaphylaxis may occur. Discontinue permanently if a clinically significant reaction occurs. (5.2)
• Hypocalcemia: Denosumab products can cause severe symptomatic hypocalcemia. Fatal cases have been reported with denosumab products use. Correct hypocalcemia prior to initiating Xtrenbo. Monitor calcium levels during therapy, especially in the first weeks of initiating therapy, and adequately supplement all patients with calcium and vitamin D. (5.3)
• Osteonecrosis of the jaw (ONJ) has been reported in patients receiving denosumab products. Perform an oral examination prior to starting Xtrenbo. Monitor for symptoms. Avoid invasive dental procedures during treatment with Xtrenbo. (5.4)
• Atypical femoral fracture: Evaluate patients with thigh or groin pain to rule out a femoral fracture. (5.5)
• Hypercalcemia Following Treatment Discontinuation in Patients with Giant Cell Tumor of Bone and in Patients with Growing Skeletons: Monitor patients for signs and symptoms of hypercalcemia, and manage as clinically appropriate. (5.6, 8.4)
• Multiple Vertebral Fractures (MVF) Following Treatment Discontinuation: When Xtrenbo treatment is discontinued, evaluate the individual patient’s risk for vertebral fractures. (5.7)
• Embryo-Fetal Toxicity: Can cause fetal harm. Advise females of reproductive potential of potential risk to the fetus and to use effective contraception. (5.8, 8.1, 8.3)

 

--------------------------------ADVERSE REACTIONS-----------------------------

 

• Bone Metastasis from Solid Tumors: Most common adverse reactions (≥ 25%) were fatigue/asthenia, hypophosphatemia, and nausea. (6.1)
• Multiple Myeloma: Most common adverse reactions (≥ 10%) were diarrhea, nausea, anemia, back pain, thrombocytopenia, peripheral edema, hypocalcemia, upper respiratory tract infection, rash, and headache. (6.1)
• Giant Cell Tumor of Bone: Most common adverse reactions (≥ 10%) were arthralgia, headache, nausea, back pain, fatigue, and pain in extremity. (6.1)
• Hypercalcemia of Malignancy: Most common adverse reactions (> 20%) were nausea, dyspnea, decreased appetite, headache, peripheral edema, vomiting, anemia, constipation, and diarrhea. (6.1)

To report SUSPECTED ADVERSE REACTIONS, contact Hikma Pharmaceuticals USA Inc. at 1-877- 845-0689 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

 

-------------------------USE IN SPECIFIC POPULATIONS----------------------

 

• Pediatric patients: Recommended only for treatment of skeletally mature adolescents with giant cell tumor of bone. (8.4)Renal impairment: Patients with creatinine clearance less than 30 mL/min or receiving dialysis are at risk for hypocalcemia. Adequately supplement with calcium and vitamin D. (8.6)

 

See 17 for PATIENT COUNSELING INFORMATION

*Biosimilar means that the biological product is approved based on data demonstrating that it is highly similar to an FDA-approved biological product, known as a reference product, and that there are no clinically meaningful differences between the biosimilar product and the reference product. Biosimilarity of XTRENBO has been demonstrated for the condition(s) of use (e.g., indication(s), dosing regimen(s)), strength(s), dosage form(s), and route(s) of administration described in its Full Prescribing Information.

 

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