Sandoz receives FDA approval for first and only denosumab biosimilars

MEDIA RELEASE

• Wyost^® (denosumab-bddz) and Jubbonti^® (denosumab-bddz) interchangeable with and approved by FDA for all indications of reference medicines Xgeva ^®* (denosumab) and Prolia^®* (denosumab)
• FDA approval based on robust clinical studies and totality of evidence, which show no clinically meaningful differences from reference medicines

Basel, March 5, 2024 – Sandoz, the global leader in generic and biosimilar medicines, today announced that the US Food and Drug Administration (FDA) approved Wyost^® (denosumab-bbdz) and Jubbonti^® (denosumab-bbdz), the first and only FDA-approved denosumab biosimilars, to treat all indications of the reference medicines.

Keren Haruvi, President Sandoz North America, said: "Sandoz has achieved the first FDA approval for biosimilars to denosumab, a medicine that can address primary and secondary bone loss, such as osteoporosis, as well as cancer-related skeletal events, which are disease states that can profoundly reduce quality of life for patients. I am proud that Sandoz continues to pioneer access to these life-changing medicines for the patients who need them most."

Wyost^® is approved to prevent skeletal-related events (SREs) in patients with multiple myeloma and in patients with bone metastases from solid tumors, to treat 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, and to treat hypercalcemia of malignancy refractory to bisphosphonate therapy.¹

Bone is the third most frequent site for metastatic tumors.² Nearly all types of cancer can spread to the bone and cause pain and fractures, though cancers that often metastasize in bones include breast and prostate.³

Jubbonti^® is approved to treat postmenopausal women with osteoporosis at high risk for fracture, to increase bone mass in men with osteoporosis at high risk for fracture, to treat glucocorticoid-induced osteoporosis in men and women at high risk for fracture, to increase bone mass in men at high risk for fracture receiving androgen deprivation therapy for nonmetastatic prostate cancer, and to increase bone mass in women at high risk for fracture receiving adjuvant aromatase inhibitor therapy for breast cancer.⁴

Osteoporosis is a bone disease that develops when bone mineral density and bone mass decrease or when bone strength and structure change. People living with osteoporosis typically do not have symptoms and might not know they have the disease until they experience a fracture. More than 10 million US adults aged 50 and over live with osteoporosis, a major cause of fractures in postmenopausal women and in older men.^5,6 Half of all women over the age of 50 will experience an osteoporotic fracture during their lifetime.⁷

The FDA approval is based on robust clinical studies and accompanied by labeling with safety warnings. The Jubbonti^® approval is also accompanied by approval of Sandoz’s Jubbonti^® Risk Evaluation and Mitigation Strategy (REMS) program, which is designed to inform prescribers and patients about the risk of severe hypocalcemia associated with Jubbonti^® in patients with advanced chronic kidney disease, including dialysis-dependent patients.

Wyost^® and Jubbonti^® have the same dosage form, route of administration, dosing regimen and presentation as the respective reference medicines. Wyost^® and Jubbonti^® are approved as interchangeable with the reference medicines for all indications.

Given ongoing patent litigation around these products, Sandoz will not comment on anticipated launch timing or other launch details at this time.

About Wyost^® (denosumab-bbdz)
Wyost^® 120 mg/1.7 mL (70 mg/mL) injection has been approved by the FDA as interchangeable with the reference medicine, a human monoclonal antibody designed to bind to the RANKL protein, an activator of osteoclasts (cells involved in breaking down bone tissue).^8,9 Wyost^® is indicated in the US to prevent SREs in patients with multiple myeloma and in patients with bone metastases from solid tumors, to treat 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, and to treat hypercalcemia of malignancy refractory to bisphosphonate therapy.¹

SELECT IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS
Hypocalcemia and known clinically significant hypersensitivity to denosumab products.

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

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

USE IN SPECIFIC POPULATIONS
Pediatric patients: Recommended only for treatment of skeletally mature adolescents with giant cell tumor of bone. 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.

This is not the complete list of all the safety information for Wyost. Please click to see full Prescribing Information for Wyost.

About Jubbonti^® (denosumab-bbdz)
Jubbonti^® 60 mg/1 mL injection has been approved by the FDA as interchangeable with the reference medicine, a human monoclonal antibody designed to bind to the RANKL protein, an activator of osteoclasts (cells involved in breaking down bone tissue).^8,9 Jubbonti^® is indicated in the US to treat postmenopausal women with osteoporosis at high risk for fracture, to increase bone mass in men with osteoporosis at high risk for fracture, to treat glucocorticoid-induced osteoporosis in men and women at high risk for fracture, to increase bone mass in men at high risk for fracture receiving androgen deprivation therapy for nonmetastatic prostate cancer, and to increase bone mass in women at high risk for fracture receiving adjuvant aromatase inhibitor therapy for breast cancer.⁴

SELECT IMPORTANT SAFETY INFORMATION

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 risk of severe hypocalcemia following denosumab products administration. Severe hypocalcemia requiring 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. Prior to initiating Jubbonti in patients with advanced chronic kidney disease, evaluate for the presence of CKD-MBD. Treatment with Jubbonti in these patients should be supervised by a healthcare provider with expertise in the diagnosis and management of CKD-MBD.

CONTRAINDICATIONS
Hypocalcemia; pregnancy; and known hypersensitivity to denosumab products.

WARNINGS AND PRECAUTIONS
Hypocalcemia: Pre-existing hypocalcemia must be corrected before initiating Jubbonti. 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. Same Active Ingredient: Patients receiving Jubbonti should not receive other denosumab products concomitantly. Hypersensitivity including anaphylactic reactions may occur. Discontinue permanently if a clinically significant reaction occurs. Osteonecrosis of the jaw (ONJ): Has been reported with denosumab products. Monitor for symptoms. Atypical femoral fractures: Have been reported. Evaluate patients with thigh or groin pain to rule out a femoral fracture. Multiple vertebral fractures have been reported following treatment discontinuation. Patients should be transitioned to another antiresorptive agent if Jubbonti is discontinued. 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. Dermatologic reactions: Dermatitis, rashes, and eczema have been reported. Consider discontinuing Jubbonti if severe symptoms develop. Severe bone, joint, muscle pain may occur. Discontinue use if severe symptoms develop. Suppression of bone turnover: Significant suppression has been demonstrated. Monitor for consequences of bone over-suppression.

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. Male osteoporosis: Most common adverse reactions (> 5% and more common than placebo) were: back pain, arthralgia, and nasopharyngitis. Glucocorticoid-induced osteoporosis: Most common adverse reactions (> 3% and more common than active-control group) were: back pain, hypertension, bronchitis, and headache. 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.

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 Jubbonti. Pediatric patients: Denosumab products are not approved for use in pediatric patients. 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.

This is not the complete list of all the safety information for Jubbonti. Please click to see full Prescribing Information for Jubbonti.

References
1.   Wyost^®. Prescribing Information. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/761362s000lbl.pdf [Last accessed: March 2024]
2.   Bone Metastasis. Apoorva Jayarangaiah; Alysia K. Kemp; Pramod Theetha Kariyann, Oct 25 2022. Available at https://www.ncbi.nlm.nih.gov/books/NBK507911/#:~:text=The%20skeleton%20is%20the%20third,metastasize%20to%20bone%20as%20well. [Last accessed: March 2024]
3.   American Cancer Society. Bone Metastases. Available at: https://www.cancer.org/treatment/understanding-your-diagnosis/advanced-cancer/bone-metastases.html [Last accessed: March 2024]
4.   Jubbonti^®. Prescribing Information. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/761362s000lbl.pdf [Last accessed: March 2024]
5.   National Institute of Arthritis and Musculoskeletal and Skin Diseases. Osteoporosis. 2022. Available at: https://www.niams.nih.gov/health-topics/osteoporosis [Last accessed: March 2024]
6.   National Center for Health Statistics. Osteoporosis or Low Bone Mass in Older Adults: United States, 2017–2018. 2021. Available at: https://www.cdc.gov/nchs/products/databriefs/db405.htm [Last accessed: March 2024]
7.   Bone Health and Osteoporosis Foundation. Osteoporosis Fast Facts. Available at: https://www.bonehealthandosteoporosis.org/wp-content/uploads/Osteoporosis-Fast-Facts-2.pdf [Last accessed: March 2024]
8.   Amgen Inc. Prolia^® (Denosumab): Prescribing Information. Available at: https://www.pi.amgen.com/-/media/Project/Amgen/Repository/pi-amgen-com/Prolia/prolia_pi.pdf [Last accessed: March 2024]
9.   Amgen Inc. Xgeva^® (Denosumab): Prescribing Information. Available at: https://www.pi.amgen.com/-/media/Project/Amgen/Repository/pi-amgen-com/xgeva/xgeva_pi.pdf [Last accessed: March 2024]

*Xgeva^® and Prolia^® are registered trademarks of Amgen Inc.

Disclaimer
This Media Release contains forward-looking statements, which offer no guarantee with regard to future performance. These statements are made on the basis of management’s views and assumptions regarding future events and business performance at the time the statements are made. They are subject to risks and uncertainties including, but not confined to, future global economic conditions, exchange rates, legal provisions, market conditions, activities by competitors and other factors outside of the control of Sandoz. Should one or more of these risks or uncertainties materialize or should underlying assumptions prove incorrect, actual outcomes may vary materially from those forecasted or expected. Each forward-looking statement speaks only as of the date of the particular statement, and Sandoz undertakes no obligation to publicly update or revise any forward-looking statements, except as required by law.

About Sandoz
Sandoz (SIX: SDZ; OTCQX: SDZNY) is the global leader in generic and biosimilar medicines, with a growth strategy driven by its Purpose: pioneering access for patients. 22,000 people of more than 100 nationalities work together to bring Sandoz medicines to some 500 million patients worldwide, generating substantial global healthcare savings and an even larger total social impact. Its leading portfolio of more than 1500 products addresses diseases from the common cold to cancer. Headquartered in Basel, Switzerland, Sandoz traces its heritage back to the year 1886. Its history of breakthroughs includes Calcium Sandoz in 1929, the world’s first oral penicillin in 1951, and the first biosimilar in 2006. In 2022, Sandoz achieved sales of USD 9.1 billion and core EBITDA of USD 1.9 billion.

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• Media Release Deno FDA Approval 24-03-05

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