Two Biosimilars to Denosumab Win FDA Approval as Amgen and Sandoz Go to Court

The FDA has approved the first 2 biosimilars for denosumab (Prolia and Xgeva; Amgen).¹ Wyost/Jubbonti (denosumab-bddz; Sandoz) were also approved as interchangeable biosimilars for all indications of the reference products.

While Jubbonti was approved in Canada last month, no denosumab biosimilars have been approved yet in the European Union.² Similar to the reference products, the 2 biosimilars are approved for different indications.

Denosumab products are human monoclonal antibodies that bind to the RANKL protein to prevent the RANK receptor on the surface of osteoclasts from activating, which causes osteoclastic bone resorption.

Wyost is a biosimilar of Xgeva and indicated:

• To prevent skeletal-related events in patients with multiple myeloma and in patients with bone metastases from solid tumors
• In 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
• For hypercalcemia of malignancy refractory to bisphosphonate therapy

Jubbonti is a biosimilar of Prolia and indicated:

• In 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
• To increase bone mass in women at high risk for fracture receiving adjuvant aromatase inhibitor therapy for breast cancer

The approval is accompanied by safety warnings and Jubbonti has a Risk Evaluation and Mitigation Strategy program, which informs prescribers and patients about the risk of severe hypocalcemia associated with the product in patients with advanced chronic kidney disease.

On February 1, 2024, the FDA added a Boxed Warning for Prolia, noting that patients on dialysis or with mineral and bone disorder were at the highest risk.³

Sandoz and Amgen are locked in ongoing litigation. The maker of the reference product claims the biosimilars infringe on 21 patents covering Prolia and Xgeva. Amgen is asking the court to determine that Sandoz infringed on one or more of the patents and for “a permanent injunction against the commercial manufacture, use, offer to sell, or sale within the United States or importation into the United States of Defendants’ denosumab biosimilar product(s) before the expiration of each of the Patents-In-Suit that are found infringed.”

One of the patents named in the lawsuit does not expire until 2037.

According to Amgen’s full year 2023 financial results,⁴ sales of Prolia increased 12% over the previous year with US sales of $2.7 billion in 2023. Sales of Xgeva increased 5% over the previous year with US sales of $1.5 billion in 2023.

Prolia sales are second only to etanercept (Enbrel) for Amgen, which faces biosimilar competition in 2029. The same court reviewing Amgen’s lawsuit against Sandoz decided in 2021 that etanercept biosimilars can’t come to market until 2029, which would grant Amgen 3 decades of product exclusivity for Enbrel.⁵

References

1. Sandoz receives FDA approval for first and only denosumab biosimilars. News release. Sandoz. March 5, 2024. Accessed March 5, 2024. https://www.globenewswire.com/news-release/2024/03/05/2840809/0/en/Sandoz-receives-FDA-approval-for-first-and-only-denosumab-biosimilars.html

2. Jeremias S. FDA approves first denosumab biosimilar. The Center for Biosimilars®. March 5, 2024. Accessed March 5, 2024. https://www.centerforbiosimilars.com/view/fda-approves-first-denosumab-biosimilar

3. FDA adds Boxed Warning for increased risk of severe hypocalcemia in patients with advanced chronic kidney disease taking osteoporosis medicine Prolia (denosumab). News release. FDA. February 1, 2024. Accessed March 5, 2024. https://www.fda.gov/drugs/drug-safety-and-availability/fda-adds-boxed-warning-increased-risk-severe-hypocalcemia-patients-advanced-chronic-kidney-disease

4. Amgen reports fourth quarter and full year 2023 financial results. . News release. Amgen. February 6, 2024. Accessed March 5, 2024. https://www.amgen.com/newsroom/press-releases/2024/02/amgen-reports-fourth-quarter-and-full-year-2023-financial-results

5. Hagen T. NJ court decision means 3 decades of product exclusivity for Enbrel. The Center for Biosimilars. December 1, 2021. Accessed March 5, 2024. https://www.centerforbiosimilars.com/view/nj-court-decision-means-3-decades-of-product-exclusivity-for-enbrel