FDA Accepts BLA for Denosumab Biosimilar

The FDA has accepted Organon and Shanghai Henlius Biotech’s biologics license application for HLX14, a denosumab (PROLIA/XGEVA) biosimilar.¹

Denosumab is FDA-approved to treat postmenopausal women at high risk for fracture, patients with intolerance or inadequate response to other osteoporosis treatments, and patients who will be taking corticosteroids for ≥6 months and are at a high risk for fracture. The drug is also used to increase bone mass in men with osteoporosis at a high risk for fracture and men at a high risk for fracture treated with certain medications for prostate cancer.²

The BLA is based on data from comparative quality analytical studies and 2 clinical studies, among other head-to-head studies for HLX14. One such study was a 2-part phase 1 clinical study in Chinese healthy adult male participants with the first part being an open-label, randomized, parallel-controlled, single-dose, pilot study comparing the pharmacokinetic parameters of HLX14 and PROLIA after subcutaneous and the second part a double-blind, randomized, parallel-controlled, single-dose, 4-arm study comparing the pharmacokinetic similarity of HLX14 with PROLIA after subcutaneous injection. Another study was a randomized, double-blind, international multicenter, parallel-controlled phase 3 clinical study comparing the efficacy, safety, tolerability, and immunogenicity of HLX14 with reference PROLIA in postmenopausal women with osteoporosis at high risk for fracture.¹

Organon was granted exclusive commercialization rights to HLX14 and another biosimilar candidate in a 2022 a license and supply agreement with Henlius in markets markets such as the United States, the European Union, and Canada, but not China.

The FDA approved the first denosumab biosimilars, 2 formulations of denosumab-bddz marketed under the names Wyost and Jubbonti, in March 2024.³ Wyost is a denosumab-bddz 120 mg/1.7 mL (70 mg/mL) injection approved to reduce the risk of skeletal-related events (SREs) in patients with multiple myeloma and for those with bone metastases from solid tumors, to treat adult patients with skeletally mature adolescents with giant cell tumor of bone which is unresectable or where surgical resection is likely to result in severe morbidity, and to treat hypercalcemia of malignancy refractory to bisphosphonate therapy.

Jubbonti is a 60 mg/1 mL injection of the denosumab-bbdz is approved to treat postmenopausal women with osteoporosis who are at a high risk for fracture, to increase bone mass in men with osteoporosis who are at a high risk for fracture, and to increase bone mass in men at high risk for fracture who are being treated with androgen deprivation therapy for nonmetastatic prostate cancer. It is also approved to treat glucocorticoid-induced osteoporosis and to increase bone mass in women at high risk for fracture who are being treated with adjuvant aromatase inhibitor therapy for breast cancer.

“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,” said Keren Haruvi, President Sandoz North America, in a statement.³ “I am proud that Sandoz continues to pioneer access to these life-changing medicines for the patients who need them most."

REFERENCES

1. US FDA Accepts Biologics License Application (BLA) for HLX14, Biosimilar Candidate of PROLIA/XGEVA (denosumab). News release. Organon. October 30, 2024. https://www.businesswire.com/news/home/20241029648679/en/US-FDA-Accepts-Biologics-License-Application-BLA-for-HLX14-Biosimilar-Candidate-of-PROLIAXGEVA-denosumab

2. Prolia (denosumab): Other approved indications. Prolia.com. (n.d.). https://www.prolia.com/proven-prolia-results/other-approved-indications

3. Sandoz International GmbH. Sandoz receives FDA approval for first and only denosumab biosimilars. GlobeNewswire News Room. 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.