Denosumab Biosimilar Shows "Promising" Efficacy, Equivalency in Phase 3 Trial


A phase 3 trial comparing QL1206, a denosumab biosimilar, to the reference agent has returned results demonstrating the efficacy, safety, and pharmacokinetic equivalency of the biosimilar to the reference agent.

Li Zhang, MD | Credit: American Society of Clinical Oncology

Li Zhang, MD
Credit: American Society of Clinical Oncology

Data from a phase 3 trial comparing QL1206, a denosumab biosimilar, to denosumab details what investigators describe as “promising” efficacy, safety, and pharmacokinetics equivalency to the reference agent.

Results of the study, which included more than 700 patients from 51 centers in China, indicate the bio similar and reference groups experienced median percentage changes of -75.2% and -75.8%, respectively, for urinary N-telopeptide/creatinine ratio (uNTX/uCr) and adverse events, immunogenicity, and pharmacokinetics were similar between the groups.1

“As the first denosumab biosimilar, QL1206 has promising clinical efficacy in the reduction of uNTX/uCr, s-BALP, and the risk of SREs, and a tolerable safety profile, immunogenicity, and PK similar to denosumab. Switching from denosumab to QL1206 is feasible. QL1206 is an option for patients with bone metastases from solid tumors,” wrote investigators.1

The advent of biosimilars has brought forth new promise of increased equity and improved access to care for a slew of conditions, ranging from rheumatic to gastrointestinal disease and even crossing into the field of ophthalmology.2,3,4 In the current study, a team of investigators led by Li Zhang, MD, director of the Medical Oncology Department of Sun Yat-Sen University, sought to evaluate the potential utility of a denosumab bio similar relative to the reference agent in patients with solid tumors and bone metastases. Patients included in the randomized, double-blind, phase 3 trial were recruited from 51 centers in China. For inclusion, patients were required to be between the ages of 18-80 years and have an Eastern Cooperative Oncology Group performance status of 0-2 when eligible.1

Per trial protocol, the treatment period was divided into 2 parts: a 13-week double-blind period followed by a 40-week open-label period. The trial’s safety follow-up lasted 20 weeks. Patients were randomized in a 1:1 ratio to receive 3 doses of QL1206 or reference denosumab, with these groups stratified based on tumor type previous skeletal-related events, and current systemic anti-tumor therapy.During the double-blind portion of the study, patients received 3 doses or QL1206 o0r reference denosumab every 4 weeks. During the open label-period, up to 10 further doses of QL1206 could be delivered at the discretion of investigators. Of note, this was done to test the long-term efficacy of use and feasibility of switching from reference denosumab to QL1206.1

The primary outcome of interest for the trial was the percentage change in uNTX/uCR from baseline to week 12. Investigators pointed out the equivalence margins were ±0.135. Secondary outcomes of interest included percentage change in uNTX/uCr from baseline to week 25 and 53, the percentage change in serum bone-specific alkaline phosphatase (s-BALP) from baseline to weeks 13, 25, and 53, and the time to first on-study skeletal-related event.1

Overall, a total of 717 patients were enrolled and underwent randomization between September 2019-January 2021. Of these, 357 were randomized to QL1206 and 360 were randomized to reference denosumab. At baseline, the QL1206 group had a mean age of 56.4±9.9 years, 63.9% were female, mean uNTX/uCR was 78.2±95.8, and 75.9% had an ECOG performance status of 1. In the reference denosumab group, the mean age was 56.8±10.8 years, 69.7% were female, the mean uNTX/uCr was 78.6±87.6 nmoL/mmoL, and 70.6% had an ECOG performance status of 1.1

Upon analysis, results suggested the median percentage changes for the primary endpoint were -75.2% and -75.8% for the QL1206 and reference denosumab groups, respectively, with further analysis pointing to a least-squares mean difference in natural log-transformed ratio of uNTX/uCr at week 12 to baseline between the groups was 0.012 (90% confidence interval, -0.078 to 0.103) within equivalence margins. Analysis of secondary outcomes of interest indicates there were no difference between the groups (P for all>.05). Additionally, results of the safety analyses suggested adverse event rates, immunogenicity, and pharmacokinetics were similar in both groups.1

“QL1206, the first denosumab biosimilar, had a clinical efficacy and safety profile comparable to denosumab. This was also the first study using the surrogate endpoint uNTX/uCr as the primary endpoint to evaluate the efficacy of a denosumab biosimilar,” investigators wrote.1


  1. Li H, Huang Y, Chen Z, et al. Efficacy and Safety of Denosumab Biosimilar QL1206 Versus Denosumab in Patients with Bone Metastases from Solid Tumors: A Randomized Phase III Trial. BioDrugs. 2023;37(2):259-269. doi:10.1007/s40259-023-00579-5
  2. Soloman N. Biosimilars in rheumatology in 2023. HCP Live. December 9, 2022. Accessed May 10, 2023.
  3. Walter K. The use of biosimilars in gastroenterology. HCP Live. April 18, 2023. Accessed May 10, 2023.
  4. Kaiser P. Overview of biosimilars. HCP Live. July 29, 2022. Accessed May 10, 2023.
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