Establishing analytical and clinical similarity between HD201 and herceptin.

Abstract

579 Background: Trastuzumab, an approved prescription drug by EMA and FDA under the name Herceptin has become the key treatment in patients with HER2−positive breast cancer. HD201, developed by Prestige Biopharma Pte Ltd is a biosimilar candidate to Herceptin. The biosimilarity of HD201 was established based on systematic stepwise comparisons between HD201 and reference product, Herceptin. In order to confirm clinical similarity of HD201 to Trastuzumab, two clinical studies were undertaken. Methods: First, in a double-blind, randomised and parallel group study, 101 randomised healthy human subjects were subjected to a single 6 mg/kg IV dose by body weight over 90-min infusion of either HD201, EU- and US-Herceptin group by assessing pharmacokinetic (PK) and safety (TROIKA-I). The second study was a randomised, double-blind, parallel group, equivalence, multicentre clinical phase III trial (TROIKA) designed to compare the efficacy based on total pathological complete response rate (tpCR), safety, and pharmacokinetics of HD201 to EU-Herceptin in patients with HER2 positive early breast cancer. Each group of ~250 subjects were administered with either HD201 or EU-Herceptin in combination with chemotherapy in neoadjuvant followed by the antibody alone in the adjuvant phase. Results: TROIKA-I study demonstrated that HD201 was safe and well tolerated with comparable PK as EU- and US-Herceptin. Based on the neoadjuvant data from TROIKA study, the tpCR rate in the HD201 and Herceptin treatment groups was comparable and the 95% CI was included within the pre-defined margins of equivalence (Table). The incidence and severity of reported TEAEs did not imply any significant safety concerns and were comparable between both groups. In addition, the comparison of steady-state Ctrough between both arms in TROIKA study has established equivalence. Conclusions: The overall comparison exercise demonstrated the equivalence of HD201 to Herceptin. Clinical trial information: 2016-0040019-11 . [Table: see text]

Characteristics of Clinical Trials Evaluating Biosimilars in the Treatment of Cancer

“…After applying our exclusion criteria, we identified 42 studies, and 11 were excluded after final review, leaving 31 studies involving 12 310 patients for detailed analysis (Figure 1; eTable 1 in the Supplement). Twenty-one studies presented an overall low risk of bias, 2 had a high risk of bias, and for 2 trials, the risk of bias was unclear (eTable 2 in the Supplement). All trials were preregistered.…”

“…All but 5 were double-blinded. Eleven studies compared brand-name bevacizumab with a biosimilar, 9 compared brand-name trastuzumab with a biosimilar, and 11 compared brand-name rituximab with a biosimilar …”

“…Nine studies compared the originator trastuzumab and a biosimilar trastuzumab: 4 studies among patients with ERBB2-positive metastatic breast cancer and 5 studies among patients with ERBB2-positive early breast cancer . All trials reported the ORR as their primary end point, and all but 2 early breast cancer trials used the total pathological complete response rate as their primary end point.…”

Safety and efficacy comparisons of intravenous trastuzumab biosimilars to the reference product medicine in treatment‐naïve and switch‐over patients with breast cancer: a systematic and meta‐analysis

“…Overall, nine brands of trastuzumab (BCD-022, ABP980, SB3, CT-P6, PF-05280014, HD201, TrastuRel, MYL-1401O, HLX02) were examined (Table 1). All studies on trastuzumab were conducted with either paclitaxel [11][12][13][14][21][22][23][24][25][26][27][28][29][30] or docetaxel (with 5 fluorouracil epirubicin cyclophosphamide (FEC) [31][32][33][34][35][36][37][38][39][40][41][42][43][44][45] or carboplatin, 46,47 or as monotherapy [15][16][17]48,49 ) or 'taxane' [50][51][52][53][54] (Table 2). One study, by Apsangikar et al, was conducted independently, 21 while all other studies were funded by the innovator company or by an unknown source.…”

“…Forty-one studies reporting on RCTs were identified and included in the analysis, with 34 studies reporting efficacy outcomes (Table 1). Among all included studies, seven reported on ABP 980, 12,[22][23][24][28][29][30] two on BCD-022, 11,27 seven on CT-P6, [31][32][33][34][43][44][45] two on HD201, 14,50 five on HLX02, [15][16][17]48,49 four on MYL-1401O, [51][52][53][54] five on PF-05280014, 13,25,26,46,47 eight on SB3, [35][36][37][38][39][40][41][42] and one on Trasturel. 21 All studies contained data in treatment-na€ ıve patients, and seven studies 12,[22][23][24][28][29]…”