A Phase 1, Double-Blind, Randomised, Parallel Group Study to Demonstrate the Equivalent Pharmacokinetic Properties of a Single Intravenous Dose of HD201 and Herceptin in Healthy Male Subjects

Start Date29 Apr 2019

Sponsor / Collaborator-

NCT03776240 / CompletedPhase 1

A Phase I, Double-Blind, Randomised, Parallel Group Study to Demonstrate the Equivalent Pharmacokinetic Properties of a Single Intravenous Dose of HD201 and EU-Herceptin® and US-Herceptin® in Healthy Male Subjects

The purpose of the study is to demonstrate demonstrate the pharmacokinetic (PK) similarity of HD201 to the European (EU) and American (US) reference products Herceptin, following a single i.v. infusion of 6 mg/kg in healthy volunteers.

Start Date01 Apr 2019

Sponsor / Collaborator

Prestige BioPharma Ltd.

EUCTR2016-004019-11-PL / Not yet recruitingPhase 3

A randomised, double-blind, parallel group, equivalence, multicentre phase III trial to compare the efficacy, safety and pharmacokinetics of HD201 to Herceptin® in patients with HER2+ early breast cancer - Troika

Start Date05 Jun 2018

Sponsor / Collaborator

Prestige BioPharma Ltd.

100 Clinical Results associated with Trastuzumab biosimilar(Hanwha Biologics)

100 Translational Medicine associated with Trastuzumab biosimilar(Hanwha Biologics)

100 Patents (Medical) associated with Trastuzumab biosimilar(Hanwha Biologics)

Literatures (Medical) associated with Trastuzumab biosimilar(Hanwha Biologics)

01 May 2022·JAMA oncologyQ1 · MEDICINE

Efficacy of HD201 vs Referent Trastuzumab in Patients With ERBB2-Positive Breast Cancer Treated in the Neoadjuvant Setting

Q1 · MEDICINE

Article

Author: Soo Hoo, Hwoei Fen ; Petrelli, Fausto ; Georgievich, M. A. ; Kim, Jamie ; Jaison, Litha ; Kaewkangsadan, Viriya ; Dzagnidze, Giorgi ; Nikolaevich, Lipatov O. ; Deforce, Filip ; Cox, David G. ; Derde, Marie-Paule ; Shamrai, Volodymyr ; Kaufman, Leonard ; Villanueva, Cristian ; Pivot, Xavier ; Bonamy, Ghislain M. C. ; Hii, Jocelyn ; Pradhan, Sumita ; Feyaerts, Peggy

Importance:

The drug HD201 is a biosimilar candidate for breast cancer treatment as the reference trastuzumab.

Objective:

To compare the efficacy of HD201 with referent trastuzumab.

Design, Setting, and Participants:

This randomized clinical trial (TROIKA) included 502 women with ERBB2-positive early breast cancer treated with either HD201 or referent trastuzumab. It was conducted across 70 centers in 12 countries, including Western and Eastern Europe and Asian countries. Randomization was stratified by tumor hormone receptor status, clinical stage, and geographic region of recruitment. This analysis was conducted on February 12, 2021, after the completion of the adjuvant phase at a median of 31 months (IQR, 28-33 months) of follow-up.

Interventions:

Patients with ERBB2-positive early breast cancer were randomly assigned to receive HD201 or referent trastuzumab in the neoadjuvant setting for 8 cycles, concurrently with 4 cycles of docetaxel, which was followed by 4 cycles of epirubicin and cyclophosphamide. Patients then underwent surgery, which was followed by treatment with 10 cycles of adjuvant HD201 or referent trastuzumab.

Main Outcome and Measures:

The primary end point was the total pathological complete response (tpCR) assessed after neoadjuvant treatment. Equivalence was concluded if the 95% CI of the absolute difference in tpCR between arms in the per-protocol set was within the margin of more or less than 15%. Other objectives included the breast pathological complete response, overall response, event-free and overall survival, safety, pharmacokinetics, and immunogenicity.

Results:

A total of 502 female patients (mean [range] age, 53 [26-82] years) were randomized to receive either HD201 or referent trastuzumab, and 474 (94.2%) were eligible for inclusion in the per-protocol set. The baseline characteristics were well balanced between the 2 arms; 195 tumors (38.8%) were hormone receptor-negative , and 213 patients (42.4%) had clinical stage III disease. The tpCR rates were 45% and 48.7% for HD201 and referent trastuzumab, respectively. The difference between the 2 groups was not significant at -3.8% (95% CI, -12.8% to 5.4%) and fell within the predefined equivalence margins. The ratio of the tpCR rates between the 2 arms was 0.92 (95% CI, 0.76 to 1.12). A total of 433 patients (86.1%) presented with 2232 treatment-emergent adverse events of special interest for trastuzumab during the entire treatment period, with 220 (88.0%) and 213 (84.5%) patients in the HD201 and referent trastuzumab groups, respectively.

Conclusions and Relevance:

The results of this randomized clinical trial found that HD201 demonstrated equivalence to referent trastuzumab in terms of efficacy for the end point of tpCR, with a similar safety profile.

Trial Registration:

ClinicalTrials.gov Identifier: NCT03013504.

01 Aug 2021·Pharmacology research & perspectivesQ4 · MEDICINE

TROIKA‐1: A double‐blind, randomized, parallel group, study aimed to demonstrate the equivalent pharmacokinetic profile of HD201, a potential biosimilar candidate to trastuzumab, versus EU‐Herceptin^® and US‐Herceptin^® in healthy male subjects

Q4 · MEDICINE

ArticleOA

Author: Derde, Marie Paule ; Feyaerts, Peggy ; Mclendon, Kristi ; Deforce, Filip ; Ang, Felicia ; Pivot, Xavier ; Jaison, Litha ; Chung Shii Hii, Jocelyn ; Detappe, Alexandre ; Park, Lisa Soyeon ; Demarchi, Martin ; Kim, Michael Jinwoo ; Coliat, Pierre

Abstract:

Prestige Biopharma Ltd (Singapore) has developed HD201, a proposed biosimilar to reference product trastuzumab. As a part of the stepwise approach to ensure comparability between the biosimilar candidate and the reference medicinal product, a phase I study in healthy subjects was conducted to demonstrate the pharmacokinetic (PK) equivalence (NCT03776240). The primary objective of the study was to demonstrate (PK) equivalence of HD201, EU‐Herceptin®, and US‐Herceptin® given at 6 mg/kg as a 90‐min i.v. infusion to healthy male subjects. A pairwise comparisons based on the primary endpoint AUC0–inf and secondary PK endpoints, AUC0–last and Cmax were undertaken. PK equivalence was to be concluded if the 90% confidence interval (CI) for the ratio of geometric means for each criterion were within the equivalence margin of 80% to 125%. Secondary objectives included assessment of other PK parameters, safety, tolerability, and immunogenicity in the three arms. A total of 105 healthy male subjects (35/treatment) were randomized in this study. The 90% CI for the ratios of AUC0–inf, Cmax and AUC0–last, were within 80%–125% for the comparisons of HD201 to EU‐Herceptin® or US‐Herceptin® and EU‐Herceptin® to US‐Herceptin®. The frequency of subjects with TEAEs of special interest was slightly lower in the HD201 group (20.0%) compared to the other treatment groups (EU‐Herceptin®: 34.3%; US‐Herceptin®: 31.4%). Only 1 subject (EU‐Herceptin® group) developed anti‐drug antibodies prior to dosing. Overall, HD201 demonstrates PK similarity to both EU‐Herceptin® and US‐Herceptin®. The three study drugs also demonstrated similar safety profiles.

01 Mar 2018·Clinical therapeuticsQ4 · MEDICINE

A Randomized Phase I Study Comparing the Pharmacokinetics of HD201, a Trastuzumab Biosimilar, With European Union–sourced Herceptin

Q4 · MEDICINE

Article

Author: Pivot, Xavier ; Park, Lisa Soyeon ; Deslypere, Jean Paul ; Kim, Michael Jinwoo ; Lee, Wonjae ; Lee, Jeonghyeon

PURPOSE:

This first-in-human study of HD201 was designed to evaluate the pharmacokinetic (PK) equivalence between this biosimilar candidate and trastuzumab sourced in the European Union (EU-trastuzumab)*.

METHODS:

In this randomized, blinded, single-dose comparative PK study, healthy male subjects were randomized to receive a single 6 mg/kg IV dose of HD201 or EU-trastuzumab. The primary PK end point was AUC_0-∞. Equivalence was determined by using the predefined margins of 0.8 to 1.25. Other PK parameters were included as secondary end points.

FINDINGS:

Baseline demographic characteristics for the 73 randomized subjects were similar across the 2 groups: median age 29 and 30 years old (ranges 19 - 45), median weight 78.6 and 81.7 kg (ranges 60.2 - 101). The 90% CIs for the geometric least squares mean of the AUC_0-∞ were included within the margins of 0.8 to 1.25. All other PK parameters were comparable for both HD201 and EU-trastuzumab. The proportions of subjects who experienced adverse events related to the study drug were 61.8% and 82.9% in the HD201 and EU-trastuzumab groups, respectively. The most frequently reported adverse events related to the study drug were infusion-related reactions. No subjects had positive results for antidrug antibodies after a single dose.

IMPLICATIONS:

This study reported the PK equivalence between HD201 and EU-trastuzumab. HD201 was well tolerated with no safety concerns after single-dose administration in healthy male subjects. EudraCT No.: 2012-000805-56.

News (Medical) associated with Trastuzumab biosimilar(Hanwha Biologics)

14 Oct 2022

·www.biospace.com

FDA Review: Phanes, Pfizer, GSK and More

The FDA has numerous activities and interactions with Phanes, Prestige Biopharma, Reata, Pfizer and more, providing clearance, approving clinical trials and other regulatory actions. Here’s a look at what kept the agency busy this week. Oct. 14 Phanes Therapeutics was cleared to initiate a Phase I trial of PT217, an anti-Delta-like ligand 3 (DLL3)/anti-Cluster of differentiation 47 (CD47) bispecific antibody for small cell lung cancer and other neuroendocrine cancers. Prestige Biopharma submitted a request to the FDA for a pre-submission meeting to discuss its expected BLA application for a Herceptin biosimilar, HD201(Tuznue). Oct. 13 Reata Pharmaceuticals announced the FDA informed the company it will not hold an advisory committee meeting related to its New Drug Application (NDA) for omaveloxolone for treatment of Friedreich’s ataxia. Oct. 12 Eagle Pharmaceuticals submitted an Investigational New Drug (IND) application for a Phase II trial of CAL-02 for treatment of severe community-acquired bacterial pneumonia. Galactin Therapeutics received the go-ahead for a Phase II trial of belapectin with Merck’s Keytruda (pembrolizumab) for first-line treatment of recurrent/metastatic PD-L1 positive squamous cell carcinoma of the head and neck. Regeneron Pharmaceuticals reported the FDA accepted for Priority Review its supplemental Biologics License Application (sBLA) for Eylea (aflibercept) injection to treat Retinopathy of Prematurity (ROP) in preterm infants. Pfizer and BioNTech received Emergency Use Authorization (EUA) for a 10-microgram dose of their Omicron BA.4/BA.5 bivalent COVID-19 vaccine for kids 5 through 11 years of age. SiSaf initiated the FDA regulatory process to obtain Orphan Drug Designation for SIS-101-ADO, a siRNA therapeutic for Autosomal Dominant Osteopetrosis Type 2 (ADO2). BridgeBio Pharma announced the FDA granted Fast Track designation for BBP-398 in combination with Amgen’s Lumakras (sotorasib) for adults with previously treated KRAS G12C-mutated, metastatic non-small cell lung cancer. Oct. 11 Eligo Bioscience’s EB003 received Orphan Drug Designation and Rare Pediatric Disease designation for EB003 to treat Shiga-toxin producing bacterial infection as it relates to the prevention of hemolytic uremic syndrome. Incannex Healthcare reported it completed a constructive pre-IND meeting with the FDA for its IHL-216A for treatment of traumatic brain injury and concussion. Aquestive Therapeutics received positive written feedback from the FDA for its initial End-of-Phase II meeting request to discuss Chemistry, Manufacturing and Controls (CMC) for its AQST-109 epinephrine sublingual film for the treatment of severe allergic reactions, including anaphylaxis. XACT Robotics’ ACE Xtend Remote Control Unit was granted FDA clearance, allowing users to robotically insert and steer the XACT ACE Robotic System remotely from a control room. Biomind Labs announced the FDA granted a Pre-IND meeting for its Triptax, a new chemical entity that could be used as an active pharmaceutical ingredient or chemical precursor to treat depression. Gilead Sciences reported the FDA accepted an sBLA for Trodelvy (sacituzumab govitecan-hziy) for priority review for the treatment of adults with unresectable locally advanced or metastatic HR+/HER- breast cancer who have received endocrine-based therapy and at least two additional systemic therapies in the metastatic setting. TeraImmune received the go-ahead to initiate a Phase I/IIa trial of TI-168 in congenital Hemophilia A patients with refractory inhibitors. TI-168 is a next-generation, autologous FVIII TCR-Treg cell therapy. Oct. 10 scPharmaceuticals’ Furoscix (furosemide injection) was approved for the treatment of congestion due to fluid overload in adults with New York Heart Association Class II/III chronic heart failure. The FDA issued its briefing documents arguing for the market withdrawal of Covis Pharma’s Makena, which was approved to reduce the risk of preterm birth in women with a singleton pregnancy with a history of spontaneous preterm birth. IRadimed Corporation voluntarily withdrew its 510(k) application for its next-generation MR IV pump due to the need to supply additional information within a timeline the company could not manage. Nanoscope Therapeutics received Fast Track Designation for MCO-0101, an ambient-light activatable Multi-Characteristic Opsinoptogenetic monotherapy to restore vision in blind patients for the treatment of retinitis pigmentosa by way of intravitreal injection. Oct. 7 GlaxoSmithKline’s Boostrix, a vaccine against whooping cough, was approved by the FDA for infants under the age of two months.

AntibodyOrphan DrugBiosimilarCell TherapyVaccine

11 Mar 2022

·www.biospace.com

Biosimilar development continues to advance for the U.S. market in anticipation of becoming an alternative to a brand drug with similar safety and efficacy. Earlier this month, Kashiv BioSciences won FDA approval for Releuko, a biosimilar to Amgen’s Neupogen. Releuko, which was co-developed with Amneal Pharmaceuticals, is expected to launch in the third quarter of 2022 as a treatment for neutropenia, a low white blood cell condition experienced by chemotherapy patients. Two other biosimilars for Neupogen have been approved, including Zarxio and Nivestym. Chandramauli Rawal, chief operating officer for Kashiv, said the company is one of the few U.S. –based companies to manufacture and launch a biosimilar for the U.S. market. Beyond the Neupogen biosimilar, Rawal said Kashiv is also developing a biosimilar to Amgen’s Neulasta. It aims for approval of its Biologics License Application later this year. Additionally, Kashiv and Amneal hope to secure approval for a biosimilar to Genentech’s Avastin. Chirag and Chintu Patel, co-chief executive officers for Amneal, noted that biosimilars represent the “next wave of providing access to affordable medicines in the U.S.” They said Amneal intends to become a long-term player in the biosimilar market. Biosimilars are biologic products that are highly similar to a branded drug but are always uniquely different in composition. Biosimilar treatments can be attractive to treating physicians because of the understanding that the products are so similar to the original reference drug. That makes them equally as effective and available at a significant cost reduction. Since Zarxio was first approved in 2015 by the FDA, there have been 33 other biosimilars that have received the green light in the U.S. Not all of them are yet on the market due to existing patents that protect against the competition, such as the case with AbbVie’s Humira. Patent protection for that drug, which generated about $20 billion in revenue in 2021, fall next year, paving the way for multiple biosimilars. Multiple companies have been making headway with biosimilars in the U.S., even as some have fought tooth and nail to prevent competition for their branded drugs. Biosimilar treatments have a stronger platform in Europe, which has been in use for years. However, in the U.S., traction has been somewhat difficult due to some systemic issues with insurance programs, including formulary design and overcoming some misinformation regarding safety and efficacy, a recent report showed. The report, Improving Drug Management: Employer Strategies on Biosimilars, was authored by the National Alliance of Healthcare Purchaser Coalitions. “The U.S. lags Europe in embracing and expanding the biosimilars market,” Michael Thompson, National Alliance president and CEO, said in a statement. “Educating plan sponsors about barriers to broader adoption of biosimilars will enable them to challenge the market dynamics blocking this critical channel to achieve a more competitive drug market.” Prestige BioPharma, a Singapore-based company, hopes to break through those market barriers with its Herceptin biosimilar. This morning, the company announced positive Phase III results that show HD201 has a comparative safety and efficacy to the Genentech cancer drug. Data was published in the Journal of the American Medical Association Oncology. If approved, HD201 will be marketed under the brand name Tuznue. Prestige said the difference between the Herceptin treatment group and the HD201 group was not significant and fell within the predefined equivalence margins. Similar safety, P.K. and immunogenicity results were reported for the two treatment arms. Some analyses are ongoing, including three-year event-free survival, as well as overall survival. The preliminary results of the current final analysis indicate highly comparable rates in both areas for HD201 and Herceptin. In addition to the Herceptin biosimilar, Prestige is also developing an Avastin biosimilar and a Humira biosimilar.

Filgrastim biosimilar(KASHIV BIOSCIENCES LLC)Kashiv Biosciences LLCBiosimilarNeutropeniaAntibodyLicense out/in

11 Mar 2022

·www.biospace.com

The Result of the Phase 3 Study for Prestige BioPharma’s Herceptin Biosimilar, HD201(Tuznue®), Published in JAMA Oncology

Prestige BioPharma Limited (950210: KRX), a Singapore-based biopharmaceutical with operations in USA and South Korea, announced positive efficacy and safety results of the Phase 3 study for HD201 (TROIKA), a biosimilar to Herceptin® (trastuzumab), published in JAMA Oncology on March 4, 2022. The publication highlights comparative efficacy and safety data for patients who received 1-year of treatment with HD201 or referent trastuzumab and completed a median follow-up of 31 months. The study met its primary endpoint (tpCR) and showed equivalent efficacy and comparable safety profile. The tpCR rates were 45% and 48.7% for HD201 and referent trastuzumab, respectively. The difference between the two groups was not significant at −3.8% (95% CI, −12.8% to 5.4%) and fell within the predefined equivalence margins. The results regarding secondary endpoints bpCR, overall response, and response based on mammography, ultrasonography, or clinical tumor evaluations supported the comparable efficacy between HD201 and referent trastuzumab. Similar safety, PK and immunogenicity results were reported for the two treatment arms. The final analysis for the 3-year Event-free survival (EFS) and Overall survival (OS) results is currently ongoing. The preliminary results of the current final analysis indicate highly comparable 3-year EFS and OS rates for HD201 and reference trastuzumab. Tuznue® has secured global distribution partnerships in major markets including Europe, the Middle East, South America, and Asia. It is currently under Marketing Authorization Application (MAA) review in EU EMA, Canada and South Korea. Prestige’s robust pipeline in clinical stage also includes an Avastin biosimilar HD204 (Vasforda®) in global Phase 3, and a Humira biosimilar PBP1502 in Phase 1 clinical trial in Europe. Lisa S. Park, CEO of Prestige BioPharma, commented: “We are pleased to demonstrate HD201’s excellence through the Phase 3 study results published in JAMA Oncology” and “the company will accelerate global launch of Tuznue that can enhance affordability of trastuzumab to the patients in need”.

Trastuzumab biosimilar(Hanwha Biologics)Biosimilar

100 Deals associated with Trastuzumab biosimilar(Hanwha Biologics)

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
HER2 Positive Breast Cancer	NDA/BLA	EU	Prestige BioPharma Ltd.	-
Stomach Cancer	NDA/BLA	EU	Prestige BioPharma Ltd.	-

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03013504 (TROIKA, Pubmed)	Phase 3	HER2 Positive Breast Cancer Neoadjuvant	502	HD201	hpfsmquqbc(tcfdmmygud) = During the posttreatment follow-up period, adverse events were reported for 64 (27.4%) and 72 (29.8%) patients in the HD201 and the reference trastuzumab groups, respectively olgdnllamr (kzhoifmuro ) View more	Positive	31 Jan 2023
				Referent trastuzumab
NCT03013504 (TROIKA, ESMO_ASIA2022) Manual	Phase 3	HER2 Positive Breast Cancer Neoadjuvant ERBB2-positive	474	HD201 6 mg/kg/8 mg/kg+docetaxel+epirubicin+cyclophosphamide	gfqrludkot(bfmwymarjz) = grktkwngjc pqknolrcgh (udmiisysgq ) View more	Similar	03 Dec 2022
				Trastuzumab 6 mg/kg/8 mg/kg+docetaxel+epirubicin+cyclophosphamide	gfqrludkot(bfmwymarjz) = psprfsfood pqknolrcgh (udmiisysgq ) View more
NCT03013504 (TROIKA, Pubmed \| JAMA Oncol) Manual	Phase 3	HER2 Positive Breast Cancer Neoadjuvant ERBB2 Positive	502	docetaxel+epirubicin+cyclophosphamide+HD201	eetfsuvhhh(dutmkvaddy) = ituzdiumpi cqlcodxwcp (tqefbpvvgo ) View more	Similar	03 Mar 2022
				docetaxel+epirubicin+cyclophosphamide+Trastuzumab	eetfsuvhhh(dutmkvaddy) = yzgkblyezs cqlcodxwcp (tqefbpvvgo ) View more
NCT03776240 (TROIKA-1, Pubmed) Manual	Phase 1	-	105	HD201	wzguwswioj(hwsxmanipw) = were within 80%-125% for the comparisons of HD201 to EU-Herceptin or US-Herceptin and EU-Herceptin to US-Herceptin uaxuhypkhh (tkktfuanxp )	Positive	01 Aug 2021
				Herceptin
EUCTR2016-004019-11-ES (TROIKA, ESMO2020) Manual	Phase 3	HER2 Positive Breast Cancer Neoadjuvant HER2 Positive	503	HD201+chemotherapy	asuaromphw(vlpycdezdy) = msfcfpqpgq chwjfuraqw (vhrgegmbfa ) View more	Similar	18 Sep 2020
				Herceptin+chemotherapy	asuaromphw(vlpycdezdy) = ubqteofrpo chwjfuraqw (vhrgegmbfa ) View more

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