Hanlikang (rituximab biosimilar) / Fosun Pharma, Eurofarma, Farma de Colombia, Abbott - LARVOL DELTA

Palleon Pharmaceuticals and Henlius Collaborate to Advance Glycan Editing as a Treatment for Autoimmune Diseases (Businesswire) - "Palleon Pharmaceuticals...today announced a collaboration and license agreement with Shanghai Henlius Biotech, Inc. (2696.HK) to develop and commercialize Palleon’s first-in-class human sialidase enzyme therapeutic, E-602, in combination with Henlius’ self-developed HANLIKANG (rituximab) in patients with autoimmune diseases, including lupus nephritis (LN)....Under the terms of the agreement, Henlius received an exclusive China license to Palleon’s E-602. Palleon is eligible to receive up to $95.3 million in certain predetermined development and commercial milestones, in addition to royalties upon E-602 commercialization in China."

Licensing / partnership • Immunology • Lupus Nephritis

Henlius Maintains Patient-Centric Focus, Drives Sustainable Growth, and Accelerates Overseas Expansion in 2024 H1 (Henlius Press Release) - "In the first half of 2024, HANLIKANG, the first biosimilar launched in China...The company also plans to submit marketing applications for...HLX11 (pertuzumab biosimilar) in China and the U.S. in the second half of 2024."

China filing • FDA filing • Launch non-US • Oncology

Henlius Maintains Patient-Centric Focus, Drives Sustainable Growth, and Accelerates Overseas Expansion in 2024 H1 (Henlius Press Release) - "HANQUYOU (trastuzumab, trade name: HERCESSI in the U.S., Zercepac in Europe), HANSIZHUANG (serplulimab), and HANBEITAI (bevacizumab) recorded sales of RMB1.4743 billion, RMB677.8 million and RMB86.7 million, respectively. In addition, the company received sales revenues of RMB227.0 million and RMB13.6 million based on the collaboration with partners for HANLIKANG (rituximab)..."

Sales • Colorectal Cancer • Esophageal Cancer • Follicular Lymphoma • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • HER2 Positive Breast Cancer • Lung Non-Small Cell Squamous Cancer • Neuroendocrine Tumor • Small Cell Lung Cancer

Henlius Rituximab Receives Marketing Approval in Peru (Henlius Press Release) - "Recently, HANLIKANG (rituximab), independently developed and manufactured by Henlius, has been approved to be marketed in Peru under the trade name AUDEXA by the Dirección General de Medicamentos, Insumos y Drogas (DIGEMID). HANLIKANG is the third product that has been developed and manufactured by Henlius independently and approved for overseas marketing....The approval of HANLIKANG by DIGEMID in Peru is mainly based on the review of a series of data. The application dossier is mainly based on the information submitted to China’s National Medical Products Administration (NMPA) in the New Drug Application (NDA)."

Approval • Chronic Lymphocytic Leukemia • Non-Hodgkin’s Lymphoma • Rheumatoid Arthritis

Henlius to Showcase at BIO 2024 (Henlius Press Release) - "From June 3-6, 2024, the 2024 Biotechnology Innovation Organization International Convention...will be held in San Diego Convention Center, California, USA....During BIO 2024, the company will be at Booth #1719 with 5 launched products, including HANLIKANG (rituximab), the first China-developed biosimilar, HANQUYOU (trastuzumab for injection, trade name: HERCESSI in the U.S and Zercepac in Europe) and its innovative product HANSIZHUANG, the world’s first anti-PD-1 mAb for the first-line treatment of small cell lung cancer."

Clinical • Breast Cancer • Chronic Lymphocytic Leukemia • Hematological Malignancies • HER2 Breast Cancer • HER2 Positive Breast Cancer • Lung Cancer • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Small Cell Lung Cancer • Solid Tumor

Long-term outcomes with HLX01 (HanliKang), a rituximab biosimilar, in previously untreated patients with diffuse large B-cell lymphoma: 5-year follow-up results of the phase 3 HLX01-NHL03 study. (PubMed, BMC Cancer) - "Patients were randomised to either rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) or HLX01 plus CHOP (H-CHOP) every 21 days for up to six cycles. Treatment outcomes did not differ between groups regardless of IPI score and were consistent with the primary analysis. H-CHOP and R-CHOP provided no significant difference in 5-year OS or PFS in previously untreated patients with low or low-intermediate risk DLBCL."

Journal • P3 data • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD20

Novel Chemotherapy-Free Initial Treatment of Rituximab Biosimilar Plus Pegylated Interferon α-2b in Pts with Untreated Advanced Indolent B-Cell Non-Hodgkin's Lymphoma: Results of the Ripple 3-Year Follow-up Study (ASH 2023) - P2 | "During induction phase, pts received rituximab biosimilar (Henliritux® Shanghai Henlius Biotech) 375 mg/m2 intravenous infusion on d1. Peg-IFN-α2b (Pegberon®, Xiamen Amoytop Biotech) was given at a dose of 135ug, subcutaneously, on d1,8...Simultaneously, CHB pts orally treated with entecavir continuously... Rituximab biosimilar plus pegylated interferon α-2b provided favorable response in newly diagnosed advanced iBCL with mild toxicity. No hepatitis B virus reactivation was observed."

Clinical • Metastases • Anemia • Fatigue • Follicular Lymphoma • Hematological Malignancies • Hepatitis B • Hepatology • Indolent Lymphoma • Infectious Disease • Lymphoma • Lymphoplasmacytic Lymphoma • Marginal Zone Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Small Lymphocytic Lymphoma • Thrombocytopenia • Waldenstrom Macroglobulinemia • IFNA1

Henlius Xuhui Facility Passes Colombian GMP Inspection for HANLIKANG (Henlius Press Release) - "Shanghai Henlius Biotech...announces that recently, it has received the resolution of the Colombian National Food and Drug Surveillance Institute (the 'INVIMA') to grant it the GMP certification, pursuant to which the company’s manufacturing site Xuhui Facility has successfully passed the GMP inspection by the INVIMA for the related production lines of HANLIKANG and meets Colombian GMP standards. INVIMA certifies quality management system by adopting WHO standards and wins high recognition in South America. The GMP certification by Colombia, along with the GMP certification by Brazil, brings HANLIKANG a step further to South American countries."

Commercial • Chronic Lymphocytic Leukemia • Non-Hodgkin’s Lymphoma

Henlius Xuhui Facility Passes PIC/S Member ANVISA GMP Inspection for HANLIKANG and HANQUYOU (Henlius Press Release) - "Shanghai Henlius Biotech, Inc...announces that recently, it has received GMP certificates issued by the Brazilian National Health Surveillance Agency (Portuguese: Agência Nacional de Vigilância Sanitária,'ANVISA'), one of the Pharmaceutical Inspection Co-operation Scheme (PIC/S) participating members, indicating that its Xuhui Facility passes the GMP inspection of the drug substance (DS) and drug product (DP) production lines of its rituximab HANLIKANG and trastuzumab HANQUYOU (trade name in Europe: Zercepac^®; trade names in Australia: Tuzucip^® and Trastucip^®) by ANVISA and meets PIC/S GMP standards. This is the first time that the production lines of HANLIKANG have passed GMP inspection conducted by an overseas authority."

Non-US regulatory • Breast Cancer • Chronic Lymphocytic Leukemia • Gastric Cancer • Gastrointestinal Cancer • Hematological Malignancies • HER2 Breast Cancer • HER2 Positive Breast Cancer • Immunology • Inflammation • Inflammatory Arthritis • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Rheumatoid Arthritis • Solid Tumor

Henlius 2023 H1 Results: Achieved record profits and RMB2.5 billion revenues, opening a new chapter of high-quality growth (PRNewswire) - "In the first half of 2023, Henlius achieved a total sales revenue at a record high of approximately RMB2.1529 billion increased by 82.2% YoY, with its ever-increasing self-supporting capability, driving the company into a new stage of sustainable development. The company has established a professional and efficient commercial team to build a business presence in the China market and drive the market penetration on the in-house products HANQUYOU, HANSIZHUANG and HANBEITAI (bevacizumab). In the first half of 2023, these core products of the company gained sales revenue of RMB1.2767 billion, RMB556.3 million and RMB44.9 million, respectively. In addition, the company received a profit-sharing of RMB254.1 million and RMB20.8 million for HANLIKANG (rituximab)..."

Commercial • Sales • Breast Cancer • Colorectal Cancer • Gastric Cancer • Gastrointestinal Cancer • Head and Neck Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck

Disease Characteristics and Treatment Outcomes with HLX01: A Real-World Study in Patients with B-Cell Non-Hodgkin Lymphoma in China (ASH 2022) - "Rituximab (R) has changed the treatment landscape of NHL; approvals of rituximab biosimilars have improved access to and the affordability of this treatment (Mohammed et al., J Blood Med 2019).HLX01 is the first rituximab biosimilar approved for the treatment of NHL and chronic lymphocytic leukemia in China. The most common AEs were decreased white blood cell count (3.9%), decreased neutrophil count (3.5%), and nausea/vomiting (3.3%).Conclusion s DLBCL is the most common subtype in HLX01-treated patients with B-cell NHL in China. HLX01 showed clinical benefits with favorable safety profiles in patients with B-cell NHL subtypes in a real-world setting"

Clinical • Real-world evidence • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Disorders • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Rituximab Biosimilar Combined with Pegylated Interferon α-2b in Patients with Untreated Advanced Indolent B-Cell Non-Hodgkin's Lymphoma: Preliminary Results from a Multicenter, Single-Arm, Phase II Study (ASH 2021) - P2 | "During induction phase, pts received rituximab biosimilar (Henliritux ® Shanghai Henlius Biotech) 375 mg/m 2 intravenous infusion on d1. Peg-IFN-α2b (Pegberon ® , Xiamen Amoytop Biotech) was given at a dose of 135ug, subcutaneously, on d1,8...Simultaneously, CHB pts orally treated with entecavir continuously... Rituximab biosimilar plus pegylated interferon α-2b provided favorable response in newly diagnosed advanced iBCL and was well tolerated. No hepatitis B virus reactivation was observed. Further investigation is warranted."

Clinical • P2 data • Anemia • Fatigue • Hematological Malignancies • Hepatitis B • Hepatology • Indolent Lymphoma • Infectious Disease • Inflammation • Lymphoma • Marginal Zone Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Thrombocytopenia • IFNA1

A Clinical Study of Hanlikang and BTK Inhibitors in the Treatment of Newly Diagnosed Mantle Cell Lymphoma (clinicaltrials.gov) - P=N/A | N=100 | Recruiting | Sponsor: Zhengzhou University

New trial • Hematological Malignancies • Mantle Cell Lymphoma • Oncology • Solid Tumor

Rituximab biosimilar HLX01 versus reference rituximab in the treatment of diffuse large B-cell lymphoma: Real-world clinical experience. (PubMed, J Oncol Pharm Pract) - "HLX01 is a suitable replacement for reference rituximab in the treatment of diffuse large B-cell lymphoma and is relatively inexpensive, thereby reducing the economic burden of patients. Nevertheless, the conclusion of this study still needs to be further validated by large-sample real-world data and explored for HLX01 in other indications, such as follicular lymphoma."

Journal • Real-world evidence • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Efficacy and safety of HLX01 in patients with moderate-to-severe rheumatoid arthritis despite methotrexate therapy: a phase 3 study. (PubMed, Arthritis Res Ther) - P3 | "HLX01 plus methotrexate improved clinical outcomes compared with placebo in Chinese patients with rheumatoid arthritis who had inadequate responses to methotrexate. This treatment regimen was well tolerated, showing comparable safety profiles to placebo."

Journal • P3 data • Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology

RIPPLE: Rituximab and Pegylated Interferon α-2b in Patients With Indolent B-cell Lymphoma (clinicaltrials.gov) - P2 | N=52 | Recruiting | Sponsor: Huiqiang Huang | Trial primary completion date: Jan 2022 ➔ Jun 2022

Combination therapy • Trial primary completion date • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Indolent Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

HLX301 (TIGIT×PDL1 Bispecific) in Patients With Locally Advanced or Metastatic Solid Tumors (clinicaltrials.gov) - P1/2; N=150; Not yet recruiting; Sponsor: Shanghai Henlius Biotech

Clinical • IO biomarker • New P1/2 trial • Gastrointestinal Cancer • Hepatocellular Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck

First China-Manufactured Proposed MabThera® Biosimilar Met Primary Efficacy and Safety Endpoints in CD20-Positive Diffuse Large B-Cell Lymphoma (ESMO Asia 2018) - P3; " Upon successful demonstration of equivalence in safety, PK/PD in previously-treated patients with CD20(+) BCL, we subsequently conducted a multi-center, double-blind, randomized, parallel-control Phase 3 study comparing the primary efficacy in best objective response rate (ORR) and safety profiles for six 3-week cycle treatments of 375mg/m2 either HLX01 with cyclophosphamide, doxorubicin, vincristine and prednisone (H-CHOP) or rituximab CHOP (R-CHOP) in patients with treatment-naïve CD20+ diffuse large B cell lymphoma (DLBCL).Results :A total of 81 CD20(+) BCL patients who have reached complete response (CR) or CR uncertain (CRu) after treatment was randomized to receive a single infusion of 375mg/m2 either HLX01 (n = 40) or rituximab-CN (n = 41). We report successful demonstration of equivalence in, PK/PD, efficacy and safety between HLX01 and rituximab sourced from China. Furthermore, HLX01 does not demonstrate new safety signals in comparison with rituximab."

Clinical • Diffuse Large B Cell Lymphoma

First China Approved Rituximab Biosimilar HLX01: Pharmacokinetics, Safety and Efficacy Comparison to Reference Rituximab in the Phase 3 Diffuse Large B-Cell Lymphoma Study (ASH 2019) - P1/2, P3; "Methods In this multicenter, randomized, double-blind, parallel active-controlled, Phase 3 study (NCT02787239), treatment-naïve adults aged 18-80 years with histologically confirmed CD20+ DLBCL were treated with cyclophosphamide-doxorubicin-vincristine-prednisone (CHOP) and randomly assigned at 1:1 ratio to co-administer with HLX01 (H-CHOP) or RTX (R-CHOP) every 21 days cycle treatment. Based on the totality of evidence with the results from this Phase 3 study and PopPK modeling, China NMPA approved HLX01 as the first China RTX biosimilar with the potential to provide alternative treatment option for patients. To the best of our knowledge, we are the first reporting the establishment of biosimilarity with RTX in DLBCL patient population."

Clinical • P3 data • PK/PD data • Diffuse Large B Cell Lymphoma • Hematological Disorders • Hematological Malignancies • Immunology • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Rheumatoid Arthritis • Rheumatology

A population pharmacokinetic model: Assessment of pharmacokinetic similarity of HLX01 and rituximab in diffuse large B-cell lymphoma (ESMO Asia 2019) - P1/2, P3; "This PopPK model derived from RA patients adequately predicts HLX01 and CN-RTX in patients with CD20+ DLBCL. HLX01 and EU-/CN-RTXs had similar PK parameters and influential PK covariates. These results provided further evidence for PK similarity between HLX01 and RTXs in patients with RA or DLBCL regardless of ethnicity.Legal entity responsible for the study: Shanghai Henlius Biotech, Inc."

Clinical • PK/PD data

A new population model validated pharmacokinetic similarity of HLX01 and rituximab in B-cell lymphoma (ESMO 2019) - P1/2, P3; "This PopPK model derived from RA patients can predict HLX01 and CN-RTX in patients DLBCL. HLX01 and EU-/CN-RTX had similar PK parameters and influential PK covariates. These results provided further evidence for PK similarity between HLX01 and RTXs in patients with RA or DLBCL."

Clinical • PK/PD data

Fosun Pharma Announces 2021 Interim Results - “During the Reporting period, Fosun Pharma's R&D expenditure amounted to RMB1,954 million, representing an increase of 15.69% YOY. In particular, the R&D expenses amounted to RMB1,562 million, representing an increase of 29.73% YOY…During the Reporting Period, the sales volume of self-developed product Han Li Kang (Rituximab Injection) achieved substantial sales growth. In the first half of the year, it contributed revenue of RMB724 million, representing an increase of 223.21% YOY. Han Qu You (Trastuzumab Injection)…”

Commercial • Sales • Oncology

Phase 1 studies comparing safety, tolerability, pharmacokinetics and pharmacodynamics of HLX01 (a rituximab biosimilar) to reference rituximab in Chinese patients with CD20-positive B-cell lymphoma. (PubMed, Chin J Cancer Res) - P1, P1/2 | "Treatment with HLX01 was safe and well tolerated in Chinese patients with B-cell lymphoma. HLX01 and rituximab-CN have similar pharmacokinetic, pharmacodynamic and safety profiles."

Clinical • Journal • P1 data • PK/PD data • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD19 • CD20

[VIRTUAL] EFFICACY AND SAFETY OF HLX01 COMBINED WITH METHOTREXATE IN CHINESE PATIENTS WITH MODERATELY TO SEVERELY ACTIVE RHEUMATOID ARTHRITIS WHO HAD INADEQUATE RESPONSES TO METHOTREXATE: RESULTS OF A RANDOMISED, DOUBLE-BLIND, PLACEBO-CONTROLLED PHASE 3 STUDY (EULAR 2021) - P3 | "Comparing with placebo plus MTX, HLX01 plus MTX showed significantly improved clinical outcomes and comparable safety profiles in Chinese patients with moderately to severely active RA who had inadequate responses to MTX, demonstrating HLX01 in combination with MTX as a well-tolerated, safe and efficient treatment option."

Clinical • P3 data • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Immunology • Infectious Disease • Inflammatory Arthritis • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Respiratory Diseases • Rheumatoid Arthritis • Rheumatology

Henlius’ Rituximab Results Bolster RA Ambitions In China (Generics Bulletin - Informa) - "Shanghai Henlius Biotech has taken its groundbreaking Chinese rituximab biosimilar a step closer to securing a key rheumatoid arthritis indication."

Non-US regulatory • Rheumatoid Arthritis