Ex vivo comparative immunogenicity assessment (EVCIA) to determine relative immunogenicity in chronic plaque psoriasis in participants receiving Humira® or undergoing repeated switches between Humira® and AVT02

Article

作者: Haliduola, Halimu N ; Reznichenko, Nataliya ; Richter, Kathleen ; Guenzi, Eric ; Berti, Fausto ; Mazy, Aurélie ; Schockaert, Jana

SummaryImmunogenicity against biologic medicines is ubiquitous, and it is traditionally measured by the final humoral response. However, the onset of a sustained immunogenic response begins at the cellular level with activation of T cells and maturation of naïve B cells into plasma cells. Ex vivo comparative immunogenicity assessment (EVCIA) of cellular immunogenicity in participants with moderate-to-severe chronic plaque psoriasis in the AVT02-GL-302 study, who received either reference product (RP) alone (non-switching arm) or switched between RP and AVT02 (switching arm) after 1:1 randomization at week 12. Peripheral blood mononuclear cells (PBMCs) were collected and cryopreserved from 28 participants at: baseline (before treatment) (week 1); pre-randomization (week 12); and week 16 and week 28 in both switching and non-switching arms. PBMCs were thawed and re-exposed to either medium alone (negative control), RP, AVT02, keyhole limpet hemocyanin (KLH) (positive control), RP+KLH, or AVT02+KLH. Samples from 10 participants (predetermined average cell viability of 75% across all timepoints) from each arm were analyzed for cytokine release after 24 hours and for Th-cell proliferation, 6 days post-seeding. Until week 28, cytokine release and Th-cell proliferation was similar at all time points in both switching and non-switching arms. Overall cellular immune response was elevated post-KLH re-exposure at all timepoints. The comparable ex vivo cellular immunogenicity between switching and non-switching arms complements the confirmation of interchangeability in the main study. Given the sensitivity of novel EVCIA, detecting cellular immunogenicity could be a potential outcome in predicting the immunogenicity of biologic medicines.

2023-08-03·Expert Opinion on Biological Therapy

Randomized, double-blind, multicenter study to evaluate efficacy, safety, tolerability, and immunogenicity between AVT04 and the reference product ustekinumab in patients with moderate-to-severe chronic plaque psoriasis

Article

作者: Duijzings, Paul ; Reznichenko, Nataliya ; Ruffieux, Ruth ; Feldman, Steven R ; Stroissnig, Heimo ; Haliduola, Halimu N ; Berti, Fausto ; Leutz, Steffen ; Otto, Hendrik

BACKGROUNDThis study compared efficacy, safety, tolerability, pharmacokinetics (PK), and immunogenicity between AVT04 and reference product (RP) ustekinumab (Stelara®) in patients with moderate-to-severe chronic plaque psoriasis (PsO).PATIENTS AND METHODSThis multicenter, double-blind, 52-week study randomized patients in 1:2 ratio to AVT04 or RP. At week 16, responsive patients (≥50% improvement in psoriasis area and severity index (PASI)) previously on AVT04 continued on AVT04, while those on RP were re-randomized 1:1 to switch to AVT04 or stay on RP. The primary endpoint was a percent improvement in PASI from baseline to week 12. Therapeutic equivalence was demonstrated if the confidence interval (CI) for the adjusted difference in means was contained within the equivalence margins; ±10% (90%CI).RESULTSOf the 581 patients initially randomized (AVT04:RP, 194:387), 575 completed week 16 and 544 completed end of study visit. The percent PASI improvement for AVT04 vs RP was 87.3% vs 86.8% (CI: -2.14%, 3.01%); study met its primary endpoint. Efficacy, safety and PK profiles were comparable across treatment arms throughout the entire study duration, and the incidence of antibodies to ustekinumab had no clinically meaningful impact.CONCLUSIONThis study demonstrates the therapeutic equivalence between AVT04 and RP in patients with moderate-to-severe chronic PsO, with similar safety and tolerability.TRIAL REGISTRATIONNCT04930042; EudraCT Number: 2020-004,493-22.

2023-07-01·BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy

Assessing the Interchangeability of AVT02 and Humira^® in Participants with Moderate‑to‑Severe Chronic Plaque Psoriasis: Pharmacokinetics, Efficacy, Safety, and Immunogenicity Results from a Multicenter, Double-Blind, Randomized, Parallel-Group Study.

Article

作者: Kay, Richard ; Reznichenko, Nataliya ; Stroissnig, Heimo ; Haliduola, Halimu N ; Feldman, Steven R ; Sattar, Abid ; Ruffieux, Ruth ; Berti, Fausto ; Sobierska, Joanna ; Otto, Hendrik ; Dias, Roshan

BACKGROUNDThe US Food and Drug Administration (FDA) interchangeability guidelines state that the primary endpoint in a switching study should assess the impact of switching between the proposed interchangeable product and the reference product on clinical pharmacokinetics (PK) and pharmacodynamics (if available), as these assessments are generally sensitive to changes in immunogenicity and/or exposure that may arise due to switching. In addition, interchangeability designation requires no clinically meaningful difference in safety and efficacy of switching between the biosimilar and reference, compared with when using the reference product alone.OBJECTIVESThe aim of this study was to investigate the PK, immunogenicity, efficacy, and safety in participants undergoing repeated switches between Humira^® and AVT02 as part of a global interchangeable development program.METHODSThis multicenter, randomized, double-blind, parallel-group study in patients with moderate-to-severe plaque psoriasis comprises three parts: lead-in period (weeks 1-12), switching module (weeks 12-28), and the optional extension phase (weeks 28-52). Following the lead-in period during which all participants received the reference product (80 mg in week 1, followed by 40 mg every other week), participants with a clinical response of ≥ 75% improvement in the Psoriasis Area and Severity Index (PASI75) were randomized 1:1 to receive AVT02 alternating with the reference product (switching arm) or reference product only (non-switching arm). At week 28, participants who were PASI50 responders could opt to take part in an open-label extension phase receiving AVT02 up to week 50, with an end of study visit at week 52. PK, safety, immunogenicity, and efficacy were evaluated at various timepoints throughout the study for both switching and non-switching arms.RESULTSIn total, 550 participants were randomized to switching (277) and non-switching arms (273). The switching versus non-switching arithmetic least square means ratio [90% confidence intervals (CIs)] was 101.7% (91.4-112.0%) for the area under the concentration-time curve over the dosing interval from weeks 26-28 (AUC_{tau, W26-28}) and 108.1% (98.3-117.9%) for maximum concentration over the dosing interval from weeks 26-28 (C_{max, W26-28}). The 90% CIs for the switching versus non-switching arithmetic means ratio for primary endpoints AUC_{tau, W26-28} and C_{max, W26-28} were within the prespecified limits of 80-125%, demonstrating comparable PK profiles between groups. In addition, the PASI, Dermatology Life Quality Index, and static Physician's Global Assessment efficacy scores were highly similar for both treatment groups. There were no clinically meaningful differences between the immunogenicity and safety assessments of repeated switching between AVT02 and the reference product, versus the reference product alone.CONCLUSIONSThis study demonstrated that the risk, in terms of safety or diminished efficacy of switching between the biosimilar and the reference product, is not greater than the risk of using the reference product alone, as required by the FDA for interchangeability designation. Beyond the scope of interchangeability, a consistent long-term safety and immunogenicity profile, with no impact on the trough levels up to 52 weeks, was established.CLINICAL TRIAL REGISTRATIONNCT04453137; date of registration: 1 July 2020.

项与 Alvotech Germany GmbH 相关的新闻（医药）

2023-05-11

·GlobeNewswire-Health Care

Alvotech enters into commercialization agreement with Polifarma for proposed biosimilar to Eylea® (aflibercept)

Polifarma will commercialize AVT06, a proposed biosimilar to Eylea® (aflibercept), in Turkey Alvotech (NASDAQ: ALVO), a global biotech company specializing in the development and manufacture of biosimilar medicines for patients worldwide, today announced that it has entered into an exclusive agreement with Polifarma Ilac San. ve tic. A.S. (“Polifarma”) for the commercialization in Turkey of AVT06, a proposed biosimilar to Eylea® (aflibercept). “It is a pleasure to join forces with Polifarma in the commercialization of a potential therapy in eye disease,” said Robert Wessman, Chairman and CEO of Alvotech. “We are committed to providing better patient access to affordable biologics, and this agreement will allow us to better serve the growing and important Turkish market.” "Polifarma has been contributing to public health and the health sector in the world for 37 years with its motto of 'We stand by life'. This agreement with Alvotech allows us to expand our portfolio and further strengthen our position in the ophthalmology area. We are excited to have the opportunity to commercialize this product in Turkey," said Mehmet Asri, CEO of Polifarma. According to the agreement, Alvotech will be responsible for development and manufacture, while Polifarma will handle market registration and commercialization. AVT06 is a biosimilar candidate currently in clinical development. In July 2022, Alvotech announced the initiation of a patient study to compare AVT06 and Eylea® in terms of efficacy, safety, and immunogenicity in adult patients with neovascular (wet) age-related macular degeneration (AMD). About AVT06 AVT06 is a recombinant fusion protein and a biosimilar candidate to Eylea® (aflibercept), which binds vascular endothelial growth factors (VEGF), inhibiting the binding and activation of VEGF receptors, neovascularization, and vascular permeability. AVT06 is an investigational product and has not received regulatory approval in any country. Biosimilarity has not been established by regulatory authorities and is not claimed. About Polifarma Polifarma is the market leader of hospital products in Turkey and has a 37-year history, with 100% domestic capital. While developing its IV drug portfolio, Polifarma started to grow in the prescribed markets. As a leading brand in the Turkish health sector, Polifarma produces 350 million boxes per year at its 77 thousand square meter facility in Ergene/Tekirdağ. Besides manufacturing ampoules, vials and pre-filled syringes (PFS), Polifarma has 600 licensed products in all forms and 12 certificates in 15 therapeutic areas. Polifarma offers innovative solutions, such as Turkey's first lipid product and the world's first three-chamber parenteral nutrition solution and CAPD device. Exporting to 70 countries, Polifarma's vision is to become a global leader by 2025 and maintain its position with EU-GMP compliance and a commitment to quality and technology. About Alvotech Alvotech is a biotech company, founded by Robert Wessman, focused solely on the development and manufacture of biosimilar medicines for patients worldwide. Alvotech seeks to be a global leader in the biosimilar space by delivering high quality, cost-effective products, and services, enabled by a fully integrated approach and broad in-house capabilities. Alvotech’s current pipeline contains eight biosimilar candidates aimed at treating autoimmune disorders, eye disorders, osteoporosis, respiratory disease, and cancer. Alvotech has formed a network of strategic commercial partnerships to provide global reach and leverage local expertise in markets that include the United States, Europe, Japan, China, and other Asian countries and large parts of South America, Africa and the Middle East. Alvotech’s commercial partners include Teva Pharmaceuticals, a US affiliate of Teva Pharmaceutical Industries Ltd. (US), STADA Arzneimittel AG (EU), Fuji Pharma Co., Ltd (Japan), Advanz Pharma (EEA, UK, Switzerland, Canada, Australia and New Zealand), Cipla/Cipla Gulf/Cipla Med Pro (Australia, New Zealand, South Africa/Africa), JAMP Pharma Corporation (Canada), Yangtze River Pharmaceutical (Group) Co., Ltd. (China), DKSH (Taiwan, Hong Kong, Cambodia, Malaysia, Singapore, Indonesia, India, Bangladesh and Pakistan), YAS Holding LLC (Middle East and North Africa), Abdi Ibrahim (Turkey), Kamada Ltd. (Israel), Mega Labs, Stein, Libbs, Tuteur and Saval (Latin America) and Lotus Pharmaceuticals Co., Ltd. (Thailand, Vietnam, Philippines, and South Korea). Each commercial partnership covers a unique set of product(s) and territories. Except as specifically set forth therein, Alvotech disclaims responsibility for the content of periodic filings, disclosures and other reports made available by its partners. For more information, please visit www.alvotech.com. None of the information on the Alvotech website shall be deemed part of this press release. The content above comes from the network. if any infringement, please contact us to modify.