Delving into the Latest Updates on Lulizumab pegol with Synapse

Overview

Basic Info

Drug Type

Monoclonal antibody

Synonyms

Lulizumab

Target

CD28

Action

inhibitors

Mechanism

CD28 inhibitors(T-cell-specific surface glycoprotein CD28 inhibitors)

Therapeutic Areas

Urogenital Diseases

Active Indication

Kidney Diseases

Inactive Indication

Primary Sjögren's syndromeRenal transplant rejectionSystemic Lupus Erythematosus

Originator Organization

Bristol Myers Squibb Co.

Active Organization

Bristol Myers Squibb Co.

Inactive Organization-

License Organization-

Drug Highest PhasePhase 1/2

First Approval Date-

Regulation-

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Structure/Sequence

Sequence Code 198370L

Source: *****

Purpose of reviewCalcineurin inhibitors (CNIs) are central to immunosuppression in kidney transplantation (KT), improving short-term outcomes but falling short in enhancing long-term outcomes due to cardiovascular, metabolic, and renal complications. Belatacept, an FDA-approved costimulation blocker, offers a less toxic alternative to CNIs but is limited by its intravenous administration and reduced efficacy in high-immunological-risk patients.Recent findingsEmerging therapies target more specific pathways to improve efficacy and accessibility. Abatacept, a first-generation cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) immunoglobulin, has shown favorable outcomes in small studies. VEL-101 and Lulizumab selectively block CD28 while preserving CTLA-4 signaling, showing promise in early trials. In the CD40/CD40L pathway, results have been mixed. Iscalimab (CD40 antibody) was inferior to tacrolimus in Phase 2 trials, and Bleselumab (CD40 antibody) showed variable rejection rates despite being noninferior to tacrolimus. CD40L-targeting agents such as TNX-1500, Tegoprubart, and Dazodalibep have demonstrated promising efficacy and safety in rejection prophylaxis.SummaryThe focus in transplantation is shifting toward safer, long-term therapies with greater accessibility. Investigational agents with subcutaneous delivery methods could overcome logistical challenges, improve adherence, and redefine posttransplant care. These advancements in costimulation blockade may enhance long-term graft survival and transform the management of KT recipients.

01 Feb 2024·CPT: Pharmacometrics & Systems Pharmacology

Model‐based meta‐analysis using latent variable modeling to set benchmarks for new treatments of systemic lupus erythematosus

Article

Author: Venkatakrishnan, Karthik ; French, Jonathan ; Mateo, Cristina Vazquez ; Klopp-Schulze, Lena ; Li, Ying ; Roy, Sanjeev ; Garcia, Ramon ; Gillespie, William R ; Goteti, Kosalaram ; Benincosa, Lisa ; Guenther, Oliver

AbstractSeveral investigational agents are under evaluation in systemic lupus erythematosus (SLE) clinical trials but quantitative frameworks to enable comparison of their efficacy to reference benchmark treatments are lacking. To benchmark SLE treatment effects and identify clinically important covariates, we developed a model‐based meta‐analysis (MBMA) within a latent variable model framework for efficacy end points and SLE composite end point scores (BILAG‐based Composite Lupus Assessment and Systemic Lupus Erythematosus Responder Index) using aggregate‐level data on approved and investigational therapeutics. SLE trials were searched using PubMed and www.clinicaltrials.gov for treatment name, SLE and clinical trial as search criteria that resulted in four data structures: (1) study and investigational agent, (2) dose and regimen, (3) baseline descriptors, and (4) outcomes. The final dataset consisted of 25 studies and 81 treatment arms evaluating 16 different agents. A previously developed (K Goteti et al. 2022) SLE latent variable model of data from placebo arms (placebo + standard of care treatments) was used to describe aggregate SLE end points over time for the various SLE placebo and treatment arms in a Bayesian MBMA framework. Continuous dose‐effect relationships using a maximum effect model were included for anifrolumab, belimumab, CC‐220 (iberdomide), epratuzumab, lulizumab pegol, and sifalimumab, whereas the remaining treatments were modeled as discrete dose effects. The final MBMA model was then used to benchmark these compounds with respect to the maximal efficacy on the latent variable compared to the placebo. This MBMA illustrates the application of latent variable models in understanding the trajectories of composite end points in chronic diseases and should enable model‐informed development of new investigational agents in SLE.

01 Jan 2021·Kidney InternationalQ1 · MEDICINE

Preoperative carfilzomib and lulizumab based desensitization prolongs graft survival in a sensitized non-human primate model

Q1 · MEDICINE

Article

Author: Ezekian, Brian ; Leopardi, Frank ; Collins, Bradley ; Schroder, Paul M ; Kwun, Jean ; Barbas, Andrew ; Schmitz, Robin ; Farris, Alton B ; Song, Mingqing ; Yoon, Janghoon ; Fitch, Zachary W ; Manook, Miriam ; Choi, Ashley Y ; Knechtle, Stuart J

Sensitized patients are difficult to transplant due to pre-formed anti-donor immunity. We have previously reported successful desensitization using carfilzomib and belatacept in a non-human primate (NHP) model. Here we evaluated selective blockade of the co-stimulatory signal (CD28-B7) with Lulizumab, which preserves the co-inhibitory signal (CTLA4-B7). Five maximally MHC-mismatched pairs of NHPs were sensitized to each other with two sequential skin transplants. Individuals from each pair were randomized to either desensitization with once-weekly Carfilzomib (27mg/m² IV) and Lulizumab (12.5mg/kg SC) over four weeks, or no desensitization (Control). NHPs then underwent life-sustaining kidney transplantation from their previous skin donor. Rhesus-specific anti-thymocyte globulin was used as induction therapy and immunosuppression maintained with tacrolimus, mycophenolate, and methylprednisolone. Desensitized subjects demonstrated a significant reduction in donor-specific antibody, follicular helper T cells (CD4⁺PD-1⁺ICOS⁺), and proliferating B cells (CD20⁺Ki67⁺) in the lymph nodes. Interestingly, regulatory T cell (CD4⁺CD25⁺CD127^lo) frequency was maintained after desensitization in addition to increased frequency of naïve CD4 T cells (CCR7⁺CD45RA⁺) and naïve B cells (IgD⁺CD27^-CD20⁺) in circulation. This was associated with significant prolongation in graft survival (MST = 5.8 ± 4.0 vs. 64.8 ± 36.3; p<0.05) and lower antibody-mediated rejection scores compared to control animals. However, all desensitized animals eventually developed AMR and graft failure. Desensitization with CFZ and Lulizumab improves allograft survival in allosensitized NHPs, by transient control of the germinal center and shifting of the immune system to a more naive phenotype. This regimen may translate into clinical practice to improve outcomes of highly sensitized transplant patients.

100 Deals associated with Lulizumab pegol

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External Link

KEGG	Wiki	ATC	Drug Bank
-	Lulizumab pegol	-	DB15441

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Systemic Lupus Erythematosus	Phase 3	Puerto Rico	Bristol Myers Squibb Co.	13 Nov 2014
Systemic Lupus Erythematosus	Phase 3	Japan	Bristol Myers Squibb Co.	13 Nov 2014
Systemic Lupus Erythematosus	Phase 3	Romania	Bristol Myers Squibb Co.	13 Nov 2014
Systemic Lupus Erythematosus	Phase 3	Poland	Bristol Myers Squibb Co.	13 Nov 2014
Systemic Lupus Erythematosus	Phase 3	France	Bristol Myers Squibb Co.	13 Nov 2014
Systemic Lupus Erythematosus	Phase 3	Peru	Bristol Myers Squibb Co.	13 Nov 2014
Systemic Lupus Erythematosus	Phase 3	Canada	Bristol Myers Squibb Co.	13 Nov 2014
Systemic Lupus Erythematosus	Phase 3	Netherlands	Bristol Myers Squibb Co.	13 Nov 2014
Systemic Lupus Erythematosus	Preclinical	Chile	Bristol Myers Squibb Co.	13 Nov 2014
Systemic Lupus Erythematosus	Discovery	Germany	Bristol Myers Squibb Co.	13 Nov 2014

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02265744 (CTgov)	Phase 2	Systemic Lupus Erythematosus	730	BMS-931699 (Experimental: 12.5mg SC BMS-931699 Weekly)	gjhlntmfxk(kklevdkrxh) = tgwvjdsije hxumjwuzfm (glrkesqhmo, jbycecndgb - deqcuvyyzr) View more	-	04 Jan 2019
				BMS-931699 (Experimental: 12.5mg SC BMS-931699 Every Other Week)	gjhlntmfxk(kklevdkrxh) = ozwudsjftf hxumjwuzfm (glrkesqhmo, tttbnheohe - dtykinajyg) View more

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Approval

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Biosimilar

Competitive landscape of biosimilars in different countries/locations. Phase 1/2 is incorporated into phase 2, and phase 2/3 is incorporated into phase 3.

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Competitive landscape of biosimilars in different countries/locations. Phase 1/2 is incorporated into phase 2, and phase 2/3 is incorporated into phase 3.

Regulation

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Lulizumab pegol

Overview

Basic Info

Structure/Sequence

Related

External Link

R&D Status

Clinical Result

Translational Medicine

Deal

Core Patent

Clinical Trial

Approval

Biosimilar

Regulation