American College of Rheumatology Conference (ACR2020) Iberdomide/CC-220 Lupus Abstracts 5-9Nov2020 | BMY Message Board Posts


Bristol-Myers Squibb Co.

  BMY website

  • We hope everyone is having a spectacular day! And we trust everyone is starting to get the message: it's a new day here at IV and the future is looking brighter than ever. Please spread the word among your friends, colleagues and peers that we're back and more engaged than ever. Our ultimate goal is to transform this site into one of thought leadership in the realm of self-directed investing and that means attracting and retaining the best minds in the business.  And since many of you already fit the bill and move in the highest of circles, we are confident you will know who to invite to join you on our boards for serious investment discussion and debate. 

    Carry on! 

    Management 


BMY   /  Message Board  /  Read Message

 

 






Keyword
Subject
Between
and
Rec'd By
Authored By
Minimum Recs
  
Previous Message  Next Message    Post Message    Post a Reply return to message boardtop of board
Msg  4575 of 10115  at  10/14/2020 1:04:08 PM  by

JBWIN

The following message was updated on 10/14/2020 1:05:05 PM.

American College of Rheumatology Conference (ACR2020) Iberdomide/CC-220 Lupus Abstracts 5-9Nov2020

  
 
 

ABSTRACT NUMBER: 0851ACR Convergence 2020

Iberdomide Decreases B Cells and Plasmacytoid Dendritic Cells, Increases Regulatory T Cells and IL-2, and Has Enhanced Clinical Efficacy in Active Systemic Lupus Erythematosus Patients with High Aiolos or the IFN Gene Expression Signature

Peter Lipsky1, Ronald van Vollenhoven2, Thomas Dörner3, Victoria Werth4, Joan Merrill5, Richard Furie6, Milan Petronijevic7, Benito Velasco Zamora8, Maria Majdan9, Fedra Irazoque-Palazuelos10, Robert Terbrueggen11, Nikolay Delev12, Michael Weiswasser12, Shimon Korish12, Nataliya Agafonova12, Mark Stern13, Sarah Hersey13, Ying Ye13, Allison Gaudy12, Zhaohui Liu12, Shaojun Tang13 and Peter Schafer12, 1RILITE Foundation, Charlottesville, VA, 2Amsterdam University Medical Centers, Amsterdam, Netherlands, 3DRFZ and Charité University Hospitals, Berlin, Germany, 4University of Pennsylvania and the Michael J. Crescenz VA Medical Center, Philadelphia, PA, 5Oklahoma Medical Research Foundation, Oklahoma City, OK, 6Zucker School of Medicine at Hofstra/Northwell, Great Neck, NY, 7Military Medical Academy, Belgrade, Serbia, 8Instituto CER S.A., Buenos Aires, Argentina, 9Medical University of Lublin and Samodzielny Publicnzy Szpital Kliniczny Nr 4 w Lublinie, Lublin, Poland, 10Centro de Investigación y Tratamiento Reumatológico S.C, Miguel Hidalgo, Mexico, 11DxTerity Diagnostics Inc, Rancho Dominguez, 12Bristol Myers Squibb, Princeton, 13Bristol-Myers Squibb, Princeton

SESSION INFORMATION

Session Type: Abstract Session

Session Time: 3:00PM-3:50PM

Background/Purpose: Iberdomide is a high-affinity cereblon ligand that promotes ubiquitination and proteasomal degradation of Ikaros (IKZF1) and Aiolos (IKZF3), transcription factors linked to the genetic risk for systemic lupus erythematosus (SLE). Efficacy, safety, pharmacodynamics (PD), and pharmacokinetics (PK) of iberdomide were evaluated in a phase 2b study in patients (pts) with active SLE (NCT03161483).

Methods: Adults (N=288) with autoantibody-positive SLE by ACR criteria and with SLEDAI 2K score ≥6 were randomized (2:2:1:2) to oral iberdomide (0.45, 0.3, 0.15 mg) or placebo (PBO) daily for 24 wks, on standard background medications. Pts on PBO were re-randomized to iberdomide 0.3 and 0.45 mg at wk 24. Pts were stratified by SLEDAI 2K score (≥10/< 10) and oral corticosteroid (OCS) dose (≥10/< 10 mg/d; max OCS = 20 mg/d prednisone or equivalent). OCS tapering was permitted from wk 8-16. Study duration was 52 wks, and the primary endpoint was SLE Responder Index (SRI-4) response at wk 24. Efficacy analyses were based on the intent-to-treat population that included all pts who were randomized and received ≥1 dose of investigational product. Pts with missing data and treatment failures were imputed as nonresponders.

Results: Baseline demographic and disease characteristics were balanced between groups (Table 1). The primary endpoint at wk 24 was met: 54.3% of pts in iberdomide 0.45-mg group achieved SRI-4 response vs 34.9% in PBO group (stratified difference-19.4%; P=0.011). Notably greater SRI-4 responses, vs PBO, were seen starting at wk 16, especially in iberdomide 0.45- and 0.15-mg groups (Figure). Several secondary endpoints were also met. In those with SLEDAI 2K score ≥10, a greater proportion receiving iberdomide 0.45 mg also achieved SRI-4 response at wk 24 (66% vs 39%, nominal P=0.016). SRI-4 response in the prespecified biomarker-defined subset of baseline Aiolos-High was 64% vs 33% (P=0.011) and in pts who were Type 1 IFN-High was 60% vs 33% (P=0.006). At wk 24, iberdomide 0.45 mg was superior to PBO for CLASI-50 response in patients with subacute (92% vs 53%, P=0.035) and chronic cutaneous lupus (62% vs 28%, P=0.029), but not in the overall population. Other endpoints are shown in Table 2. Rates of AEs were 77% vs 65% for iberdomide all doses vs PBO; SAEs (6% vs 8%), severe AEs (4% vs 6%), serious infections (1%, both groups) and AEs leading to discontinuation (8% vs 7%) were comparable. The most common AEs with iberdomide (all doses vs PBO) were urinary tract infection (11%, 4%), upper respiratory tract infection (10%, 5%), neutropenia (8%, 2%), influenza (6%, 4%), nasopharyngitis (5%, 1%), and diarrhea (4%, 0%). Rates of neutropenia and infections were dose-dependent. Neutropenia was mostly grade (gr) 1 and 2 (gr 3, 6%; gr 4, 0.5%) and was reversible, not related to infection risk, and rarely led to discontinuation (2%). Neither systemic opportunistic infections nor tuberculosis occurred. There were 2 thromboembolic events observed with iberdomide and 2 with PBO.

Conclusion:

Iberdomide showed significant efficacy in the treatment of active SLE and was generally well tolerated. Enhanced effects were observed in 2 biomarker-defined populations (Aiolos-High, Type 1 IFN-High), providing a rationale for this novel mechanism in SLE.


Disclosure: J. Merrill, None; V. Werth, Biogen, 2, 5; R. Furie, AstraZeneca/MedImmune, 2, 5; R. van Vollenhoven, BMS, GSK, Lilly, Pfizer, Roche, UCB, 2, AbbVie, AstraZeneca, Biogen, Biotest, Celgene, Galapagos, Gilead, Janssen, Pfizer, Servier, UCB, 5, AbbVie, AstraZeneca, Biogen, Biotest, Celgene, Galapagos, Gilead, Janssen, Pfizer, Servier, UCB, 8; M. Petronijevic, None; B. Velasco Zamora, None; M. Majdan, None; F. Irazoque-Palazuelos, Pfizer, 5, 8, Bristol-Myers Squibb, 5, 8, Janssen, 5, 8, Takeda, 5, 8, Roche, 5, 8; M. Weiswasser, Bristol-Myers Squibb Company, 1, 3; S. Korish, Bristol-Myers Squibb Company, 1, 3; P. Schafer, Bristol-Myers Squibb Company, 1, 3; Z. Liu, Bristol-Myers Squibb Company, 1, 3; A. Gaudy, Bristol-Myers Squibb Company, 1, 3; N. Agafonova, Bristol-Myers Squibb Company, 1, 3; N. Delev, Bristol-Myers Squibb Company, 1, 3.
 
 

Advanced Search Results

  • Title
    ---
  • Authors and Affiliations
    Bristol Myers
 
SESSION INFORMATION

Session Type: Abstract Session

Session Time: 3:00PM-3:50PM

 
 
Background/Purpose: Iberdomide is a high-affinity cereblon ligand that promotes ubiquitination and proteasomal degradation of Ikaros (IKZF1) and Aiolos (IKZF3), transcription factors linked to the genetic risk for systemic lupus erythematosus (SLE). Efficacy, safety, pharmacodynamics (PD), and pharmacokinetics (PK) of iberdomide were evaluated in a phase 2b study in patients (pts) with active SLE (NCT03161483).
 
Methods: Adults (N=288) with autoantibody-positive SLE by ACR criteria and with SLEDAI 2K score ≥6 were randomized (2:2:1:2) to oral iberdomide (0.45, 0.3, 0.15 mg) or placebo (PBO) daily for 24 wks, on standard background medications. Pts on PBO were re-randomized to iberdomide 0.3 and 0.45 mg at wk 24. Pts were stratified by SLEDAI 2K score (≥10/< 10) and oral corticosteroid (OCS) dose (≥10/< 10 mg/d; max OCS = 20 mg/d prednisone or equivalent). OCS tapering was permitted from wk 8-16. Study duration was 52 wks, and the primary endpoint was SLE Responder Index (SRI-4) response at wk 24. Efficacy analyses were based on the intent-to-treat population that included all pts who were randomized and received ≥1 dose of investigational product. Pts with missing data and treatment failures were imputed as nonresponders.
 

Results: Baseline demographic and disease characteristics were balanced between groups (Table 1). The primary endpoint at wk 24 was met: 54.3% of pts in iberdomide 0.45-mg group achieved SRI-4 response vs 34.9% in PBO group (stratified difference-19.4%; P=0.011). Notably greater SRI-4 responses, vs PBO, were seen starting at wk 16, especially in iberdomide 0.45- and 0.15-mg groups (Figure). Several secondary endpoints were also met. In those with SLEDAI 2K score ≥10, a greater proportion receiving iberdomide 0.45 mg also achieved SRI-4 response at wk 24 (66% vs 39%, nominal P=0.016). SRI-4 response in the prespecified biomarker-defined subset of baseline Aiolos-High was 64% vs 33% (P=0.011) and in pts who were Type 1 IFN-High was 60% vs 33% (P=0.006). At wk 24, iberdomide 0.45 mg was superior to PBO for CLASI-50 response in patients with subacute (92% vs 53%, P=0.035) and chronic cutaneous lupus (62% vs 28%, P=0.029), but not in the overall population. Other endpoints are shown in Table 2. Rates of AEs were 77% vs 65% for iberdomide all doses vs PBO; SAEs (6% vs 8%), severe AEs (4% vs 6%), serious infections (1%, both groups) and AEs leading to discontinuation (8% vs 7%) were comparable. The most common AEs with iberdomide (all doses vs PBO) were urinary tract infection (11%, 4%), upper respiratory tract infection (10%, 5%), neutropenia (8%, 2%), influenza (6%, 4%), nasopharyngitis (5%, 1%), and diarrhea (4%, 0%). Rates of neutropenia and infections were dose-dependent. Neutropenia was mostly grade (gr) 1 and 2 (gr 3, 6%; gr 4, 0.5%) and was reversible, not related to infection risk, and rarely led to discontinuation (2%). Neither systemic opportunistic infections nor tuberculosis occurred. There were 2 thromboembolic events observed with iberdomide and 2 with PBO.

Conclusion:

Iberdomide showed significant efficacy in the treatment of active SLE and was generally well tolerated. Enhanced effects were observed in 2 biomarker-defined populations (Aiolos-High, Type 1 IFN-High), providing a rationale for this novel mechanism in SLE.

 
 
    
 
 


     e-mail to a friend      printer-friendly     add to library      
|  
Recs: 10  
   Views: 145 []
Previous Message  Next Message    Post Message    Post a Reply return to message boardtop of board




Financial Market Data provided by
.
Loading...