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ACR 2009: Benlysta outshines disappointing rheumatoid arthritis data

Posted Jun 10 2010 4:05am
HTML clipboardThis year's American College of Rheumatology Annual Conference in Philadelphia. No ground-breaking data for rheumatoid arthritis therapies were presented; instead, systemic lupus erythematosus stole the limelight.
 
 ACR 2009: Benlysta outshines disappointing rheumatoid arthritis data
 
 This year's American College of Rheumatology Annual Conference in Philadelphia. No ground-breaking data for rheumatoid arthritis therapies were presented; instead, systemic lupus erythematosus stole the limelight. Human Genome Sciences' Benlysta in particular generated a stir, being the first drug in this indication to generate positive data at Phase III. ( http://www.bharatbook.com/detail.asp?id=128392&rt=Pipeline-Insight-Disease-Modif )
 
 Benlysta looks set to make SLE history
 
 After a shift in supremacy following rituximab's failure and belimumab's success in systemic lupus erythematosus (SLE), It now believes that Benlysta (belimumab; Human Genome Sciences) holds the greatest potential to become the first drug approved for this difficult to manage disease for over 50 years. At the 73rd annual conference of the American College of Rheumatology (ACR 2009), Human Genome Sciences and GlaxoSmithKline presented the full clinical trial data for Benlysta in SLE, as well as combined four-year safety data for the drug. At 1mg/kg and 10mg/kg, Benlysta achieved a statistically significant reduction in the SLE Responder Index at week 52 versus placebo. The observed decrease was rapid, as early as 16 weeks, and sustained. The drug also had a significant steroid-sparing impact, while showing meaningful improvements in other measures such as fatigue, physicians' global assessment and delayed time to first SLE flare. In terms of safety, Benlysta was comparable with placebo for serious adverse events and drug discontinuations.
 
 Clinical data for new anti-TNFs failed to make an impact
 
 The two new anti-TNF therapies on show at the conference, Simponi (golimumab; Centocor Ortho Biotech/Schering-Plough/Mitsubishi Tanabe) and Cimzia (certolizumab, UCB), did not present any significantly new clinical data to write home about. In fact, most data were recycled from the earlier EULAR meeting in Copenhagen in June 2009.
 
 Centocor Ortho Biotech, however, presented its long-awaited radiographic progression data from the GO-BEFORE (methotrexate-naive patients) and GO-FORWARD (methotrexate-inadequate responders) Phase III trials. While both 50mg and 100mg Simponi, in combination with methotrexate, showed clinically meaningful inhibition of radiographic progression at 52 weeks in GO-BEFORE, this was not the case in the GO-FORWARD study. Despite these disappointing data, Centocor Ortho Biotech's strong marketing presence and high number of abstracts all underpinned the company's efforts to get Simponi noticed six months after its US launch, but it is skeptical about the impact of this me-too brand. The underwhelming data presented at ACR 2009 will do little to change this outlook.
 
 Oral small molecules remain on course for the treatment of RA
 
 Pfizer's JAK3 inhibitor CP-690,550 continues to draw a crowd at the rheumatology meetings, and this year's ACR conference was no exception. The week 24 data from two Phase II rheumatoid arthritis (RA) studies looking at either CP-690,550 monotherapy or combination with methotrexate suggest that the drug has sustained efficacy. Importantly, the safety profile is consistent with previous data and no new safety signals are apparent. These rapid and sustained efficacy data, together with the consistent safety data, suggest that CP-690,550 will have a place in the future treatment of RA. However, recent report, 'Pipeline Insight: Disease Modification in Rheumatoid Arthritis', maintains that cost and product positioning remain vital factors for this drug's eventual success.
 
 Rigel Pharmaceuticals presented data for its Syk inhibitor R788 from two Phase II studies in the late-breaking abstract session. Of note were the company's explanations for the drug failing its TASKi3 Phase IIb trial in biologic-failure RA patients. Problems with ESR/CRP differences at baseline and imbalances between active and placebo groups for prior biologic exposure seem to account for the trial failure. Rigel Pharmaceuticals indicated that although it is not a high priority for the company, any future studies in the biologic-failure setting will receive more scrutiny in terms of biomarkers and better stratification of patients with prior biologic treatment. The safety data for R788 suggested no new safety signals, which sees as encouraging. Attention will now focus on Rigel Pharmaceuticals's meetings with the FDA to discuss the next steps of development, as well as whether the company can find a much needed partner.
 
 Data for novel pipeline agents met with mixed reception
 
 In a session focusing on novel therapies in development for the treatment of RA, several new biologic drugs presented early-phase clinical data. These included anti-BAFF antibody (LY2127399; Eli Lilly), anti-IL17A antibody (AIN457; Novartis), anti-GM-CSFR antibody (CAM-3001; Medimmune), and a new folate antagonist, CH104 (Chelsea Therapeutics). While it believes that the data for Novartis' AIN457 and Eli Lilly's IL-17 targeted antibodies were received well, the data for CAM-3001 and CH-1504 left rheumatologists unconvinced of their potential. The low efficacy results for both drugs left unanswered questions as to whether there was really a rationale for taking these candidates into further study.
 
 Biomarkers appeared to be of high interest at the conference
 
 This year's ACR conference focused on biomarkers in rheumatology, an area which will be investigating later this year with a report planned for publication by the end of 2009. Of interest was the fact that Centocor Ortho Biotech has identified several key biomarkers associated with response to Simponi in RA, psoriatic arthritis and ankylosing spondylitis. While this is still just an association, the company looks to be shifting towards predicting which patients will respond best to its new TNF inhibitor. On a similar note, a Japanese group identified an accurate single-nucleotide polymorphism algorithm to predict response, as well as adverse events, to Actemra/RoActemra (tocilizumab; Roche/Chugai). While it does not believe that this is in current use in clinical practice, the technique could be used to tailor-make an approach to the use of Actemra/RoActemra.
 
 Related research
 
 • Pipeline Insight: Disease Modification in Rheumatoid Arthritis - New drug targets compete in crowded market
  http://www.bharatbook.com/detail.asp?id=128392&rt=Pipeline-Insight-Disease-Modif
 
 • Commercial Insight: Disease modification in rheumatoid arthritis - Anti-TNFs defend first-line biologic position despite competition
  http://www.bharatbook.com/detail.asp?id=91885&rt=Commercial-Insight-Disease-Modi
 
 • Pricing and Reimbursement: Innovative Risk-Sharing Strategies
  http://www.bharatbook.com/detail.asp?id=103566&rt=Pricing-and-Reimbursement-Inno
 
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