Lilly's peresolimab Phase 2a rheumatoid arthritis trial published in The New England Journal of Medicine
Peresolimab met the primary efficacy endpoint in patients with refractory rheumatoid arthritis (RA)
Study evaluated a novel approach to treating patients with autoimmune diseases
"In the study, peresolimab showed meaningful results in refractory RA patients," said
Peresolimab is an investigational humanized immunoglobulin G1 monoclonal antibody that stimulates human programmed cell death protein 1 (PD-1), a checkpoint inhibitory receptor, that may induce physiological immune inhibitory pathways to restore immune homeostasis. RA, a form of rheumatologic disease, is a systemic autoimmune disease characterized by inflammation and progressive destruction of joints.2,3 While several treatment options exist, including the use of oral conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) — such as methotrexate, the current standard of care; and injectable, biological disease-modifying antirheumatic drugs (bDMARDs) — many patients do not reach or maintain their therapeutic goals.4,5,6 There remains a crucial unmet need to provide new treatment options for better overall patient care, particularly for refractory and biologic-experienced patients.
These data were first presented as a late-breaking abstract at the
At week 12, the change from baseline in the DAS28-CRP was significantly greater in the 700-mg peresolimab group than in the placebo group (least-squares mean change [±SE], −2.09±0.18 vs. −0.99±0.26; difference in change, −1.09 [95% confidence interval, −1.73 to −0.46]; P<0.001). The results of the analyses of secondary outcomes favored the 700-mg dose over placebo with respect to the ACR20 response, but not with respect to the ACR50 and ACR70 responses — defined as improvements from baseline of 20%, 50%, and 70% or more, respectively, in the numbers of tender and swollen joints and in at least three of five important domains — at week 12.
Noted improvements were seen in the Clinical Disease Activity Index (CDAI) in participants treated with both peresolimab doses compared to placebo. In addition, low disease activity was maintained through Week 24 in most patients achieving CDAI low disease activity at Week 14.
Adverse events were similar in the peresolimab and placebo groups. Treatment emergent events were mild or moderate in severity, with the most common events being infections and infestations, in addition to skin and subcutaneous tissue disorders. A single serious adverse event (worsening of hypothyroidism, 700 mg) was reported during the treatment period, which did not result in participant discontinuation from the study. There were no deaths reported in the study, and no reports of malignancy in participants receiving peresolimab.
The results support further clinical evaluation of peresolimab in rheumatologic diseases. Future studies will continue evaluating peresolimab as treatment for RA, including the ongoing RESOLUTION-1 (NCT05516758) clinical trial, a phase 2b study of peresolimab in adult participants with moderate-to-severe RA. Additionally,
Cautionary Statement Regarding Forward-Looking Statements
This press release contains forward-looking statements (as that term is defined in the Private Securities Litigation Reform Act of 1995) about peresolimab as a potential treatment for people with rheumatoid arthritis and the timeline for future readouts, presentations, and other milestones relating to peresolimab and its clinical trials, and reflects
- Melville, A. R., Kearsley-Fleet, L., Buch, M. H., & Hyrich, K. L. (2020). Understanding Refractory Rheumatoid Arthritis: Implications for a Therapeutic Approach. Drugs, 80(9), 849–857. https://doi.org/10.1007/s40265-020-01309-9
- Klareskog L, Catrina AI, Paget S.
Lancet. 2009;373:659-672. Hand Clinics, Advances in the Medical Treatment of Rheumatoid Arthritis, http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3135413/pdf/nihms305780.pdf. Accessed April 23, 2018.
- Hunter TM, et al. Rheumatol Int. 2017;37:1551–1557.
- Smolen JS, Aletaha D, McInnes IB.
- Sustained Rheumatoid Arthritis Remission is Uncommon in Clinical Practice, Arthritis Research & Therapy, http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3446437/. Accessed April 23, 2018.
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