MADRID – To achieve positive trials with new agents in osteoarthritis, patient selection should be considered in the context of the primary endpoints, according to Philip G. Conaghan, MBBS, PhD, chair of musculoskeletal medicine at the University of Leeds (England).
In an interview, Dr. Conaghan explained that the issue has arisen with emerging agents that are designed for structural improvements with the expectation that symptom improvements will follow. Recapping a presentation he made at the European Congress of Rheumatology, he cautioned that the key aspects of trial design for these novel agents, including patient and endpoint selection, are particularly challenging.
As an example, Dr. Conaghan referred to the experience so far with the ongoing phase 2 FORWARD trial with sprifermin, a recombinant form of human fibroblast growth factor. In this study, sprifermin has already shown promise for growing cartilage, but the benefit accrues slowly, and there is no symptomatic improvement early in the course of treatment.
Based on the experience with FORWARD, much has been learned about a potential tension between structural and symptomatic endpoints in osteoarthritis, according to Dr. Conaghan. For one, it appears to be important to select patients most likely to achieve measurable structural improvements quickly to achieve a positive result in a reasonable period of time.
For another, it may be necessary to select symptom endpoints that reflect structural change while cautioning patients about the potential for a long delay before a clinical benefit is experienced.
In osteoarthritis, clinical benefit has been traditionally captured with relief of pain. Although an improvement in joint structure might be the best way to produce this result, this has to be proved. Reasonable and achievable endpoints are needed for emerging drugs with the potential to rebuild the joint not just to control pain, he said.
SOURCE: Gühring H et al. Ann Rheum Dis. Jun 2019;78(Suppl 2):70-1. Abstract OP0010. doi: 10.1136/annrheumdis-2019-eular.1216.