Lost in Translation: Why Biologic Therapies for Intervertebral Disc Degeneration and Low Back Pain Have Not Reached the Clinic (Yet)

Background Biologic therapies for intervertebral disc degeneration (IDD) have shown strong preclinical promise, yet clinical translation for discogenic low back pain (LBP) remains limited. This gap reflects the inconsistent relationship between degeneration and pain, compounded by heterogeneous patient populations, insufficient phenotyping, and inadequate selection of truly discogenic LBP patients in current trials. Emerging evidence indicates that IDD and LBP comprise distinct biological endotypes, requiring matched therapeutic strategies, or “theratypes”, rather than uniform approaches. Methods In this narrative review, we critically examined the current evidence on biologic therapies for IDD, focusing on the translational gap between preclinical success and clinical outcomes. We analyzed key methodological and biological limitations, including patient heterogeneity, pain misclassification, inadequate phenotyping, and suboptimal trial design. Additionally, we reviewed emerging concepts such as disease phenotyping, mechanism‐based patient selection, and stage‐adapted therapeutic approaches. Discussion Multiple barriers hinder clinical translation of biologic therapies for IDD, including incomplete understanding of disc biology, limited intrinsic regenerative capacity, and a hostile tissue microenvironment. Preclinical models frequently fail to replicate the complexity of human pathology and pain, while clinical trials rely heavily on subjective outcomes and are often confounded by strong placebo effects. Furthermore, regulatory, logistical, and economic challenges limit widespread clinical adoption. Progress in the field will require a shift toward precision medicine approaches to align therapies with specific endotypes, pain phenotypes, and stages of IDD. Greater standardization, transparency, and community‐wide reporting practices are also essential to improve reproducibility. Conclusion Advancing biologic therapies for IDD will depend on the development of more precise and biologically informed clinical strategies. Improved patient stratification, better alignment between therapeutic mechanisms and disease biology, and the adoption of standardized and clinically meaningful outcome measures are critical. Despite recent progress, key pathophysiological mechanisms remain poorly understood, underscoring the need for rigorous and multidisciplinary research efforts.