sprifermin (AS-902330) / EMD Serono, Nordic Biosci, Formation Bio - LARVOL DELTA

STRUCTURAL EFFICACY OF INTRA-ARTICULAR SPRIFERMIN TREATMEN ON KNEE OSTEOARTHRITIS AS A FUNCTION OF SYMPTOMATIC AND RADIOGRAPHIC DISEASE SEVERITY - A POST-HOC ANALYSIS FROM THE FORWARD PHASE 2 RANDOMIZED CONTROLLED TRIAL (EULAR 2025) - No abstract available

Clinical • P2 data • Retrospective data • Immunology • Osteoarthritis • Pain • Rheumatology

Advances and Challenges in the Pursuit of Disease-Modifying Osteoarthritis Drugs: A Review of 2010-2024 Clinical Trials. (PubMed, Biomedicines) - " Eleven DMOAD candidates are reviewed and critically analyzed for their potential benefit in OA treatment-Lorecivivint (SM04690), TissueGene-C, Cindunistat (SD-6010), Sprifermin, UBX0101, TPX-100, GLPG1972/S201086, Lutikizumab (ABT-981), SAR113945, MIV-711, and LNA043-and relevant challenges to their development are discussed. Six DMOADs have demonstrated statistically significant evidence of a structural or symptomatic benefit without major safety concerns in phase II and III randomized controlled trials post-2010."

Journal • Review • Developmental Disorders • Immunology • Osteoarthritis • Pain • Rheumatology

Exploring a Novel Outcome Measure of Symptom Progression in Knee Osteoarthritis Utilizing a Large Randomized Trial. (PubMed, Osteoarthritis Cartilage) - P2 | "The symptom progression endpoint discriminated between placebo and treatment responses in a post hoc analysis of a Phase 2 investigational DMOAD KOA trial. The endpoint requires validation and further exploration in DMOAD clinical trials."

Journal • Immunology • Musculoskeletal Diseases • Orthopedics • Osteoarthritis • Pain • Rheumatology

Unbiased analysis of knee cartilage thickness change over three years after sprifermin vs. placebo treatment - A post-hoc analysis from the phase 2B FORWARD study. (PubMed, Osteoarthr Cartil Open) - P2 | "FORWARD is the first study evaluating post-treatment benefits of a potential disease modifying osteoarthritis drug. Cartilage thickness gained with 100 ​μg sprifermin at Y2 is maintained to Y5 and thus appears viable and sustainable.This is a post-hoc analysis of the FORWARD trial: ClinicalTrials.gov Identifier: NCT01919164."

Journal • P2b data • Retrospective data • Immunology • Osteoarthritis • Pain • Rheumatology

A comprehensive review of phase 2/3 trials in osteoarthritis: an expert opinion. (PubMed, Expert Opin Emerg Drugs) - "Methotrexate has been shown to be beneficial when used in the correct patient cohort (MRI proven synovitis). Sprifermin has the longest follow-up data of 5 years and has been shown to reduce loss of MRI-measured cartilage thickness and pain scores."

Journal • P2/3 data • Review • Immunology • Osteoarthritis • Pain • Rheumatology

UNBIASED ANALYSIS OF KNEE CARTILAGE THICKNESS CHANGE OVER THREE YEARS POST-TREATMENT WITH SPRIFERMIN VS. PLACEBO – A POST-HOC ANALYSIS FROM THE PHASE II FORWARD STUDY (EULAR 2024) - "FORWARD is the first study to evaluate the longer-term benefit of a potential anabolic DMOAD on cartilage structure, for 3.5 years after the last treatment [2]. All sprifermin groups lost cartilage throughout the post-treatment period, but not at greater rates than the placebo group during the same or the treatment period. These observations allow us to infer indirectly that the cartilage accumulated during anabolic sprifermin treatment appears structurally viable and mechanically competent post-treatment."

Clinical • P2 data • Retrospective data • Immunology • Osteoarthritis • Pain • Rheumatology

IS DETECTION OF DISEASE-MODIFYING OSTEOARTHRITIS DRUG TREATMENT MORE EFFECTIVE WHEN PERFORMING CARTILAGE MORPHOMETRY WITHOUT BLINDING TO MR IMAGE ACQUISITION ORDER? (PubMed, Osteoarthritis Cartilage) - "These results do not reveal that detection of proposed DMOAD treatment is enhanced with MRIs read unblinded to order; rather, the sensitivity is similar to blinded analysis. Choices on blinded vs. unblinded analysis may thus be based on other criteria."

Journal • Immunology • Osteoarthritis • Pain • Rheumatology

IS DETECTION OF DMOAD TREATMENT MORE EFFECTIVE WHEN PERFORMING QUANTITATIVE CARTILAGE ANALYSIS WITH UNBLINDED IMAGE ACQUISITION ORDER? (OARSI 2024) - "In a phase II double-blind, randomized controlled trial (FORWARD) , sprifermin demonstrated anabolic cartilage modification over 24 months (M) in knee OA patients; MRIs were read with blinding to time point. Here we test the hypothesis that effect sizes are greater when the analysis is performed unblinded to acquisition order."

Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology

Clinical and Imaging Characteristics of Individuals Who Underwent Knee Replacement During Years 3 to 5 in the FORWARD Study: A Post Hoc Analysis (ACR Convergence 2023) - P1, P2 | "Pts treated with IA sprifermin 100 µg had a lower incidence of KR than those receiving PBO or sprifermin 30 µg, with the incidence of KR being similar in the latter groups. Although the overall incidence of KR was low, differences in clinical and structural features (especially in the medial compartment) of KOA were apparent at BL and W104, with less symptomatic improvement and more structural worsening at W104, in those who received KR compared to those who did not. These findings need to be confirmed in a prospective study."

Clinical • Retrospective data • Immunology • Musculoskeletal Diseases • Orthopedics • Osteoarthritis • Pain • Rheumatology • FGF18

Effects of Sprifermin on a Novel Outcome of Osteoarthritis Symptom Progression: Post Hoc Analysis of the FORWARD Study (ACR Convergence 2023) - "These post hoc results support that sprifermin may prevent symptomatic progression of KOA, with benefits seen in both ITT and SAR populations for the sprifermin 100 µg combined group. Further study is needed to confirm the symptomatic and structural benefits of sprifermin. As differences between the sprifermin- and PBO-treated groups were detectable in a 3-year time frame, time to symptomatic progression of KOA could be a meaningful endpoint for a DMOAD trial."

Retrospective data • Immunology • Musculoskeletal Diseases • Orthopedics • Osteoarthritis • Pain • Rheumatology • FGF18

Impact of Sprifermin on Denuded Areas of Subchondral Bone (dABs): A Post Hoc Analysis of the FORWARD Study (ACR Convergence 2023) - "The presence of dAB appears to be associated with more severe radiographic OA and structural progression of KOA. Sprifermin treatment, particularly at the highest dose, appears to slow the increase (worsening) of dAB compared to PBO, especially in the medial compartment. Further evaluation of these findings and the relationship of dAB with symptomatic outcomes is warranted, including in prospective clinical trials."

Retrospective data • Immunology • Musculoskeletal Diseases • Orthopedics • Osteoarthritis • Pain • Rheumatology • FGF18

Computer-assisted stabilization of fibroblast growth factor FGF-18. (PubMed, Comput Struct Biotechnol J) - "However, recent phase 2 clinical trial results of sprifermin (recombinant FGF18) indicate insufficient efficacy...Moreover, the FGF18-E4 maintained mitogenic activity after 1-week incubation at 37 °C and 1-day at 50 °C. Additionally, the inserted mutations did not affect its binding to the fibroblast growth factor receptors, making FGF18-E4 a promising candidate for advancing FGF-based osteoarthritis treatment."

Journal • Immunology • Osteoarthritis • Pain • Rheumatology • FGF • FGF18 • FGFR

Effects of Sprifermin on a Novel Outcome of Osteoarthritis Symptom Progression: Post-hoc Analysis of the FORWARD Randomized Trial (EULAR 2023) - "As differences between the sprifermin- and PBO-treated groups were detectable in a 3-year time frame, time to symptomatic progression of KOA could be a meaningful endpoint for an investigational DMOAD trial. Symptomatic and structural benefits of sprifermin need to be confirmed in the planned Phase 2b SPRING study."

Clinical • Retrospective data • Immunology • Musculoskeletal Diseases • Orthopedics • Osteoarthritis • Pain • Rheumatology • FGF18

Latest insights in disease-modifying osteoarthritis drugs development. (PubMed, Ther Adv Musculoskelet Dis) - "Most biologics (including interleukin-1 (IL-1) and tumor necrosis factor (TNF) inhibitors), sprifermin, and bisphosphonates failed to yield satisfactory results when treating OA...We summarize in this review the efficacy and safety profiles of various DMOADs targeting cartilage, synovitis, and subchondral bone endotypes in phase 2 and 3 clinical trials. To conclude, we summarize the reasons for clinical trial failures in OA and suggest possible solutions."

Journal • Review • Immunology • Oncology • Osteoarthritis • Pain • Rheumatology

Cartilage Formation Trajectories From Newborns To Adult Life Reveal A Low Repair Endotype Of Oa Patients, As Quantified By Type Ii Collagen Formation (OARSI 2023) - "Furthermore, patients with low serum levels of PRO-C2 were more likely to respond to Sprifermin, a recombinant FGF18 analog, compared to patients with high levels of PRO-C2...Although cartilage attempts to restore in OA, damaged cartilage has a poor capacity for regeneration. In the current study, we investigated if low cartilage formation assessed by serum PRO-C2 is associated with low repair capacity of cartilage."

Clinical • Immunology • Osteoarthritis • Pain • Rheumatology

The Current Role of Disease-modifying Osteoarthritis Drugs. (PubMed, Arch Bone Jt Surg) - "It was encountered that many publications have analyzed the impact of several DMOAD methods, including anti-cytokine therapy (tanezumab, AMG 108, adalimumab, etanercept, anakinra), enzyme inhibitors (M6495, doxycycline, cindunistat, PG-116800), growth factors (bone morphogenetic protein-7, sprifermin), gene therapy (micro ribonucleic acids, antisense oligonucleotides), peptides (calcitonin) and others (SM04690, senolitic, transient receptor potential vanilloid 4, neural EGFL-like 1, TPCA-1, tofacitinib, lorecivivint and quercitrin). In conclusion, even though DMOADs seem promising, their clinical effectiveness has not yet been demonstrated for managing OA. Until forthcoming studies can proved the medications' capacity to repair and regenerate tissues affected by OA, physicians should keep using treatments that only intend to alleviate pain."

Journal • Review • Gene Therapies • Immunology • Musculoskeletal Pain • Orthopedics • Osteoarthritis • Pain • Rheumatology • NELL1

How Effective Are Non-Operative Intra-Articular Treatments for Bone Marrow Lesions in Knee Osteoarthritis in Adults? A Systematic Review of Controlled Clinical Trials. (PubMed, Pharmaceuticals (Basel)) - "Two studies of sprifermin, one of autologous protein solution (APS) and one of high-dose TissueGene-C, reported a positive effect on OA-BMLs under 1-year follow-up...Overall, we found mixed evidence on the efficacy of intra-articular therapy for improving OA-BMLs in KOA. Additional studies with long-term follow-up are needed to confirm the effect of various intra-articular therapies on OA-BMLs in KOA."

Clinical • Journal • Review • Immunology • Musculoskeletal Pain • Osteoarthritis • Pain • Rheumatology

Preclinical Use of FGF-18 Augmentation for Improving Cartilage Healing Following Surgical Repair: A Systematic Review. (PubMed, Cartilage) - "This systematic review provides evidence that rhFGF-18 significantly improves cartilage healing at 6 months postoperatively following microfracture or osteochondral defect repair in preclinical randomized controlled trials."

Journal • Preclinical • Review • Musculoskeletal Diseases • Orthopedics • Transplantation • FGF

Clinical efficacy and safety of monoclonal antibody against Nerve Growth Factor and Fibroblast Growth Factor-18 therapy of osteoarthritis (EULAR 2022) - "Currently osteoarthritis treatment includes acetaminophen, NSAIDs and/or opioids, intra-articular corticosteroid injections...Among 23 studies, 16 used anti-NGF monoclonal antibodies (Tanezumab, Fasinumab, Fulranumab), and 7 used recombinant human FGF-18 (Sprifermin)... In recent years significant progress has been achieved in search for pathogenetic therapy of OA. Based on the results of current research findings, NGF inhibitors relieved pain and enhance joint function and may be considered as the most effective for functional improvement. FGF-18 decrease the cartilage loss and may improve cartilage thickness."

Clinical • Back Pain • Gene Therapies • Immunology • Infectious Disease • Musculoskeletal Diseases • Musculoskeletal Pain • Osteoarthritis • Otorhinolaryngology • Pain • Peripheral Neuropathic Pain • Respiratory Diseases • Rheumatology • Sinusitis • NGF

Tc-NTP 15-5 is a companion radiotracer for assessing joint functional response to sprifermin (rhFGF-18) in a murine osteoarthritis model. (PubMed, Sci Rep) - "Under sprifermin, Tc-NTP 15-5 uptake in pathological knees was significantly increased compared to controls, at 7-, 12- and 24-weeks, and consistent with proteoglycan increase measured 5 weeks post-surgery, as a sign of cartilage matrix remodelling. Our work highlights the potential of Tc-NTP 15-5 as an imaging-based companion to monitor cartilage remodelling in OA and DMOAD response."

Journal • Preclinical • Immunology • Osteoarthritis • Pain • Rheumatology

The recombinant human fibroblast growth factor-18 (sprifermin) Improves Tendon-to-Bone Healing by promoting chondrogenesis In a Rat Rotator Cuff Repair Model. (PubMed, J Shoulder Elbow Surg) - "rhFGF-18 promoted chondrogenesis in the hBMSCs in vitro. rhFGF-18/SA improved tendon-to-bone healing in the rats by promoting regeneration of the fibrocartilage enthesis. rhFGF-18 (sprifermin) may be beneficial for improving tendon-to-bone healing after rotator cuff repair."

Journal • Preclinical • FGF • SOX9 • YBX1

TrialSpark licenses sprifermin, an investigational first-in-class disease modifying treatment for osteoarthritis, from Merck KGaA, Darmstadt, Germany and announces formation of High Line Bio (PRNewswire) - "TrialSpark announced today the formation of High Line Bio following the acquisition of worldwide rights to sprifermin from Merck KGaA, Darmstadt, Germany....TrialSpark will be fully responsible for future development and commercialization of sprifermin. As part of the agreement Merck KGaA, Darmstadt, Germany will receive an upfront payment as well as equity in High Line Bio, and is eligible for clinical and commercial milestone payments in addition to royalties on future net sales. Full financial terms were not disclosed."

Licensing / partnership • CNS Disorders • Osteoarthritis • Pain

Sprifermin: Effects on Cartilage Homeostasis and Therapeutic Prospects in Cartilage-Related Diseases. (PubMed, Front Cell Dev Biol) - "Sprifermin (recombinant human FGF18, rhFGF18) is an effective DMOAD, which can not only promote the proliferation of articular chondrocyte and the synthesis of extracellular matrix, increase the thickness of cartilage in a dose-dependent manner, but also inhibit the activity of proteolytic enzymes and remarkedly slow down the degeneration of cartilage. This paper reviews the unique advantages of Sprifermin in repairing cartilage injury and improving cartilage homeostasis, aiming to provide an important strategy for the effective prevention and treatment of cartilage injury-related diseases."

Journal • Review • Immunology • Osteoarthritis • Pain • Rheumatology • Transplantation

Low levels of type II collagen formation (PRO-C2) are associated with response to sprifermin: A pre-defined, exploratory biomarker analysis from the FORWARD study. (PubMed, Osteoarthritis Cartilage) - "Patients with low serum PRO-C2 levels lost more cartilage thickness over time and grew more cartilage in response to sprifermin vs. a placebo when compared to patients with high PRO-C2 levels."

Biomarker • Journal • Immunology • Osteoarthritis • Pain • Rheumatology • MRI

Sprifermin: a recombinant human fibroblast growth factor 18 for the treatment of knee osteoarthritis. (PubMed, Expert Opin Investig Drugs) - "Current studies show good tolerability and no safety concerns. Well-designed phase 3 clinical trials are required to examine its effects on symptoms and cartilage loss in knee OA."

Journal • Immunology • Osteoarthritis • Pain • Rheumatology