Clinical Trials

Phase 3: Extension Study Evaluating the Safety and Efficacy of a Second Year of Use of Lorecivivint in Subjects With Osteoarthritis of the Knee

Phase 3: A Study Utilizing Patient-Reported Outcomes to Evaluate the Safety and Efficacy of Lorecivivint (SM04690) for the Treatment of Moderately to Severely Symptomatic Knee Osteoarthritis (STRIDES-1)

Phase 3: A Phase 3 Study Utilizing Patient-Reported and Radiographic Outcomes and Evaluating the Safety and Efficacy of Lorecivivint (SM04690) for the Treatment of Moderately to Severely Symptomatic Knee Osteoarthritis (STRIDES-X-ray)

Phase 2: A Study Evaluating the Safety, Tolerability and Efficacy of Two Injections of SM04690 for the Treatment of Moderately to Severely Symptomatic Knee Osteoarthritis

Phase 2: A Study Utilizing Imaging Techniques and Evaluating the Safety and Efficacy of SM04690 for the Treatment of Moderately to Severely Symptomatic Knee Osteoarthritis

Phase 2: An Observational Study Evaluating the Safety, Tolerability, and Efficacy of Treatment of SM04690 or Placebo Previously Injected in the Target Knee Joint of Subjects With Moderately to Severely Symptomatic Osteoarthritis 

Phase 2: A Study Evaluating the Safety and Efficacy of SM04690 for the Treatment of Moderately to Severely Symptomatic Knee Osteoarthritis 

Phase 2: A Study Evaluating the Safety, Tolerability, and Efficacy of SM04690 Injected in the Target Knee Joint of Moderately to Severely Symptomatic Osteoarthritis Subjects 

Phase 1: Drug-Drug Interaction Study of Lorecivivint and Triamcinolone Acetonide in Healthy Volunteers

Phase 1: Phase 1, Dose Escalation Study Evaluating the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of SM04690 in Moderate to Severe Knee Osteoarthritis (OA)

Corporate Memberships and Collaborations

ORBIT Registry (Brigham and Women’s Hospital)

Samumed is sponsoring the Osteoarthritis Registry of Biomarker and Imaging Trajectories (ORBIT). The data from this study will enhance our understanding of the natural history of knee osteoarthritis. This registry was developed in collaboration with investigators at Brigham and Women’s Hospital at Harvard Medical School.

PROGRESS OA (Foundation for the National Institutes of Health (FNIH) Biomarkers Consortium)

Samumed is a partner on the FNIH Biomarkers Consortium’s PROGRESS OA Project: Clinical Evaluation and Qualification of Osteoarthritis Biomarkers. The project seeks to qualify imaging and biochemical biomarkers with the FDA as prognostic biomarkers of disease progression in knee osteoarthritis.

Osteoarthritis Research Society International (OARSI)

Samumed is proud to be a Corporate Member of OARSI, the leading medical society for advancing the understanding, early detection, treatment, and prevention of osteoarthritis through its exclusive dedication to research. OARSI is the only organization that is exclusively dedicated to advancing osteoarthritis research.

International Cartilage Regeneration & Joint Preservation Society (ICRS)

Samumed is proud to be a Corporate Member of the ICRS, the main forum for international collaboration in cartilaginous tissue research and joint preservation. The ICRS seeks to improve patients’ quality of life, decrease their disability, and reduce the impact of degenerative joint disease on healthcare systems worldwide.

Early OA Consortium (KU Leuven)

Samumed is providing financial support to an international consortium led by Prof. Frank P. Luyten (KU Leuven, BE) and Prof. S. Lohmander (Lund, SWE) in their initiative to develop and validate classification criteria for early-stage osteoarthritis (OA) of the knee. This task force aims to define the patient with early knee OA and is considered a critical contribution to ongoing efforts in the field of OA for patient stratification, proposing early disease as a window of opportunity to better understand the disease process, reduce the burden of OA disease, and potentially prevent disease progression. This initiative is interdisciplinary, connecting the work of basic researchers, physician scientists, and clinicians and aims to go across continents and professional disciplines including general practitioners, rheumatologists, orthopedic surgeons, and physiotherapists, while also involving patient organizations.

STEpUP OA (Oxford University)

Samumed is pleased to support Synovial fluid To define molecular EndotyPes by Unbiased Proteomics in OA (STEpUP OA), an Oxford University-led effort, which has created a partnership to characterize the synovial fluid protein signatures of osteoarthritis patients. Data generated as part of this endeavor may potentially guide clinical decision-making by allowing for better characterization of osteoarthritis disease stages and risk of progression.

Publications

Osteoarthritis and Cartilage | February 12, 2021

  • A Phase 2b Randomized Trial of Lorecivivint, a Novel Intra-articular CLK2/DYRK1A Inhibitor and Wnt Pathway Modulator for Knee Osteoarthritis

    Osteoarthritis and Cartilage. doi: 10.1016/j.joca.2021.02.004


    Yusuf Yazici, MD, Timothy E. McAlindon, MD, MPH, Allan Gibofsky, MD, JD, Nancy E. Lane, MD, Christian Lattermann, MD, Nebojsa Skrepnik, MD, PhD, Christopher J. Swearingen, PhD, Ismail Simsek, MD, Heli Ghandehari, MS, Anita DiFrancesco, BS, BA, Jamielle Gibbs, MPH, Jeyanesh Tambiah, MD, Marc C. Hochberg, MD, MPH

American College of Rheumatology (ACR) Convergence | November 02 - 05, 2020

Journal of Medical Economics | August 13, 2020

  • Health care resource utilization and burden of disease in a U.S. Medicare population with a principal diagnosis of osteoarthritis of the knee

    Journal of Medical Economics. doi: 10.1080/13696998.2020.1801453


    Fang Chen, Wenqing Su, Angela V. Bedenbaugh & Arman Oruc

Arthritis & Rheumatology | May 20, 2020

  • Lorecivivint, a Novel Intraarticular CDC‐like Kinase 2 and Dual‐Specificity Tyrosine Phosphorylation‐Regulated Kinase 1A Inhibitor and Wnt Pathway Modulator for the Treatment of Knee Osteoarthritis: A Phase II Randomized Trial

    Arthritis & Rheumatology. doi: 10.1002/art.41315


    Yusuf Yazici, Timothy E. McAlindon, Allan Gibofsky, Nancy E. Lane, Daniel Clauw, Morgan Jones, John Bergfeld, Christopher J. Swearingen, Anita DiFrancesco, Ismail Simsek, Jeyanesh Tambiah, Marc C. Hochberg

Cartilage Regeneration & Joint Preservation Society (ICRS) World Congress | October 05 - 08, 2019

Cartilage Regeneration & Joint Preservation Society (ICRS) World Congress | October 05 - 08, 2019

Gordon Research Conference (GRC) - Wnt Signaling Networks in Development, Disease and Regeneration | August 11 - 16, 2019

Osteoarthritis and Cartilage | May 24, 2019

  • Modulation of the Wnt pathway through inhibition of CLK2 and DYRK1A by lorecivivint as a novel, potentially disease-modifying approach for knee osteoarthritis treatment

    Osteoarthritis and Cartilage. doi: 10.1016/j.joca.2019.05.006


    V. Deshmukh, A.L. O'Green, C. Bossard, T. Seo, L. Lamangan, M. Ibanez, A. Ghias, C. Lai, L. Do, S. Cho, J. Cahiwat, K. Chiu, M. Pedraza, S. Anderson, R. Harris, L. Dellamary, S. KC, C. Barroga, B. Melchior, B. Tam, S. Kennedy, J. Tambiah, J. Hood, Y. Yazici

International Society for Pharmaeconomics and Outcomes Research (ISPOR) | May 18 - 22, 2019

International Cartilage Regeneration & Joint Preservation Society (ICRS) Summit | January 17 - 18, 2019

World Congress on Osteoporosis, Osteoarthritis, and Musculoskeletal Diseases | April 19 - 22, 2018

World Congress on Osteoporosis, Osteoarthritis, and Musculoskeletal Diseases | April 19 - 22, 2018

Osteoarthritis and Cartilage | September 15, 2017

Osteoarthritis and Cartilage | July 13, 2017

  • A novel Wnt pathway inhibitor, SM04690, for the treatment of moderate to severe osteoarthritis of the knee: results of a 24-week, randomized, controlled, phase 1 study

    Osteoarthritis and Cartilage, 25(10), 1598-1606. doi: 10.1016/j.joca.2017.07.006


    Y. Yazici, T.E. McAlindon, R. Fleischmann, A. Gibofsky, N.E. Lane, A.J. Kivitz, N. Skrepnik, E. Armas, C.J. Swearingen, A. DiFrancesco, J.R.S. Tambiah, J. Hood, M.C. Hochberg

International Cartilage Repair Society Heritage Summit | June 29 - July 01, 2017

International Society for Pharmacoeconomics and Outcomes (ISPOR) | May 20 - 24, 2017

Award Winning

Osteoarthritis of the Knee

Arthritis is the most common cause of disability among adults, and osteoarthritis (OA) is the most common type of arthritis, accounting for much of this burden.1

  • The global prevalence of symptomatic knee OA has been estimated at 3.8% (4.8% for females and 2.8% for males).2
  • Current estimates indicate that there are 14 million U.S. adults with symptomatic knee osteoarthritis.3 The overall number of U.S. adults affected by OA in any joint has increased during recent decades and is estimated to affect 30 million U.S. adults today, primarily due to an aging population and an ever-increasing prevalence of obesity.1
  • The combination of direct medical costs, pain and suffering, and loss of workplace productivity elevates OA to a major socioeconomic problem for health systems, the economy, and suffering patients.4

OA is characterized by the destruction of articular cartilage and structural changes in bone, which contribute to pain and loss of joint function.5 The Wnt signaling pathway plays a central role in the processes that direct the lineage fate of stem cells, that are resident in the joint, toward bone (osteoblasts) or cartilage (chondrocytes).6,7

  • In OA joints, elevated Wnt activity has been shown to cause these stem cells to become osteoblasts instead of chondrocytes and to lead to the production of proteases that degrade cartilage.8,9,10
  • Inhibition of Wnt signaling in OA joints may drive stem cells to become chondrocytes and block protease-mediated cartilage degradation, resulting in cartilage regeneration.8,11
  • Therapies that target the Wnt pathway may therefore have potential in treating OA.8

References

    1. Centers for Disease Control and Prevention. Osteoarthritis. Available at https://www.cdc.gov/arthritis/basics/osteoarthritis.htm.
    2. Cross M, Smith E, Hoy D, et al. The global burden of hip and knee osteoarthritis: estimates from the global burden of disease 2010 study. Ann Rheum Dis. 2014;73(7):1323-30.
    3. Deshpande BR, Katz JN, Solomon DH, et al. Number of persons with symptomatic knee osteoarthritis in the US: impact of race and ethnicity, age, sex, and obesity. Arthritis Care Res (Hoboken). 2016;68(12):1743-50.
    4. Wier LM, Levit K, Stranges E, et al. HCUP facts and figures: statistics on hospital based care in the United States, 2008. Rockville, MD: Agency for Healthcare Research and Quality, 2010. Available at http://www.hcup-us.ahrq.gov/reports/factsandfigures/2008/pdfs/FF_report_2008.pdf.
    5. Glyn-Jones S, Palmer AJR, Agricola R, et al. Osteoarthritis. Lancet. 2015;386(9991):376-87.
    6. Clevers H, Loh KM, Nusse R. Stem cell signaling. An integral program for tissue renewal and regeneration: Wnt signaling and stem cell control. Science. 2014;346(6205):1248012.
    7. Blom AB, Brockbank SM, Van Lent PL, et al. Involvement of the Wnt signaling pathway in experimental and human osteoarthritis: prominent role of Wnt-induced signaling protein 1. Arthritis Rheum. 2009;60(2):501-12.
    8. Monteagudo S, Lories RJ. Cushioning the cartilage: a canonical Wnt restricting matter. Nat Rev Rheumatol. 2017;13(11):670-81.
    9. Gelse K, Ekici AB, Cipa F, et al. Molecular differentiation between osteophytic and articular cartilage – clues for a transient and permanent chondrocyte phenotype. Osteoarthritis Cartilage. 2012;20(2):162-71.
    10. Corr M. Wnt-beta-catenin signaling in the pathogenesis of osteoarthritis. Nat Clin Pract Rheumatol. 2008;4(10):550-6.
    11. Zimmerman ZF, Moon RT, Chien AJ. Targeting Wnt pathways in disease. Cold Spring Harb Perspect Biol. 2012;4(11):a008086.