Research area in which no drugs are currently approved
A disease-modifying osteoarthritis drug (DMOAD) is a disease-modifying drug that would inhibit or even reverse the progression of osteoarthritis.[1] Since the main hallmark of osteoarthritis is cartilage loss, a typical DMOAD would prevent the loss of cartilage and potentially regenerate it. Other DMOADs may attempt to help repair adjacent tissues by reducing inflammation.[2] A successful DMOAD would be expected to show an improvement in patient pain and function with an improvement of the health of the joint tissues.[3]
Approved for human use
There are currently no DMOADs approved for human use.[4]
23-amino acid peptide that induces articular cartilage formation [6] reduces pathological shape change of joint bones.[7]
In 2021 OrthoTrophix, the developer of the drug reported that one-year study of 93 patients suggested that TPX-100 treatment was associated with significant and sustained improvements in critical knee functions, preservation of knee cartilage thickness, reduced pathologic changes in underlying bone, and a >60% decrease in use of pain medications.[6] In late 2023, the company licensed TPX-100 to American Reagent in the US for an undisclosed amount.
p53/MDM2 inhibitor, induces apoptosis of senescent cells to create a favourable healing environment[22]
Phase 1 study complete in June 2019,[23] results were encouraging leading to plans for a phase 2 study. Phase 2 study results did not show any improvements and led to drug being discontinued from investigation.[24]
Phase 2 study completed in 2015,[27] with the company claiming that the data suggested the ability to prevent cartilage loss. As of 2024, the Ember Therapeutics website is down and Google suggests that the company is permanently closed.
Promote chondrogenesis through fibroblast growth factor receptor FGFR3[29]
Phase 2 study completed in 2017 and 5 year follow-up published in 2021,[30] demonstrated clear dose- and frequency-dependent improvements in cartilage thickness (primary endpoint), complete arrest in progression to joint replacement (in the high dose treatment groups), and improvements in the WOMAC pain survey for high-risk patients (secondary endpoint). Subsequent analysis additionally demonstrated statistically significant and clinically meaningful improvements in WOMAC progression for the high dose treatment groups relative to placebo.[31]
Phase 2 study completed in 2019, showing prevention of cartilage damage but did not show reduction in patient pain.[39]
Medivir
Invossa-K
(Transforming Growth Factor- β)
Cell/Gene therapy
Human studies halted by FDA for false ingredient claim.[40][41] There are claims FDA allowed for phase 3 trials to resume in the US.[42] As of January 2022, phase 3 clinical trial has resumed in the US.[43]
Note: Amniotic fluid is not a single drug and instead contains around 226 growth factors,[44] including BMP7.
Inflammation reducer[45] and cartilage growth enhancer.[46]
Initial 6 patient study in 2015 showed improvement in pain and function.[47] A randomised controlled trial of 200 patients completed in 2019,[48] also showing improved pain and function.
A 2019 non-randomised study in 20 patients showed improvement in joint tissue health.[49]
Pentosan Polysulfate Sodium (PPS) is a semi-synthetic drug manufactured from European beech xylans that are sulfated to produce a negatively charged product that mimics glycosaminoglycans (GAGs).
Paradigm's IND application to commence its phase 3 pivotal clinical trial investigating Pentosan Polysulphate Sodium (PPS) for the treatment of pain associated with knee osteoarthritis has been cleared by the US FDA.
Approximately 65 sites have been identified throughout the US and Australia. Contracting with many of those sites has been completed. The first 4 sites in Australia have initiated screening participants. Screening at the US sites is expected to begin prior to the end of CY2021.
The Company is now in a position to accelerate recruitment by adding approximately 10 sites in the United Kingdom (UK) and Europe, with site initiation and subject screening expected to commence in 1H CY 2022.[50][51][52]
Note: Cytonics offers autologous A2M therapy in humans but no randomised human trials have been published to date. A human trial is underway at NYU.[54]
Gene therapy for osteoarthritis is also being investigated as technology to create a drug that would act as a disease modifying drug. Several approved drugs are being investigated as repurposed agents in the treatment of osteoarthritis such as liraglutide (anti-diabetic and anti-obesity drug: NCT02905864), Metformin (anti-diabetic drug: NCT04767841, NCT05034029), Zoledronic acid (anti-osteoporotic drug: NCT04303026), etc.[4]
^Clinical trial number NCT03133676 for "A Study Evaluating the Safety, Pharmacokinetics, and Pharmacodynamics of KA34 in Subjects With Knee Osteoarthritis" at ClinicalTrials.gov
^Clinical trial number NCT02491281 for "First-in-human Single Ascending Dose Study of LNA043 in Patients Scheduled for Total Knee Replacement" at ClinicalTrials.gov
^Clinical trial number NCT03595618 for "A Study to Assess Efficacy and Safety of GLPG1972/S201086 in Patients With Knee Osteoarthritis" at ClinicalTrials.gov
^Conaghan PG, Bowes MA, Kingsbury SR, Brett A, Guillard G, Rizoska B, et al. (January 2020). "Disease-Modifying Effects of a Novel Cathepsin K Inhibitor in Osteoarthritis: A Randomized Controlled Trial". Annals of Internal Medicine. 172 (2): 86–95. doi:10.7326/M19-0675. PMID31887743. S2CID209518769.
^Clinical trial number NCT02705625 for "A Study to Evaluate the Efficacy, Safety and Tolerability of MIV-711 in Osteoarthritis Patients" at ClinicalTrials.gov
^Clinical trial number NCT03291470 for "A Randomized, Double-Blind, Placebo-Controlled, Multi-Center, Phase 3 Study to Determine the Efficacy and Safety of TG-C in Subjects With Kellgren and Lawrence Grade 2 or 3 Osteoarthritis of the Knee" at ClinicalTrials.gov
^Clinical trial number NCT03656575 for "Reduction of Pro-Inflammatory Synovial Fluid Biomarkers in Osteoarthritis of the Knee With Alpha-2 Macroglobulin" at ClinicalTrials.gov
^Carlson EL, Karuppagounder V, Pinamont WJ, Yoshioka NK, Ahmad A, Schott EM, et al. (February 2021). "Paroxetine-mediated GRK2 inhibition is a disease-modifying treatment for osteoarthritis". Science Translational Medicine. 13 (580). doi:10.1126/scitranslmed.aau8491. PMID33568523. S2CID231875553.