TPX-100 / OrthoTrophix, American Regent - LARVOL DELTA

OrthoTrophix Initiated Phase 2b Clinical Trial of TPX-100 in Patients with Mild to Severe Knee Osteoarthritis (PRNewswire) - "OrthoTrophix, Inc...today announced the initiation of a Phase 2b clinical trial of TPX-100, its lead therapeutic candidate, in patients with mild to severe knee osteoarthritis (OA) in the United States....The newly launched Phase 2b trial, titled 'A 53-Week Study Evaluating the Safety and Efficacy of Intra-Articular Injections of TPX-100 in Patients with Mild to Severe Tibiofemoral Osteoarthritis of the Knee,' is designed to confirm both the symptomatic improvements and structural effects observed in the earlier trial."

Trial status • Osteoarthritis

53-Week Study Evaluating the Safety and Efficacy of Intra-articular Injections of TPX-100 With Mild to Severe Tibio-Femoral Osteoarthritis of the Knee (clinicaltrials.gov) - P2 | N=270 | Recruiting | Sponsor: OrthoTrophix, Inc | Not yet recruiting ➔ Recruiting

Enrollment open • Immunology • Osteoarthritis • Pain • Rheumatology

53-Week Study Evaluating the Safety and Efficacy of Intra-articular Injections of TPX-100 with Mild to Severe Tibio-Femoral Osteoarthritis of the Knee (clinicaltrials.gov) - P2 | N=270 | Not yet recruiting | Sponsor: OrthoTrophix, Inc

New P2 trial • 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

TPX-100: OrthoTrophix Presents the Latest Clinical Data at BIO 2022 (PRNewswire) - "OrthoTrophix...announced today that the Company will present the latest clinical data and registration plan of TPX-100 in knee osteoarthritis (OA) patients at BIO 2022 (San Diego, CA for June 13 – 16)....'These data are persuasive that TPX-100 affects the critical pathophysiology of knee OA and that it results in striking clinical benefits to the patients,'..."

Clinical data • CNS Disorders • Osteoarthritis • Pain

INTRA-ARTICULAR TPX-100 SIGNIFICANTLY IMPROVES PAIN MEASURES AND SLOWS PATHOLOGICAL BONE SHAPE CHANGE IN KNEE OA (OARSI 2022) - "Study TPX-100-5 was designed to examine MRI-based 3-dimensional bone shape changes after IA TPX-100 or placebo in subjects with moderate to severe knee OA; and to investigate associations between bone shape changes and knee pain measures over 12 months. 3-D bone shape has been shown to predict OA onset, progression and total knee replacement, and has been demonstrated to be more responsive to change than conventional radiography."

Musculoskeletal Diseases • Musculoskeletal Pain • Orthopedics • Osteoarthritis • Pain

IMPROVED WOMAC PHYSICAL FUNCTION IS ASSOCIATED WITH SLOWED PATHOLOGICAL BONE SHAPE CHANGE AFTER TPX-100: TOWARDS A SURROGATE MARKER FOR VIRTUAL KNEE REPLACEMENT? (OARSI 2022) - "Structurally, MRI-based femoral bone shape (B-score) analysis also has been shown to predict TKR . The present study was designed to investigate bone-shape changes in subjects with MRI-confirmed, bilateral OA who had received IA TPX-100 or placebo; and to examine relationships, if any, between B-scores and WOMAC Physical Function scores in this population."

Musculoskeletal Diseases • Orthopedics • Pain

TPX-100: OrthoTrophix Presents New Data Suggesting Joint Bone Shape as a Possible Surrogate Marker for Virtual Joint Replacement in Knee Osteoarthritis (PRNewswire) - P2 | N=120 | TPX-100-5 (NCT01925261) | Sponsor: OrthoTrophix, Inc | "OrthoTrophix, Inc...announced today that the Company and its collaborators present clinical data strongly supporting joint bone shape change as part of a surrogate marker predictive of joint replacement in knee osteoarthritis (OA) patients....In the TPX-100-5, a Phase 2 study, placebo-treated knees with more advanced pathological joint bone shape change at baseline showed much faster progression of pathological bone shape change and poorer knee function at the end of the 12-month study period. In marked contrast, TPX-100-treated knees demonstrated reduction in pathological bone shape change and robust improvement of knee function through 12 months, regardless of severity at baseline. Consequently, both clinical (knee function) and structural (bone shape) efficacies of TPX-100 as compared to placebo were confirmed including in subjects with moderate to severe knee OA."

P2 data • CNS Disorders • Osteoarthritis • Pain

Study TPX-100-5: intra-articular TPX-100 significantly delays pathological bone shape change and stabilizes cartilage in moderate to severe bilateral knee OA. (PubMed, Arthritis Res Ther) - P2 | "This is the first report of a potential therapy demonstrating a significant effect on bone shape measured by B-score in knee OA. These data, in combination with previously reported statistically significant and clinically meaningful improvements in WOMAC physical function versus placebo, support TPX-100 as a candidate for disease modification in knee OA."

Journal • Immunology • Osteoarthritis • Pain • Rheumatology • MRI

TPX-100: OrthoTrophix presents more evidence for disease modification in knee osteoarthritis in a new abstract published in Osteoarthritis & Cartilage Journal (PRNewswire) - "OrthoTrophix, Inc....announced today that the Company has demonstrated more evidence for disease modification in knee osteoarthritis (OA) patients treated with TPX-100....In this study, three-dimensional (3D) shapes of the femur in knees of OA patients were measured with MRI at baseline (before treatment) and 6 and 12 months after treatment....'Our clinical data suggest that reducing pathological femoral bone shape change and stabilizing knee cartilage go hand in hand with functional improvements for patients....These data provide further support for TPX-100 as a disease modifying drug for knee OA.'"

Clinical data • CNS Disorders • Immunology • Inflammation • Osteoarthritis • Pain • Rheumatology

TPX-100: OrthoTrophix demonstrates evidence for disease modification in knee osteoarthritis (PRNewswire) - P2, N=120; NCT01925261; Sponsor: OrthoTrophix; "OrthoTrophix...announced today that the Company has demonstrated evidence for disease modification in knee osteoarthritis (OA) in patients treated with TPX-100, the Company's leading candidate for a Disease Modifying Osteoarthritis Drug (DMOAD)....TPX-100-treated knees demonstrated clinically meaningful and statistically significant improvement in critical knee functions, based on 17 measures, as compared to placebo-treated knees by 6 months, with benefits maintained through 12 months."

P2 data

Stabilization of Patellar Bone-Shape Correlates Significantly with Reduced Knee Pain Frequency After IA TPX-100 in Subjects with Bilateral Patellofemoral OA (ACR-ARHP 2019) - "In subjects with MRI-confirmed bilateral PFOA, a single series of IA TPX-100 is associated with statistically significant and clinically meaningful reductions in knee pain frequency at 12 months, significantly correlated with reduced or stabilized pathologic patellar bone shape change compared with placebo. Quartile analysis suggests a “dose-response” relationship between reduced patellar bone shape change and reduced knee pain frequency in TPX-100-treated knees. These concordant structural and symptomatic benefits support development of TPX-100 as a candidate DMOAD as well as further study of bone shape change as an imaging biomarker in knee OA."

Clinical

Intra-Articular TPX-100 Significantly Delays Pathological Bone Shape Change at 6 and 12 Months in Moderate to Severe Tibiofemoral OA (ACR-ARHP 2019) - "Femoral bone shape change is progressive in normal aging and is accelerated in knee OA. Increasing change predicts worsening of symptomatic and radiographic knee OA and joint failure. After a single, 4-injection series (200 mg/injection), TPX-100 treatment in subjects with moderate to severe TFOA was associated with significantly slowed pathological femoral bone-shape change at 6 and 12 months compared with placebo."

OrthoTrophix presents evidence for disease modification in knee osteoarthritis by TPX-100 at American College of Rheumatology Annual Meeting (Businesswire) - "OrthoTrophix, Inc....announced today that TPX-100 treatment is associated with significant decreases in MRI-based structural pathology in knee OA compared with placebo. These results, from a randomized, double-blind, placebo-controlled Phase 2 trial, correlate significantly with striking improvements in patient reported clinical benefits. The data are presented in two posters at the American College of Rheumatology (ACR/ARP) Annual Meeting in Atlanta, GA."

P2 data

OrthoTrophix presents clinical data at European Congress of Rheumatology demonstrating significant correlation between knee function improvement and cartilage thickness increase/stabilization after TPX-100 (Businesswire) - P2, N=120; NCT01925261; Sponsor: OrthoTrophix, Inc; “OrthoTrophix, Inc...announced today that the company and its collaborators are presenting Phase 2 clinical study data at the European Congress of Rheumatology in Madrid, Spain (June 12 – 15)....Knee function...at 6 and 12 months, was markedly improved in TPX-100-treated knees compared to placebo-exposed knees.”

P2 data

Reduction in pathological bone shape change correlates with decreased frequency of knee pain after TPX-100 treatment (Businesswire) - "OrthoTrophix, Inc....announced today new results from a Phase 2 study of the osteoarthritis drug TPX-100....'The reduction in pain frequency after TPX-100 was robust and sustained in over 50% of knees treated with TPX-100: from 'daily' to less than weekly at 12 months.'"

P2 data

IMPROVED KNEE PHYSICAL FUNCTION CORRELATES SIGNIFICANTLY WITH TIBIOFEMORAL CARTILAGE THICKNESS INCREASE AFTER IA TPX-100: RESULTS OF A POST HOC ANALYSIS (EULAR 2019) - "In subjects with bilateral TFOA, statistically significant and clinically meaningful, robust functional improvements in TPX-100-treated knees were seen at 6 and 12 months compared with placebo-exposed knees. Formal analysis revealed statistically significant correlations between functional improvement and increase or stabilization of lateral, medial and total TF cartilage thickness. To our knowledge, TPX-100 is the first candidate DMOAD to show improvement in critical knee function concordant with increase/stabilization of cartilage structure compared with placebo-exposed knees."

Retrospective data