MIV-711 / Medivir - LARVOL DELTA

Medivir AB announced that its selective cathepsin K inhibitor, MIV-711, has been granted Orphan Drug Designation by the FDA for the treatment of Osteogenesis Imperfecta (OI), a rare genetic disorder affecting bone fragility. (TipRanks)

Orphan drug • Rare Diseases

Cathepsin K (CTSK) in Inflammatory and Immune-Mediated Diseases. (PubMed, Immunol Invest) - "Small-molecule inhibitors (odanacatib, MIV-711, ONO-5334) and biologics attenuate pathology in arthritis, periodontitis, and atherosclerosis. CTSK is a promising diagnostic biomarker and therapeutic target, yet its promise hinges on inhibitors that act only where needed, sparing other tissues. Next steps must therefore craft more selective allosteric compounds and test ways to confine them to diseased sites."

Journal • Review • Atherosclerosis • Cardiovascular • Dental Disorders • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Arthritis • Inflammatory Bowel Disease • Oncology • Periodontitis • Rheumatoid Arthritis • Rheumatology • CTSK

Assessment of Differential Treatment Effect Between Predicted Endotype Subgroups of Knee Osteoarthritis in the MIV-711, UBX0101, and Oral Salmon Calcitonin Trials (EULAR 2025) - P2, P2a, P3 | "This study demonstrates the potential to predict OA endotypes using a small, targeted panel of biomarkers on trial data, offering a clinically practical tool to enhance trial recruitment. The observed responses to anti-resorptive treatments within OA subgroups highlight the potential benefits of aligning therapies with endotypes defined by the drug’s mode of action. Further investigation is needed to refine strategies for recruiting the right subgroups at the optimal time."

Immunology • Musculoskeletal Pain • Osteoarthritis • Pain • Rheumatology • CTSK

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

Synthesis and Biological Evaluation of Novel Piperidine-3-Carboxamide Derivatives as Anti-Osteoporosis Agents Targeting Cathepsin K. (PubMed, Molecules) - "Molecular docking studies revealed that H-9 formed several hydrogen bonds and hydrophobic interactions with key active-site residues of cathepsin K. In vitro, H-9 demonstrated anti-bone resorption effects that were comparable to those of MIV-711, a cathepsin K inhibitor currently in phase 2a clinical trials for the treatment of bone metabolic disease...Moreover, in vivo experiments showed that H-9 increased the bone mineral density of OVX-induced osteoporosis mice. These results suggest that H-9 is a potent anti-bone resorption agent targeting cathepsin K and warrants further investigation for its potential anti-osteoporosis values."

Journal • Metabolic Disorders • Osteoporosis • Rheumatology • CTSK • TNFSF11

Symptomatic and structural benefit of cathepsin K inhibition by MIV-711 in a subgroup with unilateral pain: post-hoc analysis of a randomised phase 2a clinical trial. (PubMed, Clin Exp Rheumatol) - "In a subgroup with predominantly unilateral knee pain, significant reduction in OA pain by MIV-711 100 mg treatment was found, with concurrent beneficial structural effects, highlighting the importance of appropriate pain inclusion criteria in OA trials."

Journal • P2a data • Retrospective data • Immunology • Musculoskeletal Pain • Osteoarthritis • Pain • Rheumatology • CTSK

A subgroup analysis of Medivir´s phase II study of MIV-711 for osteoarthritis shows statistically significant reduction in OA pain (PRNewswire) - "Medivir AB...today announces that an article entitled 'Symptomatic and structural benefit of cathepsin K inhibition by MIV-711 in a subgroup with unilateral pain: post-hoc analysis of a randomised phase 2a clinical trial' by Bihlet, A.R. et al has been published in Clinical and Experimental Rheumatology 2022...This exploratory analysis focused on a subgroup of patients in the MIV-711 phase IIa trial with pain predominantly in one knee (unilateral pain). In a subgroup with predominantly unilateral knee pain, a statistically significant reduction in OA pain by MIV-711 treatment was found, with concurrent beneficial structural effects."

P2 data • Retrospective data • CNS Disorders • Osteoarthritis • Pain

"Subgruppsanalys av Medivirs fas II-studie med MIV-711 mot artros visar signifikant minskad artrosrelaterad smärta https://t.co/1o2AY9uckq" (@CisionNews)

Medivir AB - Interim Report January - September 2021 (PRNewswire) - "Medivir has two more drug development projects in the clinical development phase, remetinostat, and MIV-711. Medivir does not conduct clinical development of these projects on its own, but instead seeks partners for further development."

Licensing / partnership • CNS Disorders • Osteoarthritis • Pain

Inhibitory effect of cathepsin K inhibitor (ODN-MK-0822) on invasion, migration and adhesion of human breast cancer cells in vitro. (PubMed, Mol Biol Rep) - "Previous studies on the role of cathepsin K (CTSK) in metastatic spreading led to several strategies for inhibition of this molecule such as MIV-711 (Medivir), balicatib and odanacatib (ODN) which were on trial in the past. ODN exerts anti-metastatic action through inhibition of signaling pathway for MMP-9, PI3K and MAPK. This indicates potential therapeutic effects of ODN in the treatment of metastatic breast cancer."

Journal • Preclinical • Breast Cancer • Oncology • Solid Tumor • MAPK8 • MMP9 • PXN • RAC1 • TIMP1

Disease-Modifying Effects of a Novel Cathepsin K Inhibitor in Osteoarthritis: A Randomized, Placebo-Controlled Study. (PubMed, Ann Intern Med) - P2, P2a | "MIV-711 is a novel selective cathepsin K inhibitor with beneficial effects on bone and cartilage in preclinical osteoarthritis models...This treatment may merit further evaluation as a disease-modifying osteoarthritis drug. Medivir."

Clinical • Journal • Immunology • Osteoarthritis • Pain • Rheumatology

A Study to Evaluate Safety and Tolerability of MIV-711 in Osteoarthritis Patients (clinicaltrials.gov) - P2; N=50; Active, not recruiting; Sponsor: Medivir; Recruiting ➔ Active, not recruiting; N=80 ➔ 50

Enrollment change • Enrollment closed • Biosimilar • CNS Disorders • Demo Pain • Immunology • Inflammation • Osteoarthritis • Pain

Medivir AB - Interim report January - March 2020 (PRNewswire) - "Significant events during the quarter:...The phase II study with MIV-711 in patients with osteoarthritis was published in the esteemed journal Annals of Internal Medicine."

P2 data • CNS Disorders • Immunology • Inflammation • Osteoarthritis • Pain • Rheumatology

The selective cathepsin K inhibitor MIV-711 attenuates joint pathology in experimental animal models of osteoarthritis. (PubMed, J Transl Med) - "MIV-711 prevents subchondral bone loss and partially attenuates cartilage pathology in two animal models of OA. These beneficial effects of MIV-711 on joint pathology are observed in conjunction with decreases in bone and cartilage biomarkers that have been shown to be clinically attainable in human. The data support the further development of MIV-711 for the treatment of OA."

Biomarker • Journal • Preclinical

Nonclinical and clinical pharmacological characterization of the potent and selective cathepsin K inhibitor MIV-711. (PubMed, J Transl Med) - "MIV-711 is a potent and selective cathepsin K inhibitor with dose-dependent effects on biomarkers of bone and cartilage degradation in monkey and human. Taken together, MIV-711 shows promise for the treatment of bone and cartilage related disorders in humans, such as OA. Trial Registration EudraCT number 2011-003024-12, registered on June 22nd 2011."

Biomarker • Clinical • Journal

Data from the MIV-711 phase II program to be presented at the OARSI World Congress (PRNewswire) - "Medivir AB...today informs that new data from the phase II program of MIV-711, will be presented during the Osteoarthritis Research Society International (OARSI) world congress, which will take place 2-5 May in Toronto, Canada. Data from the six months' open label extension study of MIV-711 in patients with osteoarthritis will be presented."

P2 data

SAFETY AND EFFICACY OF SIX MONTHS´ OPEN LABEL EXTENSION POST-RCT USING THE NOVEL CATHEPSIN K INHIBITOR MIV-711 IN PATIENTS WITH KNEE OSTEOARTHRITIS (OARSI 2019) - "This study demonstrated that MIV-711 has acceptable safety and tolerability in knee OA patients, with the overall safety profile in patients completing 12 months´ of treatment similar to that seen in the placebo-controlled study. The beneficial effects on both bone and cartilage measures as well as symptom measures that were seen in the placebo-controlled study were maintained during the second 6-month treatment period, although results must be interpreted with caution as this was an uncontrolled extension study with a limited number of patients. Based on these results, progression of MIV-711 into pivotal studies as a DMOAD is therefore warranted."

Clinical

2020 OA Vision: Emerging Therapeutics on the OA Landscape (OARSI 2019) - "...In terms of existing therapies and pain control, a novel microsphere-based delivery system has enabled the development of a triamcinolone acetonide-extended release formulation for intra-articular (IA) delivery, providing sustained IA presence...Hydroxychloroquine was not effective in 2 large hand OA trials, while the results of methotrexate are presented elsewhere at this meeting...Results from an anti-interleukin1alpha/beta dual variable domain immunoglobulin (ABT-981) were however disappointing, with limited effects on pain and no benefits on MRI-assessed synovitis, in both knee and hand OA...Positive data from new phIII trials is now emerging, including use of a subcutaneous formulation of tanezumab...Sprifermin is a recombinant human fibroblast growth factor 18 given IA that promotes chondrocyte growth, and recent long-term results from a phII RCT suggest improvements in cartilage thickness with the active therapy, though no benefits above placebo for pain. Ph II..."