LNA043 / Novartis - LARVOL DELTA

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

ONWARDS: Study of Efficacy, Safety, and Tolerability of LNA043 in Patients With Knee Osteoarthritis (clinicaltrials.gov) - P2 | N=583 | Active, not recruiting | Sponsor: Novartis Pharmaceuticals | Trial completion date: Oct 2027 ➔ May 2025

Trial completion date • Immunology • Osteoarthritis • Pain • Rheumatology

A Safety and Efficacy Study of Anti-inflammatory (Canakinumab) and Cartilage Stimulating (LNA043) Drugs Injected Into the Knee Joint of Participants With Knee Osteoarthritis (OA) (clinicaltrials.gov) - P2 | N=23 | Terminated | Sponsor: Novartis Pharmaceuticals | Completed ➔ Terminated; Sponsor Decision

Trial termination • Immunology • Osteoarthritis • Pain • Rheumatology • CRP

A Safety and Efficacy Study of Anti-inflammatory (Canakinumab) and Cartilage Stimulating (LNA043) Drugs Injected Into the Knee Joint of Participants With Knee Osteoarthritis (OA) (clinicaltrials.gov) - P2 | N=23 | Completed | Sponsor: Novartis Pharmaceuticals | Active, not recruiting ➔ Completed

Trial completion • Immunology • Osteoarthritis • Pain • Rheumatology • CRP

Defining a 'valid' measurement and test-retest reliability of actigraphy based digital endpoints of physical activity in knee osteoarthritis (OARSI 2024) - P2 | "But evidence is required to show that these are fit for purpose within the context of knee OA. The analysis presented here uses blinded, pre-treatment data from a Phase IIb randomised controlled trial of LNA043 in knee OA (ONWARDS; NCT04864392) to support the definition of 'valid' digitally-derived physical activity (DDPA) endpoints, and evaluate their test-retest reliability."

Immunology • Osteoarthritis • Pain • Rheumatology

A Safety and Efficacy Study of Anti-inflammatory (Canakinumab) and Cartilage Stimulating (LNA043) Drugs Injected Into the Knee Joint of Participants With Knee Osteoarthritis (OA) (clinicaltrials.gov) - P2 | N=24 | Active, not recruiting | Sponsor: Novartis Pharmaceuticals | Recruiting ➔ Active, not recruiting | N=138 ➔ 24

Enrollment change • Enrollment closed • Immunology • Osteoarthritis • Pain • Rheumatology • CRP

A Safety and Efficacy Study of Anti-inflammatory (Canakinumab) and Cartilage Stimulating (LNA043) Drugs Injected Into the Knee Joint of Participants With Knee Osteoarthritis (OA) (clinicaltrials.gov) - P2 | N=138 | Recruiting | Sponsor: Novartis Pharmaceuticals | Trial completion date: Oct 2025 ➔ Jun 2024 | Trial primary completion date: Oct 2025 ➔ Jun 2024

Trial completion date • Trial primary completion date • Immunology • Osteoarthritis • Pain • Rheumatology • CRP

ONWARDS: Study of Efficacy, Safety, and Tolerability of LNA043 in Patients With Knee Osteoarthritis (clinicaltrials.gov) - P2 | N=550 | Recruiting | Sponsor: Novartis Pharmaceuticals | Active, not recruiting ➔ Recruiting

Enrollment open • Immunology • Osteoarthritis • Pain • Rheumatology

A Safety and Efficacy Study of Anti-inflammatory (Canakinumab) and Cartilage Stimulating (LNA043) Drugs Injected Into the Knee Joint of Participants With Knee Osteoarthritis (OA) (clinicaltrials.gov) - P2 | N=138 | Recruiting | Sponsor: Novartis Pharmaceuticals | Trial completion date: Apr 2025 ➔ Oct 2025 | Trial primary completion date: Apr 2025 ➔ Oct 2025

Trial completion date • Trial primary completion date • Immunology • Osteoarthritis • Pain • Rheumatology • CRP

ONWARDS: Study of Efficacy, Safety, and Tolerability of LNA043 in Patients With Knee Osteoarthritis (clinicaltrials.gov) - P2 | N=581 | Active, not recruiting | Sponsor: Novartis Pharmaceuticals | Recruiting ➔ Active, not recruiting

Enrollment closed • Immunology • Osteoarthritis • Pain • Rheumatology

Angiopoietin-like 3-derivative LNA043 for cartilage regeneration in osteoarthritis: a randomized phase 1 trial. (PubMed, Nat Med) - P1, P2 | "Post-hoc transcriptomics profiling of cartilage revealed that a single LNA043 injection reverses the OA transcriptome signature over at least 21 d, inducing the expression of hyaline cartilage matrix components and anabolic signaling pathways, while suppressing mediators of OA progression. LNA043 is a novel disease-modifying OA drug candidate that is currently in a phase 2b trial ( NCT04864392 ) in patients with knee OA."

Clinical • Journal • P1 data • Immunology • Musculoskeletal Diseases • Orthopedics • Osteoarthritis • Pain • Rheumatology • FN1

A Safety and Efficacy Study of Anti-inflammatory (Canakinumab) and Cartilage Stimulating (LNA043) Drugs Injected Into the Knee Joint of Participants With Knee Osteoarthritis (OA) (clinicaltrials.gov) - P2 | N=138 | Recruiting | Sponsor: Novartis Pharmaceuticals | Trial completion date: Apr 2024 ➔ Apr 2025 | Trial primary completion date: Apr 2024 ➔ Apr 2025

Trial completion date • Trial primary completion date • Immunology • Osteoarthritis • Pain • Rheumatology • CRP

Study of Safety, Tolerability, Preliminary Efficacy of Intra-articular LNA043 Injections in Patients With Articular Cartilage Lesions and Knee Osteoarthritis. (clinicaltrials.gov) - P2 | N=142 | Completed | Sponsor: Novartis Pharmaceuticals | Active, not recruiting ➔ Completed

Trial completion • Immunology • Osteoarthritis • Pain • Rheumatology

CARTILAGE REGENERATION AFTER TREATMENT WITH LNA043, A NOVEL DISEASE-MODIFYING OSTEOARTHRITIS DRUG CANDIDATE: RESULTS FROM AN IMAGING-BASED PROOF-OF-CONCEPT TRIAL IN PATIENTS WITH FOCAL ARTICULAR CARTILAGE LESIONS IN THE KNEE (OARSI 2022) - P2 | "A previous proof-of-mechanism study focussed on imaging using 7 Tesla magnetic resonance imaging (MRI) to show the formation of hyaline-like tissue after a single injection of 20 mg LNA04. The aim of this study is to non-invasively evaluate the chondro-regenerative capacity of multiple intra-articular (i.a.) injections of LNA043 in patients with articular cartilage lesions in the knee (NCT03275064)."

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

LNA043 A NOVEL CANDIDATE FOR OSTEOARTHRITIS TREATMENT INDUCES CARTILAGE REGENERATION AND REVERSES THE OSTEOARTHRITIS TRANSCRIPTOME (OARSI 2022) - "Using a phenotypic screen, we discovered LNA043, a derivative of the angiopoietin-like 3 (ANGPTL3) protein and confirmed that it promotes chondrogenesis in vitro and cartilage regeneration in vivo. The mechanisms-of-action (MoA) of LNA043 was characterized by a transcriptomics analysis of OA cartilage from LNA043-treated patients and by mechanistic molecular assays."

Immunology • Osteoarthritis • Pain • Rheumatology

A Safety and Efficacy Study of Anti-inflammatory (Canakinumab) and Cartilage Stimulating (LNA043) Drugs Injected Into the Knee Joint of Participants With Knee Osteoarthritis (OA) (clinicaltrials.gov) - P2 | N=138 | Recruiting | Sponsor: Novartis Pharmaceuticals | Trial completion date: Dec 2023 ➔ Apr 2024 | Initiation date: Jan 2021 ➔ Aug 2021 | Trial primary completion date: Dec 2023 ➔ Apr 2024

Trial completion date • Trial initiation date • Trial primary completion date • Immunology • Osteoarthritis • Pain • Rheumatology • CRP

A Safety and Efficacy Study of Anti-inflammatory (Canakinumab) and Cartilage Stimulating (LNA043) Drugs Injected Into the Knee Joint of Participants With Knee Osteoarthritis (OA) (clinicaltrials.gov) - P2 | N=138 | Recruiting | Sponsor: Novartis Pharmaceuticals | Trial completion date: May 2024 ➔ Dec 2023 | Trial primary completion date: May 2024 ➔ Dec 2023

Trial completion date • Trial primary completion date • Immunology • Osteoarthritis • Pain • Rheumatology • CRP

ONWARDS: Study of Efficacy, Safety, and Tolerability of LNA043 in Patients With Knee Osteoarthritis (clinicaltrials.gov) - P2 | N=550 | Recruiting | Sponsor: Novartis Pharmaceuticals | Trial completion date: Jun 2027 ➔ Oct 2027 | Trial primary completion date: Jun 2024 ➔ Nov 2024

Trial completion date • Trial primary completion date • Immunology • Osteoarthritis • Pain • Rheumatology

A Safety and Efficacy Study of Anti-inflammatory (Canakinumab) and Cartilage Stimulating (LNA043) Drugs Injected Into the Knee Joint of Participants With Knee Osteoarthritis (OA) (clinicaltrials.gov) - P2 | N=138 | Recruiting | Sponsor: Novartis Pharmaceuticals | Initiation date: Aug 2021 ➔ Jan 2021

Trial initiation date • Immunology • Osteoarthritis • Pain • Rheumatology • CRP • MRI

Study of Safety, Tolerability, Preliminary Efficacy of Intra-articular LNA043 Injections in Patients With Articular Cartilage Lesions and Knee Osteoarthritis. (clinicaltrials.gov) - P2; N=142; Active, not recruiting; Sponsor: Novartis Pharmaceuticals; Recruiting ➔ Active, not recruiting

Clinical • Enrollment closed • Immunology • Osteoarthritis • Pain • Rheumatology • MRI

"هيئة الغذاء والدواء تمنح مشروع الدواء 💉LNA043 صفة الاستعجال في مجال التهاب المفاصل (الركبة) ✅نتائج أولية من نوفارتيس @Novartis بينت بوادر تحفيز ترميم الغضروف بالحقن في المفصل https://t.co/hadxFWZIpt 🗓متوقع إجراء التجارب الإكلينيكية المرحلة الثانية قريبا https://t.co/dTKdOmSGec" (@YAYshamsaldeen)

A Safety and Efficacy Study of Anti-inflammatory (Canakinumab) and Cartilage Stimulating (LNA043) Drugs Injected Into the Knee Joint of Participants With Knee Osteoarthritis (OA) (clinicaltrials.gov) - P2; N=138; Recruiting; Sponsor: Novartis Pharmaceuticals; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open • Immunology • Osteoarthritis • Pain • Rheumatology • CRP • MRI

Novartis receives FDA fast track designation for LNA043 in osteoarthritis of the knee (Novartis Press Release) - "Novartis today announced that the US Food and Drug Administration (FDA) has granted fast track designation for LNA043 for the treatment for osteoarthritis of the knee....LNA043 is being developed as a potential first in class disease modifying treatment for osteoarthritis (OA)...A Phase IIb study in patients with knee OA is underway."

Fast track designation • CNS Disorders • Osteoarthritis • Pain

A safety and efficacy study of anti-inflammatory (canakinumab) and cartilage stimulating (LNA043) drugs injected into the knee joint of participants with knee osteoarthritis (OA) (clinicaltrialsregister.eu) - P2; N=138; Ongoing; Sponsor: Novartis Pharma AG

Clinical • New P2 trial • Immunology • Musculoskeletal Diseases • Osteoarthritis • Pain • Rheumatology • CRP • MRI

Study of efficacy, safety, and tolerability of LNA043 in patients with knee osteoarthritis (clinicaltrialsregister.eu) - P2; N=550; Ongoing; Sponsor: Novartis Pharma AG

Clinical • New P2 trial • Immunology • Musculoskeletal Diseases • Osteoarthritis • Pain • Rheumatology