The European Alliance of Associations for Rheumatology (EULAR) Annual Meeting, one of the important yearly events in Rheumatology, took place this past weekend. Out of the entire data that was presented for osteoarthritis, some potential ones targeting a specific patient population, having a novel mechanism of action, or providing a new treatment option are cherry-picked and summarized below. 

1. Abstract #LBA0011

Phase I Clinical Trial of PPV-06: Safety, Immunogenicity, and Effects on Biomarkers in Knee Osteoarthritis Patients 

PPV-06 vaccine is the most advanced product from Peptinov’s pipeline. The company presented early safety data from Phase I study (NCT04447898; Completed) for the treatment of knee osteoarthritis. PPV-06 is an IL-6-derived peptide coupled with a carrier protein, CRM197. The goal of the PPV-06 active immunotherapy is to induce the production of anti-IL-6 antibodies to buffer its biological activity. 

According to the data presented in 24 randomized patients, no dose-limiting toxicities (DLTs) were observed. Adverse events (AEs) induced by PPV-06 were mostly mild to moderate and transient, including injection site reactions, myalgia, back pain, headache, and pruritus. All AEs were treatment-emergent, except for one ongoing event at baseline. In the PPV-06 low dose group, one patient discontinued due to a Grade 2 injection site reaction. No serious AEs or study discontinuations due to serious treatment-emergent adverse events (TEAEs) were reported.

Anti-IL-6 antibodies were detected in both PPV-06 groups but not in the placebo group. Transient increases in IL-6 levels without a corresponding increase in hsCRP were noted, indicating immune complex formation and reduced inflammation. No T-cell responses against IL-6 were observed, suggesting no autoreactive T cells post-vaccination. Serum biomarkers for osteoarthritis showed a downward trend in C2M and C3M levels in the PPV-06 groups compared to placebo. There was a non-statistically significant trend toward improved Knee Injury and OA Outcome Score (KOOS), especially for quality of life and symptoms, while Numerical Rating Scale (NRS) pain scores remained unchanged. This result marks a notable achievement in advancing the development of PPV-06 active immunotherapy for managing patients with inflammatory knee osteoarthritis.

KOL Insight

“IL-6 Immunotherapy for knee OA PPV-06 FTIH Phase I. Is it safe? Yes, with no serious AEs in 6-month follow-up. Is it immunogenic? Apparently so, IL-6 Ab & neutralizing Ab. Does it work? Will have to wait for Phase II” – MD, PhD, UK

2. Abstract #OP0326

Long-Term Radiographic and Pain Outcomes of Repeat Lorecivivint Injections in Severe Knee Osteoarthritis: Results from a Phase III Extension Study (OA-07) 

Biosplice’s Lorecivivint, an intra-articular CLK/DYRK inhibitor known to influence Wnt and inflammatory pathways, has demonstrated safety, improved patient-reported outcomes, and preserved radiographic medial joint space width (JSW) compared to placebo in previous studies.

According to the latest results from Phase III Extension Study  (OA-07; NCT04520607) presented at the conference in the study, 276 patients were enrolled. Lorecivivint appeared safe and well-tolerated, with no major differences in adverse events compared to the placebo.

Comparing lorecivivint to placebo in the full analysis set (FAS) completers:

• At 24 months, lorecivivint showed a slight reduction in medial joint space width (JSW) loss compared to placebo (-0.11 vs. -0.20), with improvements in the Western Ontario and McMaster Universities Arthritis Index (WOMAC) Pain (-5.18) and WOMAC Function scores (-4.90).

• At 36 months, lorecivivint demonstrated less medial JSW loss than pre-crossover placebo measures.

Comparing lorecivivint to placebo in Kellgren and Lawrence Grade 2 (KL2) FAS completers:

• At 24 months, lorecivivint showed a minimal difference in medial JSW loss compared to placebo (0.00 mm vs. -0.08 mm). 

• At 36 months, lorecivivint showed improved medial JSW compared to pre-crossover placebo measures.

KOL Insight

“A new treatment method combining Wnt pathway modulators with intra-articular CLK2/DYRK1A inhibitors could be a promising therapy for treating osteoarthritis. Lorecivivint was found to significantly improve WOMAC discomfort, WOMAC function, and joint space width in osteoarthritis patients.” – PhD, China

Conclusion

As per DelveInsight’s estimates, Osteoarthritis is a highly prevalent condition affecting about 40 million people (in 2024) in the United States. The market for osteoarthritis is valued at about USD 40 billion in the 7MM by 2032, with the US holding the largest share of the market. 

Currently, the classes used for the treatment of osteoarthritis include NSAIDs, Opioids, intra-articular Corticosteroids, intra-articular Hyaluronic acid, and others. A market trend in recent years has been toward favoring treatments with efficient techniques and few injections. An intra-articular 5-injection viscosupplements for the treatment of knee osteoarthritis are progressively dropping as users tend to favor products that require the fewest injections, and outpatient services are declining. The use of single injections is anticipated to rise in the coming years due to the following reasons: single-injection hyaluronic acid therapies lessen patient exposure to injection procedures, maximize the likelihood of treatment completion/compliance, and improve patient and healthcare professional convenience. 

Disease-modifying osteoarthritis drugs could offer new therapeutic targets to restore the quality and function of tissues affected by osteoarthritis. The advantage of PPV-06 vaccination is that it stimulates the immune system to produce antibodies that are specific to IL-6. The biological activity of IL-6, which is involved in the body's inflammatory process, will be neutralized by the antibodies generated. Although PPV-06 is still in the early stages of development and its future is difficult to predict, DelveInsight's analysis indicates that lorecivivint will likely generate approximately USD 520 million in the 7MM (the US, EU4 (Germany, France, Italy, and Spain), the UK, and Japan) by 2032. The safety of lorecivivint was confirmed, and the OA-07 study successfully achieved its primary goal by demonstrating improved medial JSW with repeat lorecivivint injections compared to placebo over 3 years. These findings indicate that lorecivivint remains a promising and safe treatment option for knee osteoarthritis with potential disease-modifying effects.