LEVI-04 Significantly Improves Pain and Function in Knee Osteoarthritis, finds study

Osteoarthritis is one of the leading causes of chronic pain and disability, and highly effective alleviating therapies lack. "The therapy target has been excess neurotrophins, associated with OA and other pain conditions". Earlier NGF-targeting therapies were effective in pain but resulted in serious joint complications. LEVI-04 is a first-in-class fusion protein, supplementing endogenous p75NTR to modulate the activity of neurotrophin and inhibit NT3, which has given promising preclinical and Phase I safety results. In this study, LEVI-04's efficacy and safety were evaluated in patients suffering from knee OA.

It was a 20-week, multicenter RCT conducted in Europe and Hong Kong, which included 518 participants who were affected with painful (≥4/10 WOMAC) and radiographic (KL≥2) knee OA. The participants were randomized to receive either intravenous placebo or LEVI-04 at doses of 0.3, 0.1, or 2 mg/kg every four weeks until week 16 followed by safety follow-up until week 30.

• Primary endpoint: Change in WOMAC pain score at week 17.

• Secondary endpoints: Function, Patient Global Assessment, and more than 50% responder analyses on pain.

• Imaging: Baseline inclusion/exclusion and safety assessment was done by X-rays of 6 major joints and MRI of knees.

Patient Profile:

• Mean age: 63.1–65.4 years.

• Mean BMI: 29.3–30.3.

• Female patients: 51.5–61.5%

Efficacy:

• WOMAC pain and function, both significantly improved from week 5 and week 17 (p < 0.05 compared with placebo for all dose levels).

• A majority (>50%) of patients treated with LEVI-04 had ≥50% pain, and >25% had ≥75% pain at weeks 5 and 17.

Safety:

• LEVI-04 was well-tolerated with no increase in serious adverse events (SAEs), treatment-emergent adverse events (TEAEs), or joint pathologies compared to placebo.

• Incidence of anti-drug antibodies was low: 9 participants tested positive pre-dosing, and 6 tested positive during the study at the lowest detection limits.

LEVI-04, displayed significant and clinically relevant pain and function improvements while maintaining robust safety at all doses. This novel therapy seems to support the supplementation strategy of endogenous p75NTR for the treatment of OA and other pain diseases. Based on these promising Phase II results, Phase III studies are currently being designed to further evaluate the potential of LEVI-04 to revolutionize OA treatment.

Reference:

LEVI-04, a novel neurotrophin-3 inhibitor, substantially improves pain and function without deleterious effects on joint structure in people with knee osteoarthritis: A randomized controlled phase II trial. (2024, October 15). ACR Meeting Abstracts. https://acrabstracts.org/abstract/levi-04-a-novel-neurotrophin-3-inhibitor-substantially-improves-pain-and-function-without-deleterious-effects-on-joint-structure-in-people-with-knee-osteoarthritis-a-randomized-controlled-phase-ii/