Photo Credit: Fizkes
The novel, first-in-class neurotrophin-3 (NT-3) inhibitor LEVI-04 demonstrated significant and clinically meaningful analgesia across all measures for patients with osteoarthritis (OA). A significant improvement was reported for all doses in functional measures and patient global assessment (PGA). The study drug was well tolerated.
LEVI-04 is a proprietary p75 neurotrophin receptor fusion protein (p75NTR-Fc) that modulates neurotrophin levels and inhibits NT3, thus alleviating pain. Prof. Philip Conaghan, PhD, from the University of Leeds, in the UK, presented the main results of a randomized phase 2 study (NCT05618782) which assessed the efficacy and safety of LEVI-04 in knee OA1.
The study enrolled 518 patients with radiographic knee OA with a target knee score of greater than or equal to 20 out of 50 on the Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain subscale. The participants’ mean age was about 64 years, mean BMI was 30, and about 56% were women; their mean average daily pain Numeric Rating Scale (NRS) was between 4.0 and 9.0. Participants were randomly assigned to five infusions, given 4 weeks apart, of placebo or 0.3, 0.1, or 2.0 mg/kg LEVI-04 through week 16. The primary endpoint was a change in WOMAC pain in week 17.
LEVI-04 in all three doses was significantly superior to placebo for the primary endpoint at week 17, but also already at week 5. After 17 weeks, the change in WOMAC pain in the placebo group was -2.28, compared with -2.79 (P=0.031), -2.89 (P=0.010), and -3.08 (P<0.001) in the 0.3, 1.0, and 2.0 mg/kg group, respectively. All doses also yielded a significant benefit in exploring secondary outcomes: WOMAC physical function, WOMAC stiffness, and PGA. At week 17, over 50% of the LEVI-04-treated patients reported a greater than or equal to 50% reduction in pain; over 25% reported a greater than or equal to 75% reduction. LEVI-04 was well tolerated; the incidence of treatment-emergent and serious AEs was comparable in all study arms. An oral formulation of LEVI-04 will be developed.
Medical writing support was provided by Michiel Tent
Copyright ©2024 Medicom Medical Publishers
