UK's Levicept builds case for osteoarthritis therapy at ACR
Graphical representation of LEVI-04 mechanism.
New data from a phase 2 trial Levicept's LEVI-04 in patients with osteoarthritis (OA) have backed its potential to both address pain and reduce the progression of the disease.
The Sandwich, UK-based biotech reported new results from the study at the American College of Rheumatology (ACR) annual congress in Orlando this week, saying LEVI-04 has the potential to become "the first new systemic treatment for OA in over two decades."
Previously reported data from the 518-patient study, published in The Lancet earlier this year, showed significant improvements in pain using the WOMAC scale compared to placebo, with improvements in joint function, and was well-tolerated.
At ACR, Levicept reported results from an ex vivo study of LEVI-04 that looked at the effects of the drug on neurotrophin-3 (NT-3) in plasma samples taken from patients enrolled in the phase 2 trial, providing evidence of the drug's supposed mechanism of action.
In a healthy joint, neurotrophins support nerve survival and tissue repair and are regulated by a chaperone protein called soluble p75NTR. In OA, the balance is disrupted, allowing levels of NT-3 to rise, which in turn amplifies pain signals and drives joint breakdown.
Previous attempts to suppress neurotrophins in OA have focused on antibody-based inhibitors of nerve growth factor (NGF), which were shown in clinical trials to limit pain but were abandoned as they also caused rapidly progressive joint destruction. The side effects have been attributed to complete blockade of NGF, which is believed to play a role in joint repair processes.
At ACR, Levicept was able to demonstrate that LEVI-04 – a chimeric fusion protein that supplements p75NTR levels – was able to inhibit excess NT-3 whilst also preserving NGF function, allowing it to continue its beneficial role in bone and cartilage remodelling.
Levicept also presented additional data at ACR on Patient Acceptable Symptom State (PASS), a scale designed as a measure of patients 'feeling well'.
LEVI-04, especially at higher doses, was consistently associated with a high proportion of the participant population achieving both PASS and a low strict symptom state for both pain and function, as well as a shorter time to response compared to placebo.
The results show that LEVI-04 "supports a return to neurotrophin homeostasis and preserves physiological NGF signalling for joint health maintenance," said Levicept's founder and chief executive Simon Westbrook.
The UK biotech is preparing for a phase 3 development programme for LEVI-04, after the FDA accepted its Investigational New Drug (IND) application earlier this year.
It recently appointed James Sandy as its chief development officer and Darlene Deptula-Hicks as chief financial officer to oversee late-stage clinical testing and financing of the programme.
