Levicept says non-opioid drug cuts arthritis pain in phase 2

A non-opioid drug for pain developed by UK biotech Levicept, with a new mechanism of action, has shown it can reduce pain associated with osteoarthritis in a phase 2 trial.

Neurotrophin-3 (NT-3) inhibitor LEVI-04 hit all its primary and secondary objectives in the trial, which enrolled 510 patients with moderate-to-severe osteoarthritis of the knee, raising the hope it could become a non-addictive option for patients needing chronic pain relief.

LEVI-04 was originally discovered at Pfizer's R&D facility in Sandwich, Kent, by Levicept founder Simon Westbrook, and was spun out to be developed by the new company in 2016 in the wake of the big pharma's decision to shut down R&D at the site.

In the phase 2 trial, the drug was administered by intravenous infusion once a month at three doses and compared to a placebo infusion, with the primary endpoint being the change from baseline on WOMAC pain scores at week 17.

According to Levicept, LEVI-04 achieved a reduction of more than 50% for all three doses of the drug tested compared to placebo – all statistically significant improvements – with benefits also seen on secondary measures, including WOMAC subscales of function and joint stiffness, patient global assessment, and daily pain scores. Full data from the study will be presented at a future medical conference.

Levicept chief executive Eliot Forster told pharmaphorum that the company plans to move to subcutaneous administration of LEVI-04 in later-stage development, noting that the current formulation is suitable for both routes.

Regarding the timing and conduct of a phase 3 programme, he said: "We are currently assessing all options for next steps, including a partnership or 'go-it-alone', [and] discussions are ongoing." 

The pharma industry has tried hard to develop non-opioid medications for pain relief for decades, seeking alternatives free of the risk of dependency that has driven an epidemic in overdose deaths in the US and other countries around the world.

A few years ago, efforts crystallised around nerve growth factor (NGF) inhibitors, a class of biologic agents led by Pfizer's tanezumab and Regeneron's fasinumab that showed promise in clinical trials but failed to reach the market, mainly due to safety concerns, including rapidly progressing osteoarthritis (RPOA).

There was no increase in RPOA with LEVI-04 in the phase 2 trial and otherwise the drug was well-tolerated, according to Levicept, a finding that revitalises hopes for a new biologic approach to chronic pain.

There has been more progress in acute pain, with Vertex Pharma filing for approval in the US last month for NaV1.8 sodium channel-targeting candidate suzetrigine as a non-opioid option for pain relief after surgical procedures (abdominoplasty and bunionectomy).

Lead LEVI-04 study investigator Prof Philip Conaghan, director of the NIHR Leeds Biomedical Research Centre in the UK, said the results were "truly exceptional" and suggest that the drug could "offer a vital new treatment option to millions of patients in huge need."

He added: "If phase 3 trials replicate these results, LEVI-04 would represent a major breakthrough for osteoarthritis treatment, and with substantial potential in other pain indications."

Westbrook, who serves as Levicept's chief scientific officer, added that the drug also "retains the important trophic effects of the neurotrophins, including joint re-modelling," which could confer benefits beyond pain relief in osteoarthritis.

Forster told us that Levicept intends to focus on osteoarthritis for the time being, with a label expansion into other pain settings coming after an initial approval in that indication.