The anti-NGF monoclonal antibody fulranumab performed well in a clinical trial of patients with moderate-to-severe knee or hip osteoarthritis pain.
In the Janssen-funded study, published online March 7 in Arthritis & Rheumatology, researchers compared the safety and efficacy of five different dosages of subcutaneous fulranumab to placebo for patients with hip or knee pain caused by osteoarthritis.
Led by Panna Sanga, M.D, of Janssen Research and Development, the goal of the study was to better understand the utility of fulranumab as adjunctive therapy to standard therapy.
Despite the monthly dosing regimen and long half-life of fulranumab, patients experienced pain relief within a short period of time. “Fulranumab (at 3 mg every four weeks and 10 mg every eight weeks) provided continued effective relief of pain associated with knee and hip osteoarthritis as early as week four, which was maintained up to week 53,” wrote Dr. Sanga and colleagues.
Osteoarthritis in the knee or hip is a major cause of pain for patients, contributing to reduced quality of life and limitations with daily functioning. Current strategies for reducing osteoarthritis pain include pharmacologic agents (e.g., nonsteroidal anti-inflammatory drugs [NSAIDs]), topical ointments, opioids, antidepressants, and non-pharmacologic interventions such as psychological counseling and lifestyle modifications.
Recently, regulatory groups have been calling for demonstration of maintained efficacy of new pharmacologic agents (e.g., analgesics) beyond the 12 weeks typically required. Fulranumab is a human anti–nerve growth factor (anti-NGF) monoclonal antibody. In a prior 12-week efficacy study, fulranumab was shown to have significant efficacy for improving pain and physical functioning in patients with moderate-to-severe chronic osteoarthritis.
To date, there have been limited long-term efficacy studies of existing pharmacologic agents. Moreover, few long-term placebo-controlled studies have shown sustained analgesic efficacy specifically in osteoarthritis.
The overall study included a 3-week screening phase, a 12-week double-blind efficacy phase, a 92-week double-blind extension phase, and a 26-week posttreatment follow-up phase. Here, we focus on the results from the 12-week double-blind efficacy phase.
This was a phase II, randomized, placebo-controlled extension study conducted with 401 patients from 85 sites in Canada, Poland, Korea, and the United States. Patients enrolled in the study between September 2009 and August 2011, and were between the ages of 40-80, had osteoarthritis in the hip or knee, were receiving stable analgesic regimens of NSAIDs and/or long-acting or immediate-release opioids, and had a mean osteoarthritis pain intensity score of ≥5 (using an 11-point scale).
Patients were randomized (1:1:1:1:1:1) to placebo or 1 of 5 of the following treatments: fulranumab regimens administered as subcutaneous injections (1 mg every 4 weeks, 3 mg every 8 weeks, 3 mg every 4 weeks, 6 mg every 8 weeks, and 10 mg every 8 weeks),.
Efficacy outcomes included changes over time from baseline in scores on the pain and physical
function subscales of the Western Ontario and McMaster Universities Osteoarthritis Index and the patient’s global assessment. Safety outcomes included evaluations of treatment-emergent adverse events, clinical laboratory test results, vital signs, findings from physical examinations, 12-lead electrocardiogram, and injection sites.
A major finding was that long-term sustained improvements were observed in all efficacy parameters following fulranumab treatment of 1 mg every 4 weeks, 3 mg every 4 weeks, and 10 mg every 8 weeks, compared with placebo.
The incidence of treatment-emergent adverse events was similar in the placebo group (88%) and the fulranumab groups (91%); all phases. The most common treatment-emergent adverse events reported among all fulranumab-treated patients were arthralgia (21%), osteoarthritis (18%), paresthesia (13%), and upper respiratory tract infection (13%), whereas arthralgia (15%), osteoarthritis (14%), and sinusitis (12%) were most common in the placebo group.
Approximately 15 patients (21%) had rapid progression of osteoarthritis (RPOA). It should be noted that all cases of rapid progression of osteoarthritis occurred in patients treated with fulranumab who were concurrently receiving nonsteroidal anti-inflammatory drugs and occurred in joints with preexisting osteoarthritis.
“In this long-term, placebo-controlled study, fulranumab was generally well-tolerated in patients with chronic OA knee or hip pain, with the exception of RPOA emerging as a safety signal,” wrote Sanga and the research team. “Additional long-term studies comparing fulranumab therapy with current standard-of care treatment are warranted to demonstrate sustained efficacy and to assess the safety/tolerability of lower doses of fulranumab without concomitant use of long-term NSAIDs.”
This study was supported by Janssen Research & Development.
Dr. Katz has received consulting fees from Janssen Research & Development (more than $10,000). Dr. Katz is an employee of Analgesic Solutions.
Panna Sanga, Nathaniel Katz, Elena Polverejan, et al. "Long-Term Safety and Efficacy of Fulranumab in Patients With Moderate-to-Severe Osteoarthritis Pain," Arthritis & Rheumatology. Published online March 8, 2017. DOI: 10.1002/art.39943.