Fasinumab improves pain, function in OA
Fasinumab, a recombinant, fully-human anti-nerve-growth-factor antibody, improved pain and physical function in patients with osteoarthritis, at various dose levels, even among individuals who experienced little benefit from previous analgesic therapy, according to recent findings in Arthritis & Rheumatology.
“Biologic agents that specifically block [nerve growth factor (NGF)] to treat pain may obviate many of the side effects of currently used analgesic medications, such as opioids and nonsteroidal anti-inflammatory drugs (NSAIDs), which rely on different mechanisms of action,” Paula Dakin, MBChB, of Regeneron Pharmaceuticals, and colleagues wrote. “This new therapeutic could benefit patients experiencing pain of osteoarthritis (OA) ... However, NGF-directed therapies exhibit their own unique side effect profile in OA, which includes alterations of peripheral sensation and arthropathies.”
To analyze the efficacy and safety of fasinumab (Regeneron Pharmaceuticals) in patients with OA pain, Dakin and colleagues conducted a phase 2b/3, double-blind, placebo-controlled study of 421 patients at 61 sites across the United States. Eligible participants included adults aged 40 to 80 years with radiologically-confirmed knee and/or hip OA. Participants also demonstrated moderate-to-severe OA pain both while using their usual analgesic therapy and at randomization, which occurred 7 days after analgesic withdrawal.
Participants were randomly selected to receive either 1mg, 3mg, 6mg or 9mg doses of fasinumab, or placebo, every 4 weeks during a period of 16 weeks. Patients were followed to week 36. Efficacy endpoints included change from baseline Western Ontario and McMaster Universities Osteoarthritis Index pain and physical function subscale scores at week 16, as well as Patient Global Assessment. In addition, the researchers examined joints through scheduled assessments during treatment and follow-up. Among the 421 participants, 342 completed the full 36-week follow-up period.
According to the researchers, patients in all fasinumab dose groups demonstrated statistically significant decreases in pain compared with placebo, without any clear dosedependence. Physical function and Patient Global Assessment similarly improved in patients treated with fasinumab, compared with the placebo group.
The adverse event rate across the fasinumab groups was 17%, compared with 10% for patients who received placebo. Discontinuation rates were 4% for fasinumab and 1% for placebo. The researchers noted 25 cases of arthropathies — 7% among patients treated with fasinumab and 1% in the placebo group. These cases were dosedependent fashion, with two occurring at the lowest dose and 10 at the highest dose. Among the 25 cases, 16 were asymptomatic and discovered with scheduled radiographs. There was one treated case of destructive arthropathy, which occurred in the 6mg group.
“In this phase 2b/3 study involving > 400 patients, fasinumab demonstrated a substantial degree of analgesia in patients with moderate-to-severe pain from OA — without clear evidence of efficacy dependence on dose level — even in patients who had not experienced benefits with prior analgesics, a group previously excluded in most other pain studies in osteoarthritis,” Dakin and colleagues wrote. “This represents an important, previously unaddressed patient population.”
“Fasinumab was well tolerated by most patients, with a clear dose-dependent increase in joint-related abnormalities,” they added. “The observation that efficacy at lower doses was similar to that of higher doses, but with lower rates of arthropathy, demands that future studies explore the benefit-risk at these lower doses.” – by Jason Laday
Disclosure: Dakin reports employment with Regeneron Pharmaceuticals. Please see the full study for additional authors’ disclosures.