The present study did not provide any confirmation regarding the analgesic efficacy of Fulranumab in neuropathic populations.

The occurrence of neuropathic pain is quite significant these days affecting around 8% of general population. Neuropathic pain could be a result of postherpetic neuralgia (PHN) or post-traumatic neuropathy (PTN) that develops due to nerve injury by trauma or surgery. Neuropathic pain is often hard to treat and may result in persistent pain and disability. Postherpetic neuralgia, a result of herpes zoster, is described by long-lasting pain after the onset of rash or subsequent cutaneous healing. First line treatment for pain related to PHN comprises tricyclic antidepressants, serotonin-noradrenaline reuptake inhibitors, pregabalin, and gabapentin. Second-line treatment includes lidocaine patches, capsaicin high-concentration patches, and tramadol whereas third-line therapy encompasses strong opioids and botulinum toxin. Most of the drugs offer unwanted side effects and often take several weeks to reach target plasma levels, leading to reduced patient compliance. Post traumatic neuropathy is treated via nonsteroidal anti-inflammatory drugs, opioids, and gabapentin. Both PHN and PTN can significantly harm the quality of life and may also lead to increased health care utilization costs. Studies have shown that neuronal hyperactivity can be normalized by inhibiting the effect of nerve growth factor (NGF). Fulranumab is a human recombinant immunoglobulin-G2 inhibitor that particularly counteracts biological actions of human NGF.  Clinical studies have confirmed the efficacy of Fulranumab in treating pain related to knee and hip osteoarthritis and painful diabetic peripheral neuropathy.

Rationale behind the research:

More effective therapies for the management of neuropathic pain remain a critical unmet medical need. The present study was conducted to explore the efficacy of relatively newer drug “Fulranumab” for treating pain associated with PHN and PTN.

Objective:

To explore the analgesic efficacy, safety, and tolerability of subcutaneous (SC) Fulranumab for the treatment of PHN and PTN.

Study outcomes:

• Primary endpoints: included average pain intensity over the last 24 hours, using an 11-point NRS, where 0 = no pain and 10 = pain as severe as you can imagine, collected through Interactive Voice Response System (IVRS)
• Secondary endpoints: included daily assessment of "worst pain in the past 24 hours" collected through IVRS, Neuropathic pain symptom inventory (NPSI), Brief Pain Inventory-short form (BPI-SF), Patient Global Assessments of Change (PGIC), and pain responder analysis

Time Points:  Baseline and week 12

Study Outcomes

Primary endpoints: It was assumed that Fulranumab would establish a positive dose-response relationship in PHN by reducing average pain intensity. No significant dose-response was observed in the PHN patients. No substantial changes in paired-wise analysis in average pain intensity were witnessed from baseline to the end of the study (week 12) for both the PHN and PTN groups compared with placebo at either week 4 or week 8 of the 12-week DB efficacy phase, except for the 10 mg group (P = 0.02; week 4) in PHN patients.

Figure 1: Change from Baseline to Week 12 in the Average Pain Intensity Score in PHN population

Figure 2: Change from Baseline to week 12 in Average Pain Intensity Score in PTN population

Secondary endpoints: Across all Fulranumab treatment groups, no significant differences in worst pain in the past 24 hours were observed as compared to placebo in PHN and PTN groups, at the week 12 endpoint. When measured by the BPI-SF scale, a significant improvement from baseline in treatment pain relief subscale was observed only for the Fulranumab 3 mgQ4 wk group (P=0.04) in the PHN population, but there was no improvement in the PTN patients. For the NPSI total scores, no improvements were observed from baseline to the end of DB efficacy phase in the Fulranumab treatment groups as compared with placebo in either population. At the 12-week endpoint, there were no significant differences noted for any of the Fulranumab treatment groups compared with placebo. Almost half of the PHN (55% for both placebo and Fulranumab groups) and PTN (43% for placebo and 48% for the Fulranumab 10 mgQ4 wk group) patients reported their status as "not changed" as measured by PGIC.

The present study failed to demonstrate that Fulranumab at a dose up to 10 mg once every 4 weeks, compared with placebo, was effective in alleviating pain in patients with PHN or PTN. However, the highest dose of Fulranumab (10 mg Q 4 wk) showed some reduction in pain at the 4-week time point.

In previous studies, Fulranumab has shown considerable pain reduction in patients with chronic osteoarthritis of the knee or hip and diabetic neuropathy. But, it failed to show analgesic activity in either of the neuropathic patients involved in this study. More comprehensive clinical studies involving more patients are needed to fully characterize the efficacy of fulranumab, ideally with an active comparator. Also, clinical studies evaluating long-term safety and tolerability of this potentially new class of analgesic drug are required. The results of the present study suggest that Fulranumab is not effective in relieving pain of PHN or PTN patients.