FDA: Continue Study of Antinerve Growth Factors for Pain

SILVER SPRING, MD. – The clinical development of antinerve growth factors as a treatment for pain should continue, despite reports of serious joint-related adverse effects associated with these agents in clinical trials, a Food and Drug Administration panel unanimously agreed on March 12.

At the meeting, the FDA’s Arthritis Advisory Committee voted 21-0 that there was a role for the ongoing development of antinerve growth factors (anti-NGF), which panelists agreed appeared to show promise as analgesics in studies and may eventually have a niche in the treatment of chronic pain conditions. But they strongly recommended that future studies should closely monitor patients for rapidly progressing osteoarthritis (OA) and other joint-related adverse events that have been observed in trials, and include a rigorous informed-consent process so that patients are well informed about the potential risks. The panel also recommended that the manufacturers of these products conduct studies to investigate the mechanism behind the joint-related adverse events, and that in clinical trials, the use of concomitant NSAIDs should be contraindicated or limited.

The FDA convened the panel to discuss reports of joint destruction in patients treated with two of the three agents in clinical development, which resulted in a hold on clinical trials of all three agents, tanezumab (Pfizer), fulranumab (Janssen), and REGN475 (Regeneron). Anti-NGF agents, monoclonal antibodies directed against nerve growth factor, are being studied for chronic pain caused by various conditions, primarily osteoarthritis. The greatest amounts of data are available on tanezumab, which was being studied in phase III trials of patients with OA and chronic low back pain.

The FDA put a hold on clinical trials of the three anti-NGF factors in 2010, after cases of osteonecrosis and avascular necrosis were reported in osteoarthritis patients treated with tanezumab and in those treated with fulranumab, because of concerns that these cases might be a class effect. There were no such cases among patients on placebo or comparator drugs. The risk increased further among those on an NSAID and an anti-NGF agent, compared with the anti-NGF agent alone.

Panelists agreed with the FDA reviewers that that these cases were unusual and severe.

In addition to OA, the companies are developing these agents for other chronic pain conditions, including low back pain, postherpetic neuralgia, chronic pancreatitis, endometriosis, and cancer pain.

The FDA usually follows the recommendations of its advisory panels. Panelists have been cleared of potential conflicts of interest related to the topic of the meeting. Occasionally, a panelist may be given a waiver, but not at this meeting.

SILVER SPRING, MD. – The clinical development of antinerve growth factors as a treatment for pain should continue, despite reports of serious joint-related adverse effects associated with these agents in clinical trials, a Food and Drug Administration panel unanimously agreed on March 12.

At the meeting, the FDA’s Arthritis Advisory Committee voted 21-0 that there was a role for the ongoing development of antinerve growth factors (anti-NGF), which panelists agreed appeared to show promise as analgesics in studies and may eventually have a niche in the treatment of chronic pain conditions. But they strongly recommended that future studies should closely monitor patients for rapidly progressing osteoarthritis (OA) and other joint-related adverse events that have been observed in trials, and include a rigorous informed-consent process so that patients are well informed about the potential risks. The panel also recommended that the manufacturers of these products conduct studies to investigate the mechanism behind the joint-related adverse events, and that in clinical trials, the use of concomitant NSAIDs should be contraindicated or limited.

The FDA convened the panel to discuss reports of joint destruction in patients treated with two of the three agents in clinical development, which resulted in a hold on clinical trials of all three agents, tanezumab (Pfizer), fulranumab (Janssen), and REGN475 (Regeneron). Anti-NGF agents, monoclonal antibodies directed against nerve growth factor, are being studied for chronic pain caused by various conditions, primarily osteoarthritis. The greatest amounts of data are available on tanezumab, which was being studied in phase III trials of patients with OA and chronic low back pain.

The FDA put a hold on clinical trials of the three anti-NGF factors in 2010, after cases of osteonecrosis and avascular necrosis were reported in osteoarthritis patients treated with tanezumab and in those treated with fulranumab, because of concerns that these cases might be a class effect. There were no such cases among patients on placebo or comparator drugs. The risk increased further among those on an NSAID and an anti-NGF agent, compared with the anti-NGF agent alone.

Panelists agreed with the FDA reviewers that that these cases were unusual and severe.

In addition to OA, the companies are developing these agents for other chronic pain conditions, including low back pain, postherpetic neuralgia, chronic pancreatitis, endometriosis, and cancer pain.

The FDA usually follows the recommendations of its advisory panels. Panelists have been cleared of potential conflicts of interest related to the topic of the meeting. Occasionally, a panelist may be given a waiver, but not at this meeting.

SILVER SPRING, MD. – The clinical development of antinerve growth factors as a treatment for pain should continue, despite reports of serious joint-related adverse effects associated with these agents in clinical trials, a Food and Drug Administration panel unanimously agreed on March 12.

At the meeting, the FDA’s Arthritis Advisory Committee voted 21-0 that there was a role for the ongoing development of antinerve growth factors (anti-NGF), which panelists agreed appeared to show promise as analgesics in studies and may eventually have a niche in the treatment of chronic pain conditions. But they strongly recommended that future studies should closely monitor patients for rapidly progressing osteoarthritis (OA) and other joint-related adverse events that have been observed in trials, and include a rigorous informed-consent process so that patients are well informed about the potential risks. The panel also recommended that the manufacturers of these products conduct studies to investigate the mechanism behind the joint-related adverse events, and that in clinical trials, the use of concomitant NSAIDs should be contraindicated or limited.

The FDA convened the panel to discuss reports of joint destruction in patients treated with two of the three agents in clinical development, which resulted in a hold on clinical trials of all three agents, tanezumab (Pfizer), fulranumab (Janssen), and REGN475 (Regeneron). Anti-NGF agents, monoclonal antibodies directed against nerve growth factor, are being studied for chronic pain caused by various conditions, primarily osteoarthritis. The greatest amounts of data are available on tanezumab, which was being studied in phase III trials of patients with OA and chronic low back pain.

The FDA put a hold on clinical trials of the three anti-NGF factors in 2010, after cases of osteonecrosis and avascular necrosis were reported in osteoarthritis patients treated with tanezumab and in those treated with fulranumab, because of concerns that these cases might be a class effect. There were no such cases among patients on placebo or comparator drugs. The risk increased further among those on an NSAID and an anti-NGF agent, compared with the anti-NGF agent alone.

Panelists agreed with the FDA reviewers that that these cases were unusual and severe.

In addition to OA, the companies are developing these agents for other chronic pain conditions, including low back pain, postherpetic neuralgia, chronic pancreatitis, endometriosis, and cancer pain.

The FDA usually follows the recommendations of its advisory panels. Panelists have been cleared of potential conflicts of interest related to the topic of the meeting. Occasionally, a panelist may be given a waiver, but not at this meeting.