Are Nerve Growth Factor Inhibitors the Future of Hip, Knee, or Back Pain Relief?

Aimed at managing osteoarthritis and low back pain, this emerging biologic class of medications may offer new options for those in chronic pain.

If you’re one of the more than 20% of adults dealing with chronic pain, a new kind of medication could be a game-changer. Here’s what you need to know about a new class of biologic drugs, called nerve growth factor (NGF) inhibitors.

What IS NGF in the First Place?

Nerve growth factor is a protein that plays a role in the growth and maintenance of sensory neurons—those are the nerve cells that send messages about physical sensations, like pain and temperature, to your brain.

NGF can also activate pain sensations. When NGF binds to pain receptors inside nerve cells, those receptors become sensitized and initiate a process that can result in acute and chronic pain. High levels of NGF can be found in individuals with conditions like arthritis, chronic headaches, and various generalized pain syndromes.

As PPM recently reported on its clinical site, researchers are testing the ability of NGF inhibitors (technically called anti-NGF monoclonal antibodies) to prevent NGF from binding to pain receptors, thus reducing or stopping the pain-promoting process.

Additional research on NGF inhibitors could provide insight into who else may benefit from the treatment. (Source: 123RF)

NGF Inhibitors in Development

Two NGF inhibitors, tanezumab and fasinumab, are currently in or concluding clinical trials. The Food and Drug Administration (FDA) has fast-tracked tanezumab, being developed by Pfizer and Eli Lilly and Company, for the treatment of osteoarthritis (hip and knee) and moderate-to-severe back pain (tanezumab is also being studied for cancer-related pain). Regeneron Pharmaceuticals’ and Teva Pharmaceuticals’ fasinumab is being studied for patients with chronic pain due to hip or knee osteoarthritis.

Both medications, if approved, will be given via an intravenous (IV) or subcutaneous (SC) under-the-skin injection. Tanezumab has a dosage of 2.5 or 5 mg every eight weeks, while fasinumab has a dosage of 1 or 3 mg every four or eight weeks.

As of late 2019, Eli Lilly and Pfizer planned to file for regulatory submission of tanezumab in the US by early 2020, according to Lars Viktrup, MD, PhD, a senior medical fellow at Eli Lilly & Company. If approved, it may be available on the market by Fall 2020. Fasinumab may be close behind.

Who Might Benefit

In studies to date, NGF inhibitors relieved osteoarthritis pain, and were more effective than both the non-steroidal anti-inflammatory drug (NSAID) naproxen and the opioid pain reliever oxycodone. While there is less research on NGF inhibitors’ effects on chronic lower back pain, at 10 or 20 mg every eight weeks, tanezumab relieved pain better than an NSAID in a recent trial.

“We continue to see a high unmet need in osteoarthritis (OA),” Dr. Viktrup points out. “There are an estimated 27 million Americans living with OA, 11 million of whom suffer from moderate-to-severe OA…Many are unable to achieve adequate pain relief with currently available medications, and there have been no novel classes of treatment approved for OA pain in nearly a decade,” at least not in terms of pharmacology.

In addition, NGF inhibitors could be an option for the significant number of osteoarthritis and lower back pain patients who cannot take NSAIDs, the most commonly used osteoarthritis pain relievers. "There are many contraindications to chronic NSAID use,” observes Dr. Jeffrey Fudin, PharmD. Dr. Fudin is the chief medical officer of Remitigate, LLC, an adjunct associate professor of Pharmacy Practice & Pain Management at New York’s Albany College of Pharmacy & Health Sciences, and Co-Editor-At-Large at PPM.

For instance, he notes that NSAIDs should not be used by people with:

  • coronary artery disease (a kind of heart disease)
  • uncontrolled hypertension (high blood pressure)
  • uncontrolled diabetes, especially in patients who require certain medications to control blood pressure and/or protect against diabetic nephropathy, a type of kidney dysfunction
  • reduced kidney function
  • bleeding disorders.

Those who take anticoagulants (medicines that help prevent blood clots), and those at risk of peptic ulcers should also avoid NSAIDs, Dr. Fudin adds.

Warnings

There are some safety concerns about NGF inhibitors. Some trial participants were shown to be at higher risk of osteonecrosis (the too-quick breakdown of bone); rapidly progressive osteoarthritis, which can result in complete joint destruction; and/or a need for total joint replacement. However, subjects who were on higher doses of NGFs, were also taking NSAIDs, or those who had previously fractured bones were most likely to experience these adverse effects.

Overall, explains Dr. Fudin, “NGFs provide an exciting and unique opportunity in the treatment of various pain syndromes that avoid various characteristic risks and contraindications associated with opioids and NSIADS." That said, he added that "careful monitoring" may be needed in patients who are prescribed NGFs to watch out for potential risks, including osteonecrosis.

Updated on: 02/10/20
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