The US opioid crisis has escalated over the past decade, with the country consuming 80% of the world’s opioid supply.

This habit that kills 91 Americans each day and there is an urgent need for a safe alternative pain management therapeutic that does not pose a risk for drug abuse.

Novel therapies lacking abuse potential

The nerve growth factor (NGF) inhibitors are key contenders in late-stage drug development that reduce pain by a novel mechanism of action.

In contrast to opioids, which alter pain perception and induce euphoria by targeting opioid receptors, NGF inhibitors block signalling of NGF, which increases in response to injury, inflammation, or chronic pain.

This is thought to prevent pain signals from reaching the brain and spinal cord.

Tanezumab gains fast-track designation

NGF inhibitors are being investigated across several pain indications including osteoarthritis pain and cancer pain. Much of the clinical data is promising.

In clinical trials for osteoarthritis pain, NGF inhibitors have consistently demonstrated superiority to placebo across a variety of dosages.

In addition, Pfizer and Eli Lilly’s tanezumab was proven to reduce osteoarthritis pain in a Phase III trial to a greater extent than oxycodone, a commonly used opioid.

The drug was granted fast-track designation by the US Food and Drug Administration (FDA) in June 2017, and if approved could reach the market by late 2018 or early 2019.

NGF inhibitor development: a risky business

Some serious safety concerns surround this drug class. Most notably, the FDA placed a hold on all NGF-inhibitor clinical trials in 2010 following reports of patients suffering rapid joint destruction, culminating in joint replacement.

An independent committee subsequently determined that more study was necessary to fully understand the risk to bones and joints, but still voted in favour of continued drug development due to the strong potential benefit of anti-NGF therapy, and the absence of any direct link to joint destruction. This led to the hold being lifted.

The drug class also includes a number of high-profile failures, including fulranumab, which was discontinued in Phase III development in 2016.  

NGF inhibitor development is evidently high-risk, and pivotal safety data will require heavy scrutiny.

 However, if approved, these products could achieve blockbuster status, thanks to their potential to help prevent opioid abuse.