Wanted: Drug developers to take on the unmet need of translating non-opioid treatments for chronic pain.

It could be a huge opportunity, but sponsors must look beyond what works for acute pain and take a precision medicine approach to find the right treatment for individual patients. In doing so, they could help in the fight against the growing epidemic of opioid addiction.

That's the message several speakers delivered to the FDA Science Board Tuesday.

For the past 15 years, treatment for chronic pain has been opioid-centric, Daniel Alford, director of the Safe and Competent Opioid Prescribing Education program at the Boston University School of Medicine, told the board.

While those single therapies work for acute pain, they don't necessarily help with chronic pain. Only about 50 percent of patients with chronic pain get relief from an opioid, he said. That leads to higher doses, and the potential for addiction, for those who don't respond.

Chronic pain has been described as pain that persists more than three months or beyond the time expected for healing. But treating chronic pain as persistent acute pain is the road to failure, Alford said. Instead, it should be considered a disease, not a symptom. The science around pain is complicated and confusing. "We really don't understand the mechanism" of chronic pain, he added.

Unlike acute pain, which may stem from surgery or an injury to a specific part of the body, chronic pain is related to a structural remodeling of the central nervous system (CNS), Alford said.

Because of the CNS involvement, patients with chronic pain often have overlapping problems, including fibromyalgia, irritable bowel syndrome, headaches and temporomandibular joint dysfunction, said Daniel Clauw, a professor of pain management and anesthesiology at the University of Michigan School of Medicine.

Chronic pain, which has genetic and environmental risk factors, should be seen as a continuum that's not likely to respond to opioids, he said. Opioids actually could make the condition worse in some patients. There's also no evidence that nonsteroidal anti-inflammatory drugs (NSAIDS), an alternative to opioids used in acute pain, are effective in treating chronic pain.

Serotonin-norepinephrine reuptake inhibitors and other CNS drugs have been shown to work, off-label, in treating chronic pain, but Clauw said these older drugs are off patent, so industry has shown little interest in developing them for the indication.

"The problem here is our hands are somewhat empty," the FDA's Janet Woodcock said of the current armamentarium for treating pain, be it acute or chronic. The only approved alternatives to opioids are several NSAIDS and acetaminophen. Woodcock is hopeful that a pipeline of alternatives will be flowing soon.

In the meantime, several speakers recommended more education on pain management to curb the misuse of opioids. Alford noted that Canadian veterinary schools provide five times as much instruction on pain management than the medical schools in the country.

Educating doctors would make a big difference in how pain is treated and opioids dispensed.

The risk evaluation and mitigation strategies (REMS) required for long-acting and extended-release opioid formulations aren't helping, Clauw said, because they're shooting for the wrong target. The REMS are intended for patients with chronic pain who are purposely being started on an opioid. But experts in pain management wouldn't purposely use an opioid to treat chronic pain, Clauw said. The REMS should target the acute pain environment instead, as most patients staying on an opioid likely were introduced to it post-surgery.

GO-TO STANDARD

The resulting addiction stems from prescribing practices, something that's outside the FDA's purview. Patients need an opioid for only a day or two to manage pain after surgery, said Mary Jeanne Kreek, a professor on addictive diseases at Rockefeller University. Yet many doctors initially prescribe a 14- to 30-day supply of the drugs.

Part of the problem is that many doctors view opioids as the go-to gold standard for treating both acute and chronic pain, as evidenced by a few of the comments made during the public hearing session of Tuesday's meeting.

Payers also add to the problem. Since generic opioids are available, payers often insist on opioids being used as first-line pain treatments as opposed to newer, less addictive drugs that could be more expensive, Peter Pitts, president of the Center for Medicine in the Public Interest, told the Science Board during the hearing.

Some of the board's discussion focused on abuse-deterrent properties for opioids. Don Flattery, whose 26-year-old son died 18 months ago from an opioid overdose, took the FDA to task for its focus on abuse. That attitude implies opioids are safe when used properly and deflects attention from the need to develop nonaddictive alternatives, he said.

There is no safe way to take opioids for chronic pain, said Joseph Adams, who for years used opioids to treat patients with noncancer chronic pain.

At the time, he said, he was reassured that he was complying with the FDA-approved label and that he could prevent addiction by following the safeguards. Today, he realizes how much harm he did to his patients by prescribing the drugs.

The biggest danger for patients is taking the drugs as prescribed, Adams said.

They follow the rules until they become addicted. "Using opioids for chronic pain is like taking off in a plane with no landing gear," he added.