Non-Opioid Treatment Alternatives For Pain Face Clinical Development And Reimbursement Challenges

Pain impacts tens of millions of Americans on a daily basis. Chronic pain, in particular, has a persistently deleterious effect on people’s ability to function, as well as their mental health and quality of life.

Managing pain often involves a balancing act, in which doctors, patients, and payers must consider appropriate forms of treatment – both pharmaceutical and non-pharmaceutical interventions – in the proper context. With respect to pharmaceutical therapies, physicians must assess the benefits and risks of both non-opioid and opioid treatments.

Some experts have suggested that curbs on prescribing opioids have caused the pendulum to swing too far in the direction of severely limiting prescription opioids – even forced tapering – as such medicines do have legitimate uses for persons suffering from pain. Hence, yesterday the Centers for Disease Control and Prevention (CDC) issued updated guidelines on opioid prescribing, which are less proscriptive and more flexible. For example, public health officials recognize in the new guidelines the importance of removing specific dose and duration targets for opioids.

Contrary to public perception, the problem of misuse, abuse, and diversion of prescription opioids has been much less of a factor in recent years than illicit opioids. A picture of a bottle of prescription painkillers often accompanies articles on drug overdose deaths, which creates an erroneous impression. Heroin and illicit synthetic fentanyl account for the vast majority of drug overdose-related fatalities, with fentanyl being far and away the biggest driver.

Nevertheless, there’s no denying that prescription opioids can be misused, abused, and diverted. Therefore, it is important to offer patients non-opioid prescription alternatives where appropriate.

The revised CDC guidelines include recommendations that doctors “optimize the use of non-opioid therapies,” and “consider opioids for pain only if benefits outweigh risks.”

Correspondingly, federal agencies have called for the development and launch of non-opioid alternatives for pain management. The Food and Drug Administration, for instance, has been taking steps aimed at fostering the development of non-addictive alternatives to opioids to manage acute pain. The agency issued draft guidance to provide recommendations to companies developing non-opioid analgesics for acute pain lasting up to 30 days. However, such treatments face considerable clinical and reimbursement challenges.

Drug manufacturers have been beset by a host of clinical development issues. To illustrate, while Vertex’s non-opioid pill has shown promise in a Phase 2 trial, others have failed, including Acadia’s investigational treatment, as well as Biogen‘s.

Perhaps the most conspicuous example of a non-opioid that was initially considered to have substantial potential, but later turned out to be plagued by development problems, is tanezumab. Tanezumab was an investigational nerve growth factor inhibitor. At one time, the biologic was deemed to be a promising non-opioid treatment for moderate-to-severe osteoarthritis pain in adults for whom the use of other analgesics is ineffective or inappropriate.

While tanezumab demonstrated some pain relief benefit in several trials, the drug has experienced safety issues over more than a decade of clinical development. The associated risk for joint destruction or rapidly progressive osteoarthritis is considered particularly worrisome. Moreover, a document published by the FDA stated there is “no convincing evidence” that tanezumab is more effective than painkillers like ibuprofen. Last year, a joint FDA advisory committee rejected a risk mitigation proposal for Pfizer and Eli Lilly’s osteoarthritis drug tanezumab, concluding that the drug’s safety risk to patients is too high. Subsequently, Pfizer and Lilly halted development of tanezumab.

Then, for those non-opioid treatments that do make it past the regulatory approval stage, there are reimbursement hurdles erected by insurers.

A 2018 Department of Health and Human Services report from the Pain Management Best Practices Inter-Agency Task Force on gaps in pain treatment concluded that insurers often don’t pay for non-opioid therapies that are more expensive than (generic) opioids. The trade group America’s Health Insurance Plans countered by saying that the report oversimplified the issue. The large insurer UnitedHealthcare went further by stating that the task force must not recommend broader reimbursement for pain non-opioid treatment and management.

Though insurers pushed back against the report’s main findings, they didn’t deny not covering non-opioid pain management therapies in at least some instances. Moreover, for many years, payers favored certain generic prescription opioids over alternative treatments, as can be inferred from publicly available lists of covered pain medications and their formulary positioning.

In the post-operative pain market, there are several non-opioid pain treatments, such as Exparel (bupivacaine liposome) and Zynrelef (bupivacaine/meloxicam). But, payers often assign these products a non-preferred spot on the formulary, or exclude them altogether. Moreover, acupuncture and other alternative methods to alleviate pain face high reimbursement hurdles.

A proposed bill which has bipartisan support, the Non-Opioids Prevent Addiction in the Nation (NOPAIN) Act (S. 586/H.R. 3259), is intended to ensure that every Medicare beneficiary has adequate access to safe, effective non-opioid drugs and devices by removing reimbursement barriers to opioid alternatives. Perhaps this will lead to changes in payer coverage in the public sector.

There are indeed opportunities to recalibrate the role of prescription opioids in pain management, while, where appropriate, expanding access to non-opioid alternatives. For this to happen, drugs in development will have to attain a better efficacy and safety profile. And, as for approved products, payers must implement more accommodating coverage and reimbursement policies.