Statement from FDA Commissioner Scott Gottlieb, M.D., on new steps to encourage more widespread innovation and development of new treatments for opioid use disorder

FDA Statement

• For Immediate Release: April 20, 2018

Addressing the issue of opioid misuse and abuse remains one of my highest priorities. This is the most profound public health crisis facing the U.S. Food and Drug Administration and Americans. The FDA remains committed to take steps across all of its authorities to make significant inroads against this tragic epidemic. As part of this effort, we are committed to take steps to help those currently addicted to opioids, while taking steps to help prevent new cases of addiction.

The unfortunate reality is millions of Americans are suffering from addiction to opioid drugs, and millions more live in fear that a friend or loved one could succumb to an overdose. Along with our colleagues across the Department of Health and Human Services, the FDA is working to break the cycle of opioid addiction.

One of the critical ways the FDA can play a role is by encouraging more widespread innovation and development of medication for use in medication-assisted treatments (MAT). There are currently three FDA-approved MAT drugs – methadone, buprenorphine and naltrexone – that have been demonstrated to be safe and effective in combination with counseling and psychosocial support to stabilize brain chemistry; reduce or block the euphoric effects of opioids; relieve physiological cravings; and normalize body functions. Yet, despite having these treatment options, we know more needs to be done. For example, we know that not every patient seeking treatment is offered all three of these options.

The decision for an individual to undergo treatment for OUD is often a complex and challenging one, and requires persistence to stay on course and on treatment. With tablets, for example, there may be the temptation to take an extra dose, or even share or sell it to those for whom it was not prescribed. And we also must confront the reality of what recovery means – is complete abstinence the only clinical endpoint appropriate to assess whether these medications are working?

Based on what we know of the biology of addiction, and its variability across individuals, we must explore other ways of measuring success. We must also make sure that health care providers understand the treatment options available for their patients, as well as the unique and complex considerations involved in treating those with a substance use disorder compared to other diseases. Medications currently approved to treat OUD do improve outcomes – such as decreasing opioid use and reducing relapse or overdose. But relapse rates are still high. And not all patients respond positively to such medications. The FDA recently published a paper with the National Institute on Drug Abuse that describes our efforts to overcome some of the barriers to new drug development and the issues with how we determine effectiveness.

With this understanding in mind, the FDA is working to ensure the availability of high-quality, effective treatments to facilitate the development of new MAT products, and new formulations of existing drugs that could have attributes that are better tailored to patient needs. Today, the FDA issued the first of two draft guidances as part of these important efforts.

These new guidance documents may ultimately lead to new treatments that improve outcomes for those struggling with an opioid addiction. The new draft guidance issued today, “Opioid Dependence: Developing Buprenorphine Depot Products for Treatment,” outlines the FDA’s current thinking about drug development and trial design issues relevant to the study of sustained-release “depot” buprenorphine products, which include modified-release products for injection or implantation. In addition, in the coming months, we will take additional steps, beyond these guidance documents, to help promote the development of better treatments for those suffering from opioid use disorder.

Regular adherence to MAT with buprenorphine reduces opioid withdrawal symptoms and the desire to use opioids, without causing the cycle of highs and lows associated with opioid misuse or abuse. At proper doses, buprenorphine also blocks the pleasurable effects of other opioids, making continued opioid abuse less attractive. By ensuring this blockade, more novel formulations or delivery mechanisms described in our guidance – including passive-compliance formulations such as sustained-release depots and implants – can provide effective treatment of opioid dependence, which may result in less misuse, abuse, diversion, or accidental exposure compared to self-administered formulations such as transmucosal tablets and films, which are absorbed through mucus membranes.

In particular, this draft guidance outlines possible ways companies can more efficiently explore innovations in buprenorphine products – from the data needed to support approval, to the specific review pathways that are available to help streamline how sponsors consider their development plans. The guidance details the types of studies the FDA recommends for depot buprenorphine products that are similar to an approved depot product, as well as depot buprenorphine products with novel features relative to approved depot products. For example, in some cases, companies developing new, longer-acting formulations of existing buprenorphine drugs may not need to do additional efficacy studies. The guidance also includes information on efficacy studies including trial design, recommended efficacy endpoints, and novel efficacy endpoints related to buprenorphine. Finally, we’ve also described the use of the 505(b)(2) regulatory pathway for product development programs. This can provide a more efficient development pathway. A proposed depot buprenorphine product may be similar to an approved drug in terms of exposure of the drug, but may have unique or novel characteristics (like a new type of delivery system or formulation) that make it ineligible to be a generic drug approved under an abbreviated new drug application. This guidance clarifies that such a product could be submitted in an application pursuant to section 505(b)(2) of the Federal Food, Drug, and Cosmetic Act, which can provide a more streamlined development path.

We hope the scientific and regulatory clarity provided helps increase the efficiency of developing more depot buprenorphine products to support this patient community. But as we’ve discussed, there’s a continued need to innovate treatment of opioid use disorder to provide patients with new, and better options. This is true, for example, when it comes to adequately incorporating the struggles faced by those with opioid addiction into drug development and review considerations. To these ends, the FDA recently held a Patient-Focused Drug Development meeting to gain feedback from patients. As part of this process, the agency is working on another draft guidance that will provide a framework for the development of novel clinical endpoints that can form the basis of additional MAT product approvals.

For example, one endpoint that’s relevant to the treatment of addiction is the craving that fuels continued drug use. Craving is an endpoint that the FDA has included in labeling for smoking cessation products. The FDA intends to provide assistance to develop a validated measurement of “craving” or “urge to use” illicit opioids to complement other endpoints and to determine how it supports the goal of sustained abstinence.

We welcome additional product development aimed at creating new treatments for OUD – and such therapies may qualify for the agency’s expedited review programs. These guidances are only one piece of our efforts to encourage more widespread innovation and access to treatments for OUD, and we believe these new guidances can help make the pathway for developing new MAT more efficient.

As we encourage the development new forms of MAT, and consider how the agency applies our benefit-risk assessment in our decision-making, it’s important that we understand the effect that opioid addiction has on patients’ day-to-day health and well-being; their experience using prescription medical treatments and other types of treatments or therapies; and challenges or barriers to accessing or using medical treatments for OUD.

It’s also critical that as we work to ensure physicians embrace rational prescribing practices when opioids are appropriate for treating pain, that they also have the tools necessary to spot signs of abuse and treat opioid use disorder with therapies such as buprenorphine. One way we’re doing that is through a recently revised Blueprint of the core content for training that opioid drug manufacturers are required to make available to prescribers.

The revised Blueprint broadens content to include information on acute and chronic pain management, safe use of opioids or other non-opioid or non-drug treatments, as well as material on addiction medicine and opioid use disorders. Once finalized later this year, together with the Opioid Analgesic Risk Evaluation and Mitigation Strategy (REMS), the Blueprint will apply to manufacturers of both immediate-release opioid analgesics intended for use in the outpatient setting and extended release/long-acting formulations. These measures are designed to directly target all health care professionals involved in patient care – prescribers, as well as nurses, pharmacists and physicians assistants – so that we change the culture of medicine around treating pain and better prevent new cases of addiction.

We’re also taking steps to tackle the unfortunate stigma that’s sometimes associated with MAT use. This stigma reflects a view some have: that a patient is still suffering from addiction even when they’re in full recovery, just because they require medication to treat their illness, craving and withdrawal symptoms. Addiction is defined as more than physical dependence; it often includes psychological craving and ongoing use despite harmful consequences. Among other effects, MAT can help manage these dangerous symptoms, which can in turn help prevent relapse and help return patients to their jobs and families. A patient can have a physical dependence to opioid replacement therapy to treat the symptoms of withdrawal; but is in full recovery and no loner suffers from an addiction to opioid medication.

Ultimately, it’s clear there are an urgent need to ensure access to, and wider use and understanding of, approved treatments. Unfortunately, I believe that far too few people who are addicted to opioids are offered an adequate chance for treatment that uses medications. More widespread adoption of MAT, coupled with relevant social, medical and psychological services, has the highest probability of being the most effective of all available treatments for OUD. Improving access to prevention, treatment and recovery services, including the full range of MAT, is a focus of the FDA’s ongoing work to reduce the scope of the opioid crisis and one part of HHS’ Five-Point Strategy to Combat the Opioid Crisis.

The FDA remains committed to addressing this national crisis on all fronts, with a significant focus on decreasing exposure to opioids and preventing new addiction; supporting the treatment of those with opioid use disorder; fostering the development of novel pain treatment therapies; and taking action against those who contribute to the illegal importation and sale of opioid products. The agency will also continue looking at how drugs that are already on the market are used, in both medical settings and also illicit ones, and take action where needed.

The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.