16 May Addressing the opioid crisis: abuse deterrent-formulations and the future of pain management
The opioid epidemic in the United States is a serious national crisis that affects public health as social and economic welfare. From 1999 to 2017, more than 700,000 people died from a drug overdose; of which, 218,000 were related to prescription opioid use/abuse.1 In 2017 alone, 47,000 of the 70,200 drug overdoses involved an opioid; on average, 130 Americans overdosed on opioids each day.1 That same year, approximately 1.7 million Americans suffered from opioid substance abuse disorder.2 The CDC estimates the economic burden of prescription opioid misuse including healthcare costs, addiction treatment, lost productivity and criminal justice resources to be $78.5B per year.2
Nearly a third of the people who are prescribed opioids will misuse them. About a third of those misusing opioids will form dependencies. Only a few people who develop opioid dependencies will go on to use heroin, though 80% of heroin users first misused prescription opioids.2
Figure 1: Use of opioids in patients prescribed opioids for chronic pain2
The national rate of opioid prescribing began steadily rising in 2006 due to an increase in the use of opioids for non-cancer chronic pain.8,21 Prescribing peaked in 2012 at 255,000,000 prescriptions, corresponding to 81.3 prescriptions per 100 Americans.21 The increased use of prescription opioids has been linked to a sharp increase in opioid-related drug overdoses over the past decade.7 Recent evidence shows no slowing of this trend; from July 2016 to September 2017, overdoses increased by 30% in 52 areas across 45 states.14
Figure 2: Age-adjusted drug overdose death rates by opioid category; US, 1999-20177
CMS reports the Medicaid and Medicare populations have the highest and fastest-growing prevalence of diagnosed opioid abuse, respectively.13 The Medicaid population generally has lower income and health status, along with more than twice the rate of mental health disorders than those with private insurance.8 By definition, the Medicare population is comprised of older individuals with an increased likelihood of having health conditions, including a higher prevalence of pain syndromes.8 The underlying characteristics of the Medicaid and Medicare populations help explain why the rates of opioid abuse in Medicaid and Medicare are higher and faster-growing, respectively, compared to rates seen in other insurance channels (i.e., private insurance). In 2016, 0.0087% of Medicaid beneficiaries and more than 0.006% of Medicare were diagnosed with opioid abuse disorder.15 This rate of opioid abuse among Medicaid beneficiaries is 10x higher than the rate among beneficiaries with private insurance coverage.15
Both the healthcare system and various governmental agencies are taking multiple approaches to address the opioid addiction epidemic and to bring overdose rates down. For example, the U.S. Department of Health and Human Services (HHS) has prioritized improving access to opioid misuse treatment and recovery services, promoted overdose-reversing drugs, improved public health surveillance, supported research on pain and addiction, and advocated for better pain management practices. Similarly, the National Institute of Health (NIH) is collaborating with pharmaceutical companies and academic research centers to develop safe, effective, and non-addictive strategies to manage chronic pain, promote innovative medications and technologies for opioid use disorders, and improve overdose prevention and reversal interventions.2 Furthermore, Congress recently passed legislation promoting biomedical research to find new non-addictive pain drugs.3
In parallel, the US Food and Drug Administration (FDA) is encouraging the development of prescription opioids with abuse-deterrent formulations (ADFs). For example, the FDA released 43 product-specific guidances to promote generic and ADF drug development.q ADFs are less susceptible to abuse because they target known or expected routes of abuse., such as crushing in order to snort or dissolving in order to inject.4 However, ADFs cannot prevent people from the most common route of abuse – taking more pills than prescribed.12 To date, there are no studies that compare rates of addiction in ADF versus non-ADF users.11 Since ADFs can gain approval based on the more abbreviated 505(b)(2) FDA approval pathway wherein they demonstrate highly similar efficacy and pharmacokinetics to reference drugs, clinical development often progresses directly from Phase I to Phase III, reducing total time to FDA approval.22 Since 2010, the FDA has approved over 10 ADF drugs such as OxyContin (2010) and Targiniq ER (2014).5,6
However, not all ADF opioids are available in the US market. For example, Teva’s received FDA approval in 2017 but Teva announced commercialization would not proceed in February 2018, at least partially due to pricing and market access challenges. Market access is one major hurdle for manufacturers as they seek to premium price ADFs relative to non-ADFs.3 Believing that new branded ADF opioids have more value and deserve premium pricing, ADF opioids typically cost 5-15x more than non-ADFs opioids, which are mostly low-cost generics.11 As a result, many insurance plans require prior authorization to reimburse ADF opioids, where no such requirement exists for cheaper non-ADFs. Prior authorizations and similar utilization management tools usually reduce prescribing and/or patient fulfillment and thus product revenue; this likely influenced Teva’s decision to not commercialize Vantrela.
In response, some states have enacted legislation to promote the use of ADFs. For example, in 2014, Massachusetts became the first state to pass legislation that requires pharmacies to substitute ADFs by default for chemically equivalent non-ADF opioid prescriptions unless specifically directed otherwise by the prescriber. The law also requires health insurers to cover these ADFs with no additional cost burden to patients.11 In addition, ADF opioid use is encouraged by the White House Office of National Drug Control Policy, the FDA, the CDC, Substance Abuse and Mental Health Services Administration, the National Institute of Drug Abuse, some states, and the DEA. However, many Medicare plans are not managing ADFs at parity to cheaper non-ADFs opioids due to cost. CMS has broad rules for Medicare and Medicaid formulary design which preclude direct management of ADFs. Instead, CMS addresses opioid misuse through other programs and initiatives.13 Examples of CMS activities include mandating patients use a single pharmacy or prescriber in order to better track opioid use, establishing quantity limits to ensure patients are not exceeding FDA recommended dosing, requiring prior authorizations to document physicians have assessed addiction risk and discussed a treatment plan with patients, and in some places (e.g., Vermont), stepping opioids through methadone.18-20
Currently, there are 8 approved ADFs, 12 ongoing and planned ADF opioids in industry-sponsored trials, and 175 non-opioid analgesics in clinical development for nociceptive or neuropathic pain. This balance suggests industry sees more value in non-opioids than ADF opioid formulations, which is likely related to the pricing and resulting market access challenges ADF opioids have faced to date. Without convincing data demonstrating ADF opioids are effective at reducing opioid dependence and addiction, many payers are simply not willing to pay a premium for ADFs. Unless manufacturers are able to demonstrate ADFs offer a clear benefit in reducing opioid dependence, the market will likely continue to shift towards non-opioid analgesics as well as expanding the use of multimodal and non-pharmacologic techniques for acute and chronic pain management.3
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- Datamonitor Report