Braeburn asks FDA to revoke Sublocade's orphan designation

Braeburn, which makes Brixadi, a buprenorphine injection, has filed a Citizen Petition calling on the Food and Drug Administration (FDA) to revoke “orphan designation” — exclusivity — for Sublocade, Indivior's injectable buprenorphine. Saying that unless the FDA does this, no competitive buprenorphine opioid use disorder (OUD) treatment will enter the market until 2024, Braeburn said the Orphan Drug Act was enacted to treat rare conditions with small patient populations. In some cases, the act is utilized even if a large population could benefit, if there is “no reasonable expectation” of recovering developing and marketing costs. Indeed, orphan drug designation (ODD) was granted to Subutex (buprenorphine) in 1994, when Indivior's predecessor was the sponsor. Now the FDA has “grandfathered” the Subutex designation to Sublocade “simply because the developer of Subutex and Sublocade is the same,” according to a press statement from Braeburn released earlier this month.     

Briefly Noted

We asked Jerry Rhodes, former top executive at CRC (now Acadia) and a leader in opioid treatment program management, what he thinks of methadone as a medication to be used in primary care to treat opioid use disorder (OUD), as some people — including former Office of National Drug Control Policy Director Michael Botticelli — recommended last year (see ADAW, July 16, 2018). “I take issue with that,” said Rhodes. “Methadone is a dangerous drug in an unregulated environment,” he told ADAW. Buprenorphine is prescribed this way, but “buprenorphine is a relatively safe drug, and methadone isn't,” he said. A veteran of many battles over methadone, including the near‐elimination of opioid treatment programs, Rhodes told ADAW that “you don't give unfettered access to methadone” to patients with OUD. “Be careful what you wish for” is his advice. This has the potential to cause harm, he said. “Only people who don't understand the history of its utilization would recommend this.”     

Fiellin: Keep the prescriber training for buprenorphine

It seems that almost everyone wants to deregulate buprenorphine for opioid use disorder (OUD) — with proposed legislation focused on getting rid of the Drug Addiction Treatment Act of 2000 (DATA 2000) waiver altogether (see ADAW, Oct. 11, “Bill to deregulate buprenorphine raises concerns among OTPs,” https://onlinelibrary.wiley.com/doi/10.1002/adaw.32510 ).     

Briefly Noted

Last week, Scott Gottlieb, M.D., abruptly and surprisingly resigned as commissioner of the Food and Drug Administration (FDA). He has pushed to reduce teenage vaping, been a vociferous supporter of medications to treat opioid use disorder and is noted in the field for his recommendation that methadone and buprenorphine patients should not be terminated from care for use of benzodiazepines. After he announced his resignation on March 5, vaping stocks surged. He was viewed as critical to protecting youths against nicotine and e‐cigarettes. “He was remarkably successful at keeping the agency moving forward at a difficult time and really focused on public health challenges, including the opioid epidemic and drug prices,” said Joshua M. Sharfstein, M.D., a former principal deputy commissioner at the FDA during the Obama administration, who is now a professor of health policy at the Johns Hopkins Bloomberg School of Public Health, told The New York Times. “He surprised a lot of people in his willingness to take some risks for public health.”     

‘Cash‐only’ buprenorphine a threat to opioid crisis

In an editorial written by the principal researcher on the clinical trials that led to the approval of buprenorphine‐naloxone to treat opioid use disorder, the increase in cash‐only buprenorphine clinics is called a threat to the opioid treatment system. “Proliferation of Cash‐Only Buprenorphine Treatment Clinics: A Threat to the Nation's Response to the Opioid Crisis,” by Art Van Zee, M.D., of the St. Charles Clinic, Stone Mountain Health Services, and David Fiellin, M.D., of the Yale University School of Medicine, was published in the March issue of the American Journal of Public Health.     

NJ governor approves medical cannabis for OUD

Last week, Gov. Phil Murphy announced that New Jersey would remove prior authorization for Medicaid for medication‐assisted treatment (MAT) and would approve opioid use disorder as an eligible indication for medical marijuana. The moves, among several announced Jan. 23 in the state's efforts to combat the opioid epidemic, would increase access to treatment. Last year, more than 3,000 individuals in the state died from overdoses. “The opioid epidemic continues to devastate families and communities across our state,” said Gov. Murphy. “As we combat this crisis, it is critical that we use data‐driven, evidence‐based strategies to support individuals suffering from addiction and help them get on the path to recovery.”     

Briefly Noted

A federal audit of opioid treatment programs (OTPs) — methadone clinics — in New York City found that of 115 random sample claims, 35 did not comply with Medicaid requirements, and that of 598 claims in a non‐random sample, 299 were billed in error. Extrapolating these errors, the federal Department of Health and Human Services (HHS) says the state improperly claimed at least $39.3 million in the federal share of Medicaid reimbursement, and owes that money back. Improper claims were mainly due to failure to record patients in the central registry, which exists to make sure patients aren't enrolled in multiple OTPs (18 of the 35 noncompliant claims). This was not an audit alleging fraud. Extrapolation as an accounting method for OTPs, where patients often come in every day, so that each patient has more than 300 claims a year, is questionable, but OTPs are used to this even in state audits. In other words, one OTP patient comes in six days a week, with six claims, and the database balloons. “You're extrapolating over our universe, and our universe becomes large because people come in for medication,” said Allegra Schorr, president of the Coalition of Medication‐Assisted Treatment Providers and Advocates, a New York–based membership organization, and board member of the American Association for the Treatment of Opioid Dependence. “When you're just trying to get money, this counts,” said Schorr. “They hit the lottery when it comes to an audit because of that extrapolation.” However, Schorr, who is also an owner and vice president of West Midtown Medical Group, a Manhattan‐based group that was the first OTP to dispense buprenorphine in New York state, stresses that compliance is always important. “It's critical that there is oversight,” she told ADAW. Meanwhile, the state is reviewing the audit and will respond. “The Office of Addiction Services and Supports (OASAS), in partnership with the NYS Office of Medicaid Inspector General, intends to review the specific findings of this audit cited by OIG [Office of Inspector General] to verify its accuracy and to determine an appropriate course of action,” said Evan Frost, spokesman for OASAS. “As a proactive measure, we will remind our OTP providers of their obligations to comply with state and federal laws and rules for providing and claiming Medicaid reimbursement and ensuring the quality of care for those receiving OTP services.” OA SAS regulates OTPs in the state. For the audit, go to https://oig.hhs.gov/oas/reports/region2/21701021.pdf     

Briefly Noted

Last month, the federal Food and Drug Administration (FDA) warned that combining gabapentin or pregabalin with central nervous system (CNS) depressants such as opioids could result in serious breathing problems for patients with underlying respiratory problems, or in the elderly. New labeling will be required on gabapentin and pregabalin, the FDA said. There is less evidence supporting such a risk in otherwise healthy people, the FDA said in the Dec. 19, 2019, warning. Gabapentin, first approved in 1993, is not a controlled substance. It is approved to treat various conditions, including seizures, nerve pain, fibromyalgia and restless legs syndrome. Pregabalin, first approved in 2004, is Schedule V on the Controlled Substances Act, the lowest‐risk category of controlled substance. “With the evolution of the opioid crisis, getting ahead of new concerns or addressing those that are already evident requires examining signs of misuse and abuse as soon as any signal emerges,” said Douglas Throckmorton, M.D., deputy director for regulatory programs in the FDA's Center for Drug Evaluation and Research, in announcing the warning. “Reports of gabapentinoid abuse alone, and with opioids, have emerged and there are serious consequences of this co‐use, including respiratory depression and increased risk of opioid overdose death. In response to these concerns, we are requiring updates to labeling of gabapentinoids to include new warnings of potential respiratory depressant effects.” Drug manufacturers are also being required to conduct clinical trials to evaluate the abuse potential of all gabapentinoids, particularly when combined with opioids, said Throckmorton. The downside is that prescribers could inadvertently increase opioid use by not using these medications, Throckmorton acknowledged, saying “we do not want to unintentionally increase opioid use by turning prescribers away from this class of pain medications.” For more information, go to https://www.fda.gov/drugs/drug‐safety‐and‐availability/fda‐warns‐about‐serious‐breathing‐problems‐seizure‐and‐nerve‐pain‐medicines‐gabapentin‐neurontin .     

Treatment center sues Tennessee town over zoning ordinance

Last week, ReVIDA Recovery Centers, which provides medication‐assisted treatment for opioid use disorder, announced that it would sue to keep its treatment program in Morristown, Tennessee, where the city has denied the company based on zoning. “Our patients are our first priority,” said CEO Lee Dilworth on September 25.     

Briefly Noted

Clayton Stafford died after using Vivitrol, and his family is suing Alkermes, the manufacturer, saying that the medication doesn't adequately treat addiction, compared to buprenorphine and methadone, and that the manufacturer knew this. In the lawsuit, California‐based law firm Lieff Cabraser alleges that Stafford, his parents and his treatment providers were misled into thinking Vivitrol was an appropriate treatment for his opioid use disorder. “Clayton Stafford's tragic death could have been avoided,” notes Lieff Cabraser partner Fabrice N. Vincent, who filed the lawsuit on behalf of the Stafford family. “The well‐reported defects in Vivitrol made Clayton's overdose a near‐foregone conclusion, and had the Staffords received accurate information about Vivitrol's risks and effective deficiencies from Alkermes, they would never have consented to its use by Clayton.” Naltrexone doesn't work to treat addiction and cravings, but just to block the effects of opioids, according to the lawsuit (and many others agree with this). “Because the patient's addiction is not adequately treated, the patient requires indefinite Vivitrol use to merely block the euphoric effects and keep the patient from seeking opiates,” Vincent said. “Patients therefore remain highly likely to relapse despite indefinite use of Vivitrol.” The lawsuit also makes note of Alkermes' direct‐to‐consumer marketing campaign, which extended into influencing the criminal justice system to use Vivitrol. Stafford had been mandated to use Vivitrol. Last year, the Food and Drug Administration issued a warning letter to Alkermes stating that its advertising did not state that stopping Vivitrol can lead to relapse and overdose, as is clearly stated by the label and package insert (see “FDA warns Alkermes about OD risk on Vivitrol ads,” ADAW, Dec. 16, 2019, https://onlinelibrary.wiley.com/doi/10.1002/adaw.32566 ).     

Correction

In “Is naloxone really needed in buprenorphine product?” (ADAW, June 10), there is an error. The sentence reading “But it is known that naloxone, an opioid antagonist (it is the active ingredient of Vivitrol)…” should have read “But it is known that naloxone, an opioid antagonist (it is the active ingredient of Narcan).…” We regret the error.     

Views on medication's role in treatment begin to converge amid deadly epidemic

In “Intervention stigma: How medication‐assisted treatment marginalizes patients and providers,” a researcher writes about one of the biggest paradoxes facing those treating and being treated for opioid use disorders (OUDs): the fact that the “gold standard” for treatment — methadone and buprenorphine — subjects both providers and patients to stigma, both within and outside addiction treatment communities.     

Aetna fined for parity violations in Pennsylvania

This month, Aetna was fined $190,000 for not complying with the federal Mental Health Parity and Addiction Equity Act. Specifically, the health insurer did not cover substance use disorder (SUD) and autism spectrum disorder as it was required to, according to a review by the Pennsylvania Department of Insurance. Aetna used “confusing policy language which could have led consumers to inaccurately believe they did not have coverage for certain substance use disorder services,” according to the insurance department. “While the department reviewed many priority areas through this examination, a significant focus was on the company's compliance with laws requiring parity of coverage for substance use disorders and mental health, which must be offered at the same level of benefits as medical or surgical treatment,” Pennsylvania Insurance Commissioner Jessica Altman said in a statement. She added, “Violations included incorrect application of copays, coinsurance and visit limits, as well as violations involving prior authorization for treatment and step therapy.”     

Briefly Noted

A report from the Substance Abuse and Mental Health Services Administration (SAMHSA) and the Centers for Disease Control and Prevention published in Drug and Alcohol Dependence this month, based on a national survey of 46 opioid treatment programs (OTPs), concludes that buprenorphine and Vivitrol are not given equal footing with methadone as medications used by OTPs. All three are approved by the Food and Drug Administration for the treatment of opioid use disorder. Barriers, including costs, are identified. In addition, the report charges that services for HPV, HIV and other infectious diseases are not adequately integrated into OTPs, and that the reach of OTPs should be expanded. The report, “Characteristics and Current Clinical Practices of Opioid Treatment Programs in the United States,” is by Christopher M. Jones and colleagues; Elinore F. McCance‐Katz, M.D., Ph.D., is the senior author.     

Pharmacy model for methadone,NAS link to demographics

In “Methadone Matters: What the United States Can Learn from the Global Effort to Treat Opioid Addiction,” senior author Jeffrey H. Sabet, M.D., and colleagues write about the lack of access to methadone treatment, in particular, for opioid use disorder (OUD) in the United States. They look at three pharmacy‐based models that exist in other countries. In their article, published online Feb. 6 in the Journal of General Internal Medicine, they promote the model of patients picking up methadone from pharmacies, as is done in, for example, Canada. The study was funded by the National Institute on Drug Abuse (NIDA) (from the United States) and cited by many as a call to reform the current opioid treatment program (OTP) system in the United States, where patients often prefer buprenorphine simply because they don't have to abide by methadone regulations.     

Briefly Noted

It's not every day that a nationally known “rehab” offers methadone. Recovery Centers of America (RCA) has opened its second medication‐assisted treatment (MAT) clinic — Bravo Medical — that does just this. “MAT is a vital tool in the battle against opioid addictions,” said Melissa Bishop, RCA national director of MAT, last week. “But many people are still afraid to learn more about it because of the stigma attached to this form of treatment.” The public is invited to tour the clinic on Oct. 16 from 12–2 p.m. At this event, families of loved ones from the southern New Jersey and Philadelphia area can tour the Somerdale, New Jersey, facility; see how medication is administered; and learn about the effectiveness of MAT. RCA offers MAT at its inpatient treatment centers and at stand‐alone MAT facilities such as Bravo Medical and the Trenton Healthcare Clinic. RCA offers methadone and buprenorphine. New Jersey State Medicaid is accepted at Bravo Medical and the Trenton Healthcare Clinic.     

ADA settlement exposes liability when providers refuse MAT patients

Gov. Andrew Cuomo of New York has added opioid use disorders (OUDs) to the list of approved conditions for which medical marijuana could be prescribed in the state, following the lead last month of New Jersey Gov. Phil Murphy, who limited such use as an “adjunct” to medications like methadone and buprenorphine (see ADAW, Jan. 28).     

Drug users who only need treatment should get it,not arrest and incarceration

Many changes at the local, state and federal levels have resulted in getting treatment to at least some people with opioid use disorder (OUD) in prisons and jails — treatment that just a few years ago would have been unthinkable in those very institutions. Lawsuits over inmate deaths have been followed by establishment of methadone and buprenorphine treatment in some locations, while others have been moving toward treatment as a matter of public policy, Paul Samuels, director and president of the Legal Action Center, told the attendees of the American Association for the Treatment of Opioid Dependence (AATOD) conference in Orlando, Florida, last month. He was joined by a jail accreditor, a sheriff and a judge at the plenary on corrections.