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

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.”     

FDA cracks down on CBD claims

Last week, the Food and Drug Administration (FDA) issued a warning letter to Curaleaf Inc. of Wakefield, Massachusetts, for illegally selling cannabidiol (CBD) with claims that their products treat cancer, Alzheimer's disease, opioid withdrawal, pain and “pet anxiety,” among other conditions and diseases.     

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 ).     

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.”     

States call on HHS to immediately change year‐1 bupe cap

A coalition of 22 states and territories is requesting that the federal Department of Health and Human Services (HHS) lift restrictions on providing buprenorphine, one of the only three federally approved medications to treat opioid use disorder (OUD). “Buprenorphine is an essential tool in the fight to end the opioid epidemic,” said Howard Zucker, M.D., commissioner of health for New York state, which is leading the initiative. “Removing federal restrictions on prescribing buprenorphine will ultimately save lives and eliminate unnecessary barriers that prevent people with opioid use disorder from having access to treatment,” he said.     

Cannabis and alcohol use in young adults: Connections

People with HIV, as well as those who are uninfected, do well on long‐term treatment with opioids (methadone or buprenorphine), researchers have found. There is a strong dose‐response relationship between mortality (all causes), unnatural death and overdose, with the higher morphine equivalent daily doses having the best outcomes, according to the study, by Ajay Manhapra, M.D., and colleagues and published online Sept. 16 in the Journal of Drug and Alcohol Dependence. “Opioid risk mitigation approaches should be expanded to address the potential effects of higher dose on all‐cause mortality in addition to unnatural and overdose fatalities,” the researchers conclude in the abstract. For the study, there were 22,996 patients on long‐term treatment, 6,578 (29%) with HIV and 16,418 (71%) uninfected. Among 5,222 (23%) deaths, 12% were unnatural deaths and 6% overdoses. The study, “All‐cause mortality among males living with and without HIV initiating long‐term opioid therapy, and its association with opioid dose, opioid interruption and other factors,” also found that benzodiazepine use was associated with overdose.     

Clarification on Braeburn's CAM2038/Brixadi/Buvidal

In our recent article “Sublocade: Why a placebo arm?” (see ADAW, March 11), we referred to the investigational medication CAM2038, an injectable (weekly subcutaneous depot) form of buprenorphine that is competing with Sublocade in the buprenorphine market. To make the terminology clear, the name of the investigational medication, developed by Braeburn in partnership with Camurus (Braeburn's European partner), is Brixadi. In Europe and Australia, however, the product is approved and marketed by Camurus under the trade name Buvidal. The Food and Drug Administration (FDA) granted tentative approval to Brixadi in December 2018, but Sublocade has exclusivity. “Brixadi's clinical development program was designed with input from the FDA,” said Sonnie Kim, Pharm.D., Braeburn vice president and head of medical affairs, in an email to ADAW. CAM2038 was found effective in Phase 2 research (see ADAW, June 26, 2017). The most recent results were published in JAMA Internal Medicine ( https://jamanetwork.com/journals/jamainternalmedicine/article‐abstract/2681061 ). We regret any confusion. For more information, go to www.braeburnrx.com .     

NIDA: How parents can talk to children about opioids

The National Institute on Drug Abuse (NIDA), part of the federal National Institutes of Health, has advice for parents in the midst of the opioid epidemic: “[T]alk openly about the effects of opioids and other drugs with your children and stay actively engaged in their lives.”     

DEA allows buprenorphine inductions based on telephone only

Last week, the Drug Enforcement Administration (DEA) said opioid treatment programs (OTPs) and Drug Addiction Treatment Act (DATA)–waived prescribers can treat new patients with buprenorphine based on a telephone call only. The Controlled Substances Act (CSA), enforced by the DEA, requires all new patients being treated with controlled substances to have an in‐person — or, for now, telemedicine — physical exam. Now, however, because of the coexisting COVID‐19 pandemic and opioid overdose crisis, the DEA has dropped this requirement. This follows the decision of the Substance Abuse and Mental Health Services Administration (SAMHSA) to allow exemptions from the OTP take‐home regulations allowing stable patients to be given 14 or 28 days of methadone doses, instead of coming in more frequently (see DEA, SAMHSA relax OTP/OBOT regulations due to COVID‐19, ADAW March 23, https://onlinelibrary.wiley.com/doi/10.1002/adaw.32664 ).     

More from Louis Baxter on doctors taking MAT

The question of whether or not doctors and other health care professionals on medication‐assisted treatment (MAT) are safe to practice medicine has been debated for the last few years since the advent of Food and Drug Administration (FDA)–approved MAT for opioid use disorder (OUD). The newly approved medications have been primarily buprenorphine formulations for OUD, naltrexone formulations for OUD and alcohol use disorder (AUD), and, most recently, an alpha 2‐adrenergic medication that specifically targets amelioration of opioid‐withdrawal symptoms from OUD (lofexidine). Quite frankly, the question of safety about medications to treat substance use disorder (SUD) has been asked since the development of methadone for OUD treatment more than 30 years ago.     

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.     

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.”     

DEA proposal for mobile methadone finally released

The federal Drug Enforcement Administration (DEA) has issued a long‐awaited proposed rule that would allow opioid treatment programs (OTPs) — treatment programs that use methadone — to transport the medication to patients via “conveyances” (such as vans). This means that patients would no longer have to go to the brick‐and‐mortar OTP.     

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.