Sat Dec 02, 2017 4:55 pm
The U.S. Food and Drug Administration today approved Sublocade, the first once-monthly injectable buprenorphine product for the treatment of moderate-to-severe opioid use disorder (OUD) in adult patients who have initiated treatment with a transmucosal (absorbed through mucus membrane) buprenorphine-containing product. It is indicated for patients that have been on a stable dose of buprenorphine treatment for a minimum of seven days.
Buprenorphine for the treatment of OUD is currently approved to administer as a tablet or film that dissolves in the mouth, or as an implant. Sublocade provides a new treatment option for patients in recovery who may value the benefits of a once-monthly injection compared to other forms of buprenorphine, such as reducing the burden of taking medication daily as prescribed (medical adherence). An independent FDA advisory committee supported the approval of Sublocade at a meeting held last month.
"Given the scale of the opioid crisis, with millions of Americans already affected, the FDA is committed to expanding access to treatments that can help people pursue lives of sobriety. Everyone who seeks treatment for opioid use disorder deserves the opportunity to be offered the treatment best suited to the needs of each individual patient, in combination with counseling and psychosocial support, as part of a comprehensive recovery plan,” said FDA Commissioner Scott Gottlieb, M.D. “As part of our ongoing work in supporting the treatment of those suffering from addiction to opioids, the FDA plans to issue guidance to expedite the development of new addiction treatment options. We’ll continue to pursue efforts to promote more widespread use of existing, safe and effective FDA-approved therapies to treat addiction.”
Improving access to prevention, treatment and recovery services, including the full range of medication-assisted treatments (MAT), is a focus of the FDA’s ongoing work to reduce the scope of the opioid crisis and one part of the U.S. Department of Health and Human Services’ Five-Point Strategy to Combat the Opioid Crisis.
OUD is the diagnostic term used for a chronic neurobiological disease characterized by a problematic pattern of opioid use leading to significant impairment or distress and includes signs and symptoms that reflect compulsive, prolonged self-administration of opioid substances for no legitimate medical purpose or, if another medical condition is present that requires opioid treatment, the opioid is used in doses far greater than the amount needed for treatment of that medical condition.
MAT is a comprehensive approach that combines approved medications (currently, methadone, buprenorphine or naltrexone) with counseling and other behavioral therapies to treat patients with OUD. 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 decreases the pleasurable effects of other opioids, making continued opioid abuse less attractive. According to the Substance Abuse and Mental Health Services Administration, patients receiving MAT for their OUD cut their risk of death from all causes in half.
Sublocade should be used as part of a complete treatment program that includes counseling and psychosocial support. Sublocade is a drug-device combination product that utilizes buprenorphine and the Atrigel Delivery System in a pre-filled syringe. It is injected by a health care professional (HCP) under the skin (subcutaneously) as a solution, and the delivery system forms a solid deposit, or depot, containing buprenorphine. After initial formation of the depot, buprenorphine is released by the breakdown (biodegradation) of the depot. In clinical trials, Sublocade provided sustained therapeutic plasma levels of buprenorphine over the one-month dosing interval.
The safety and efficacy of Sublocade were evaluated in two clinical studies (one randomized controlled clinical trial and one open-label clinical trial) of 848 adults with a diagnosis of moderate-to-severe OUD who began treatment with buprenorphine/naloxone sublingual film (absorbed under the tongue). Once the dose was determined stable, patients were given Sublocade by injection. A response to MAT was measured by urine drug screening and self-reporting of illicit opioid use during the six-month treatment period. Results indicated that Sublocade-treated patients had more weeks without positive urine tests or self-reports of opioid use, and a higher proportion of patients had no evidence of illicit opioid use throughout the treatment period, compared to the placebo group.
The most common side effects from treatment with Sublocade include constipation, nausea, vomiting, headache, drowsiness, injection site pain, itching (pruritus) at the injection site and abnormal liver function tests. The safety and efficacy of Sublocade have not been established in children or adolescents less than 17 years of age. Clinical studies of Sublocade did not include participants over the age of 65.
The FDA is requiring postmarketing studies to assess which patients would benefit from a higher dosing regimen, to determine whether Sublocade can be safely initiated without a dose stabilization period of sublingual buprenorphine, to assess the feasibility of administering Sublocade at a longer inter-dose interval than once-monthly and to determine a process for transitioning patients with long-term stability on a transmucosal buprenorphine dose to a monthly dose of Sublocade without the use of a higher dose for the first two months of treatment (loading dose).
Sublocade has a boxed warning that provides important safety information, including the risks of intravenous self-administration. If the product were to be administered intravenously rather than subcutaneously, the solid mass could cause occlusion (blockage), tissue damage or embolus (solid material that is carried in the blood and can become lodged in a blood vessel, which can lead to death). Sublocade must be prescribed and dispensed as part of a Risk Evaluation and Mitigation Strategy (REMS) to ensure that the product is not distributed directly to patients. Sublocade will be provided to HCPs through a restricted program, administered only by HCPs in a health care setting, and will require health care settings and pharmacies that dispense Sublocade to complete an enrollment form attesting that they have procedures in place to ensure that Sublocade is dispensed only to HCPs and not directly to patients.
The FDA granted this application Priority Review and Fast Track designations.
The FDA granted the approval of Sublocade to Indivior Inc.
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.
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TREATMENT BY INJECTION: DEALING WITH YOUR OST ONCE A MONTH?
Imagine only having to deal with your Opiate Substitution Therapy (OST) once a month. The Langton Centre in Surry Hills is part of an international trial of a new, long-acting depot buprenorphine product that can be given with a single subcutaneous injection once a month. No more queues, no more dealing with the daily grind.
Professor Nick Lintzeris who heads up Drug Health Services in South East Sydney Local Health District told UN: “This product will totally change the face of OST in Australia. It’s the biggest thing to happen since buprenorphine was introduced here nearly 20 years ago.”
Prof Lintzeris tells us “These monthly injections will not be for everyone. Patients who need regular support and care or take daily mental health medications with their OST may be better off with a closer relationship to their clinic or pharmacy. But for part of the OST community, the choice to be dosed with buprenorphine only once a month will be a very useful and welcome addition to the range of treatments available for opiate use. Once this new product is approved, there will be a freer life waiting for those who want it.”
The idea of only being dosed once a month certainly unlocks those “liquid handcuffs”. You can now take that job that requires travel, be it airline steward or truckie, without worrying about your dose. If you want to go on holidays there is no fussing with takeaway approvals or transfers. You could even go to countries that frown on OST for as long as a month without having to declare any medications. And for those looking towards abstinence, getting out of the habit of daily dosing helps put their drug use “out of sight out of mind”.
It is also possible the monthly injections may become popular in jail settings, solving some of the issues that limit the number of inmates who are granted OST.
The buprenorphine injection has no naloxone added. Those who choose to inject illicit drugs on top of their monthly injection will find it similar to injecting on top of methadone: they will feel a blunted effect but will not go into precipitated withdrawal.
Prof Lintzeris thinks it will still be 12 to 24 months before the product is on the standard menu here. The approval processes are strict - just as we want them to be. There are two companies ‘neck and neck’ in the race to have their product approved in the US, after which we hope they will tackle the Australian regulations.
Neither product has a market name yet, but for trial purposes are known as CAM2038 (from Braeburn Pharmaceuticals and Camurus) and RB6000 (from Indivior, makers of Subutex and Suboxone).
CAM2038 looks to be more flexible with four different dose strengths for either weekly or monthly injections. By contrast, RB6000 comes in only two doses: high (aiming for blockade effects) and low doses with only a monthly option. Unfortunately, it’s not simply a matter of choosing the best fit – as with many innovations one of these product will probably become standard and corner the market.
At this stage both products have had “double blind” tests (where the product is compared to a placebo or active control group of people on sublingual buprenorphine) with good results, although these studies are yet to be published. Langton is currently one of 4 Australian sites trialling CAM2038 as part of a year-long international trial of 20 sites to ensure the product is safe and workable. Professor Lintzeris reports that clinically all is going well with the trial at Langton. The product is easy to use, it’s flexible, no serious side effects and there appears to be high levels of consumer and staff satisfaction with the product.
The new injections bring advantages, but also challenges for its users. For example as we would not handle the product we wouldn’t be able to share with a needy partner or friend or put any aside for a rainy day. We also need to watch out that this new format is an addition and not a replacement to the current OST menu.
Right now, Australians can be prescribed an entire month’s worth of Suboxone film, yet this option is rarely taken up. This may be because few prescribing doctors or people who use drugs are aware of the option. Prof Lintzeris said “We need better continuing education so that doctors are up on new developments in OST.”
Those people prescribed monthly Suboxone often face costs out of proportion with the service they receive. Many pharmacists charging the same for a single monthly box of medication as for monthly daily dosing. “Section 85” prescribing would allow for a PBS listing, allowing users to pay a monthly cost of just over $6.20 for Health Care Card holders and $38.80 for the waged. It is the responsibility of the pharmaceutical company to apply for recategorising, however we are still waiting.
An additional reason few doctors write monthly prescriptions of Suboxone lies in stigma and discrimination. Doctors often do not trust their patients with a month of medication, believing it may be diverted or lost.
Monthly injections may solve some of these issues - but not if the cost is that we lose other choices. The control we gain by being free from day to day dosing hassles must be weighed carefully against the lack of control we lose by not being able to manage our medication ourselves. And because we are all different, with different needs, any new modes of OST must be additions and not replacements to the status quo. We will always welcome another option to the menu of treatment services.