DUBLIN, Jan. 14, 2021 /PRNewswire/ -- Results from a
National Institute on Drug Abuse (NIDA)-funded study
evaluating the efficacy and safety of naltrexone for
extended-release injectable suspension (XR-NTX) administered once
every three weeks plus oral extended-release bupropion administered
daily as a combination treatment for adults with moderate or severe
methamphetamine use disorder (MUD) were published today by Dr.
Madhukar H. Trivedi et al. in the
New England Journal of Medicine
(NEJM).1 This is the second published study
evaluating this combination regimen for the treatment of
MUD.2
The number of adults living with MUD has risen in recent years.
In 2019, approximately 1 million adults in the U.S. reported having
a methamphetamine use disorder—an increase of more than 50 percent
since 2016.3 Currently, there are no FDA-approved
medicines for the treatment of MUD.
"Given the scale and severity of the methamphetamine epidemic in
the U.S., we applaud the clinical community's efforts and
commitment to advancing research focused on treatment options for
this critically underserved patient population," said Craig Hopkinson, M.D., Chief Medical Officer and
Executive Vice President of Research & Development at Alkermes.
"We're encouraged by the publication of this NIDA-funded study in
the New England Journal of Medicine, and plan to engage with
the FDA to better understand what options may exist for VIVITROL
with regards to these data."
VIVITROL® (naltrexone for extended-release injectable
suspension) is not approved for the treatment of MUD. VIVITROL,
developed by Alkermes (Nasdaq: ALKS), was approved by the U.S.
Food and Drug Administration (FDA) for the treatment of alcohol
dependence in 2006 and for the prevention of relapse to opioid
dependence, following opioid detoxification, in 2010. VIVITROL is
to be administered once every four weeks as part of a comprehensive
management program that includes psychosocial support.
About the ADAPT-2 Study
The "Accelerated Development
of Additive Pharmacotherapy Treatment (ADAPT-2) for Methamphetamine
Use Disorder" study was a multi-site, double-blind, 12-week
trial to evaluate the efficacy and safety of XR-NTX (380 mg every
three weeks) plus oral extended-release bupropion (450 mg/day) in
adults with moderate or severe MUD. Participants (N=403) with
moderate or severe MUD (defined as reported use on at least 18 of
the 30 days prior to randomization) were randomized to combination
therapy (XR-NTX, 380 mg IM every three weeks, plus bupropion XL, up
to 450 mg/d) versus placebo in a two-stage study. Placebo
non-responders from stage 1 (6 weeks) were re-randomized in stage 2
for another 6 weeks. The primary outcome was the proportion of
"responders," defined as having at least three
methamphetamine-negative urine samples out of four samples obtained
during weeks 5-6 (for stage 1) or weeks 11-12 (for stage 2).
Response rates were higher with XR-NTX plus bupropion than with
placebo across both stages (overall weighted treatment effect of
11.1 percentage points; Wald z-test statistic = 4.53; p < 0.001;
NNT =9), as well as in each stage [stage 1: (16.5% COMB vs. 3.4%
PBO); stage 2: (11.4% COMB vs. 1.8% PBO)]. Secondary outcomes also
favored treatment with XR-NTX plus bupropion XL as compared to
placebo. Adverse events in the combination treatment group included
gastrointestinal disorders, tremor, malaise, hyperhidrosis, and
anorexia. Serious adverse events occurred in 8 of 223 participants
(3.6%) who received XR-NTX plus bupropion in the study. Alkermes
provided XR-NTX and matched placebo free of charge for use in this
trial under a written agreement with NIDA.
About VIVITROL
VIVITROL® (naltrexone
for extended-release injectable suspension) is a once-monthly
medication for the treatment of alcohol dependence and for the
prevention of relapse to opioid dependence, following opioid
detoxification. Treatment with VIVITROL should be part of a
comprehensive management program that includes psychosocial
support. For more information, visit www.vivitrol.com.
About Alkermes
Alkermes plc is a fully integrated,
global biopharmaceutical company developing innovative medicines in
the fields of neuroscience and oncology. The company has a
portfolio of proprietary commercial products focused on addiction
and schizophrenia, and a pipeline of product candidates in
development for schizophrenia, bipolar I disorder,
neurodegenerative disorders, and cancer. Headquartered in
Dublin, Ireland, Alkermes plc has
an R&D center in Waltham,
Massachusetts; a research and manufacturing facility in
Athlone, Ireland; and a
manufacturing facility in Wilmington,
Ohio. For more information, please visit Alkermes' website
at www.alkermes.com.
IMPORTANT SAFETY INFORMATION
INDICATIONS
VIVITROL is indicated for:
- Treatment of alcohol dependence in patients who are able to
abstain from alcohol in an outpatient setting prior to initiation
of treatment with VIVITROL. Patients should not be actively
drinking at the time of initial VIVITROL administration.
- Prevention of relapse to opioid dependence, following opioid
detoxification.
- VIVITROL should be part of a comprehensive management program
that includes psychosocial support.
CONTRAINDICATIONS
VIVITROL is contraindicated in
patients:
- Receiving opioid analgesics
- With current physiologic opioid dependence
- In acute opioid withdrawal
- Who have failed the naloxone challenge test or have a positive
urine screen for opioids
- Who have exhibited hypersensitivity to naltrexone,
polylactide-co-glycolide (PLG), carboxymethylcellulose, or any
other components of the diluent
IMPORTANT SAFETY INFORMATION
WARNINGS AND
PRECAUTIONS
Vulnerability to Opioid Overdose:
- After opioid detoxification, patients are likely to have a
reduced tolerance to opioids. VIVITROL blocks the effects of
exogenous opioids for approximately 28 days after administration.
As the blockade wanes and eventually dissipates completely, use of
previously tolerated doses of opioids could result in potentially
life-threatening opioid intoxication (respiratory compromise or
arrest, circulatory collapse, etc.).
- Cases of opioid overdose with fatal outcomes have been reported
in patients who used opioids at the end of a dosing interval, after
missing a scheduled dose, or after discontinuing treatment.
Patients and caregivers should be told of this increased
sensitivity to opioids and the risk of overdose.
- Although VIVITROL is a potent antagonist with a prolonged
pharmacological effect, the blockade produced by VIVITROL is
surmountable. The plasma concentration of exogenous opioids
attained immediately following their acute administration may be
sufficient to overcome the competitive receptor blockade. This
poses a potential risk to individuals who attempt, on their own, to
overcome the blockade by administering large amounts of exogenous
opioids.
- Any attempt by a patient to overcome the VIVITROL blockade by
taking opioids may lead to fatal overdose. Patients should be told
of the serious consequences of trying to overcome the opioid
blockade.
Injection Site Reactions:
- VIVITROL must be prepared and administered by a healthcare
provider.
- VIVITROL injections may be followed by pain, tenderness,
induration, swelling, erythema, bruising, or pruritus; however, in
some cases injection site reactions may be very severe.
- In the clinical trials, one patient developed an area of
induration that continued to enlarge after 4 weeks, with subsequent
development of necrotic tissue that required surgical
excision.
- Injection site reactions not improving may require prompt
medical attention, including, in some cases, surgical
intervention.
- Inadvertent subcutaneous/adipose layer injection of VIVITROL
may increase the likelihood of severe injection site
reactions.
- Select proper needle size for patient body habitus, and use
only the needles provided in the carton.
- Patients should be informed that any concerning injection site
reactions should be brought to the attention of their healthcare
provider.
Precipitation of Opioid Withdrawal:
- When withdrawal is precipitated abruptly by administration of
an opioid antagonist to an opioid-dependent patient, the resulting
withdrawal syndrome can be severe. Some cases of withdrawal
symptoms have been severe enough to require hospitalization, and in
some cases, management in the ICU.
- To prevent occurrence of precipitated withdrawal,
opioid-dependent patients, including those being treated for
alcohol dependence, should be opioid-free (including tramadol)
before starting VIVITROL treatment:
-
- An opioid-free interval of a minimum of 7–10 days is
recommended for patients previously dependent on short-acting
opioids.
- Patients transitioning from buprenorphine or methadone may be
vulnerable to precipitated withdrawal for as long as two
weeks.
- If a more rapid transition from agonist to antagonist therapy
is deemed necessary and appropriate by the healthcare provider,
monitor the patient closely in an appropriate medical setting where
precipitated withdrawal can be managed.
- Patients should be made aware of the risk associated with
precipitated withdrawal and be encouraged to give an accurate
account of last opioid use.
- Precipitated opioid withdrawal has been observed in
alcohol-dependent patients in circumstances where the prescriber
had been unaware of the additional use of opioids or co-dependence
on opioids.
Hepatotoxicity:
- Cases of hepatitis and clinically significant liver dysfunction
have been observed in association with VIVITROL. Warn patients of
the risk of hepatic injury; advise them to seek help if
experiencing symptoms of acute hepatitis. Discontinue use of
VIVITROL in patients who exhibit acute hepatitis symptoms.
Depression and Suicidality:
- Alcohol- and opioid-dependent patients taking VIVITROL should
be monitored for depression or suicidal thoughts. Alert families
and caregivers to monitor and report the emergence of symptoms of
depression or suicidality.
When Reversal of VIVITROL Blockade Is Required for Pain
Management:
- For VIVITROL patients in emergency situations, suggestions for
pain management include regional analgesia or use of non-opioid
analgesics. If opioid therapy is required to reverse the VIVITROL
blockade, patients should be closely monitored by trained personnel
in a setting staffed and equipped for CPR.
Eosinophilic Pneumonia:
- Cases of eosinophilic pneumonia requiring hospitalization have
been reported. Warn patients of the risk of eosinophilic pneumonia
and to seek medical attention if they develop symptoms of
pneumonia.
Hypersensitivity Reactions including Anaphylaxis:
- Cases of urticaria, angioedema, and anaphylaxis have been
observed with use of VIVITROL in the clinical trial setting and in
postmarketing use.
- Patients should be warned of the risk of hypersensitivity
reactions, including anaphylaxis.
- In the event of a hypersensitivity reaction, patients should be
advised to seek immediate medical attention in a healthcare setting
prepared to treat anaphylaxis. The patient should not receive any
further treatment with VIVITROL.
Intramuscular Injections:
- As with any intramuscular injection, VIVITROL should be
administered with caution to patients with thrombocytopenia or any
coagulation disorder.
Alcohol Withdrawal:
- Use of VIVITROL does not eliminate nor diminish alcohol
withdrawal symptoms.
Interference with Laboratory Tests
- VIVITROL may be cross-reactive with certain immunoassay methods
for the detection of drugs of abuse (specifically opioids) in
urine.
- For further information, reference to the specific immunoassay
instructions is recommended.
ADVERSE REACTIONS
- The adverse events seen most frequently in association with
VIVITROL therapy for alcohol dependence (ie, those occurring in ≥5%
and at least twice as frequently with VIVITROL than placebo)
include nausea, vomiting, injection site reactions (including
induration, pruritus, nodules, and swelling), arthralgia,
arthritis, or joint stiffness, muscle cramps, dizziness or syncope,
somnolence or sedation, anorexia, decreased appetite or other
appetite disorders.
- The adverse events seen most frequently in association with
VIVITROL in opioid-dependent patients (ie, those occurring in ≥2%
and at least twice as frequently with VIVITROL than placebo) were
hepatic enzyme abnormalities, injection site pain, nasopharyngitis,
insomnia, and toothache.
You are encouraged to report side effects to the FDA.
Visit www.fda.gov/medwatch or call 1-800-FDA-1088.
Note Regarding Forward-Looking Statements
Certain
statements set forth in this press release constitute
"forward-looking statements" within the meaning of the Private
Securities Litigation Reform Act of 1995, as amended, including,
but not limited to, statements concerning: the potential
therapeutic and commercial value of XR-NTX plus bupropion as a
combination treatment for MUD; and the company's plans to engage
with the FDA regarding potential options for VIVITROL relating to
the ADAPT-2 data. You are cautioned that forward-looking statements
are inherently uncertain. Although the company believes that such
statements are based on reasonable assumptions within the bounds of
its knowledge of its business and operations, the forward-looking
statements are neither promises nor guarantees and they are
necessarily subject to a high degree of uncertainty and risk.
Actual results may differ materially from those expressed or
implied in the forward-looking statements due to various risks and
uncertainties. These risks and uncertainties include, among others,
whether the combination treatment of XR-NTX plus bupropion could be
shown to be unsafe or ineffective; whether clinical results for
this combination treatment will be predictive of results of future
clinical studies or real-world results; the outcome of interactions
with the FDA related to VIVITROL and the ADAPT-2 data; and those
risks and uncertainties described under the heading "Risk Factors"
in the company's Annual Report on Form 10-K for the year ended
Dec. 31, 2019, the company's
Quarterly Report on Form 10-Q for the quarter ended June 30, 2020 and in subsequent filings made by
the company with the U.S. Securities and Exchange Commission (SEC),
which are available on the SEC's website at www.sec.gov. Existing
and prospective investors are cautioned not to place undue reliance
on these forward-looking statements, which speak only as of the
date hereof. Except as required by law, the company disclaims any
intention or responsibility for updating or revising any
forward-looking statements contained in this press release.
VIVITROL® is a registered trademark
of Alkermes, Inc.
1 Trivedi MH, Walker R, Ling, W, et al.
Bupropion and Naltrexone in Methamphetamine Use Disorder. New
England Journal of Medicine, 2021;384:140-53. DOI:
10.1056/NEJMoa2020214
2 Mooney LJ, Hillhouse MP, Thomas C, et al. Utilizing
a Two-stage Design to Investigate the Safety and Potential Efficacy
of Monthly Naltrexone Plus Once-daily Bupropion as a Treatment for
Methamphetamine Use Disorder. Journal of Addiction
Medicine, 2016;10(4), 236–243.
https://doi.org/10.1097/ADM.0000000000000218
3 SAMHSA. Behavioral Health Trends in the United States: Results from the 2016 and
2019 National Surveys on Drug Use and Health. Accessed on
Jan. 12, 2021 from:
https://www.samhsa.gov/data/data-we-collect/nsduh-national-survey-drug-use-and-health.
Alkermes Contacts:
For Investors: Sandy Coombs, +1 781
609 6377
For Media: Marisa Borgasano, +1 781
609 6659
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