Last reviewed 2026-05-13 · How we verify

High Dose ALKS 5461

Alkermes, Inc. · Phase 3 active Small molecule

High Dose ALKS 5461 is a Opioid receptor partial agonist / antagonist combination Small molecule drug developed by Alkermes, Inc.. It is currently in Phase 3 development for Major depressive disorder (Phase 3), Opioid use disorder (earlier development stage). Also known as: ALKS 5461.

ALKS 5461 is a combination of buprenorphine and samidorphan that acts as a partial mu-opioid receptor agonist while blocking opioid-induced side effects through antagonism at the opioid receptor.

ALKS 5461 is a combination of buprenorphine and samidorphan that acts as a partial mu-opioid receptor agonist while blocking opioid-induced side effects through antagonism at the opioid receptor. Used for Major depressive disorder (Phase 3), Opioid use disorder (earlier development stage).

Likelihood of approval

55.3% vs 58.3% industry baseline

If approved by FDA: likely 2028–2030

Steps remaining: NDA/BLA submission

Confidence: High

Why this estimate

Baseline phase 3 → approval rate +58.3pp
Industry-wide phase 3 drugs reach approval ~58.3% of the time (BIO/Informa 2023 industry benchmark across all therapeutic areas).
CNS / neurology attrition -3.0pp
CNS drugs have historically high Phase 3 failure rates (notably in Alzheimer disease + major depression).

Predicted approval windows by jurisdiction (conditional on FDA approval)

Regulator	Country	Likely year	Lag vs FDA
FDA	US	2028–2030	—
EMA	EU	2029–2031	+0.7 yr
MHRA	GB	2029–2031	+0.7 yr
Health Canada	CA	2029–2032	+0.9 yr
TGA	AU	2029–2032	+1.2 yr
PMDA	JP	2029–2032	+1.5 yr
NMPA	CN	2030–2033	+2.3 yr
MFDS	KR	2029–2032	+1.4 yr
CDSCO	IN	2029–2033	+1.8 yr
ANVISA	BR	2030–2033	+2.3 yr

Hover any row for the lag rationale. Lag estimates are reduced when the drug has FDA Breakthrough or EMA PRIME designation (sponsors file globally in parallel).

Estimate based on the BIO/Informa industry phase transition rates plus per-drug modifiers for therapeutic area, sponsor type, FDA designations, mechanism, and trial design. Per-jurisdiction lags from Tufts CSDD international approval studies. Not investment, clinical or regulatory advice. Methodology: /methodology#likelihood.

At a glance

Generic name	High Dose ALKS 5461
Also known as	ALKS 5461
Sponsor	Alkermes, Inc.
Drug class	Opioid receptor partial agonist / antagonist combination
Target	Mu-opioid receptor (partial agonist via buprenorphine; antagonist via samidorphan)
Modality	Small molecule
Therapeutic area	Pain Management / Psychiatry
Phase	Phase 3

Mechanism of action

ALKS 5461 combines buprenorphine, a partial mu-opioid receptor agonist used for pain and opioid use disorder, with samidorphan, an opioid antagonist. The samidorphan component is designed to mitigate certain opioid-related adverse effects such as respiratory depression, constipation, and abuse potential while maintaining the therapeutic benefits of buprenorphine. This combination approach aims to improve the safety and tolerability profile of opioid therapy.

Approved indications

Major depressive disorder (Phase 3)
Opioid use disorder (earlier development stage)

Common side effects

Nausea
Headache
Dizziness
Constipation
Sedation

Key clinical trials

Primary sources

Every claim on this page is sourced from regulatory or scientific primary sources. See our editorial policy for full methodology.

Source	Used for
ClinicalTrials.gov	Trial enrolment, design, endpoints, results

Competitive intelligence

For the full competitive landscape — auto-detected comparators, recent regulatory actions across the set, upcoming PDUFA, patent timeline, sponsor landscape:

High Dose ALKS 5461 CI brief — competitive landscape report
High Dose ALKS 5461 updates RSS · CI watch RSS
Alkermes, Inc. portfolio CI

Frequently asked questions about High Dose ALKS 5461

What is High Dose ALKS 5461?

High Dose ALKS 5461 is a Opioid receptor partial agonist / antagonist combination drug developed by Alkermes, Inc., indicated for Major depressive disorder (Phase 3), Opioid use disorder (earlier development stage).

How does High Dose ALKS 5461 work?

ALKS 5461 is a combination of buprenorphine and samidorphan that acts as a partial mu-opioid receptor agonist while blocking opioid-induced side effects through antagonism at the opioid receptor.

What is High Dose ALKS 5461 used for?

High Dose ALKS 5461 is indicated for Major depressive disorder (Phase 3), Opioid use disorder (earlier development stage).

Who makes High Dose ALKS 5461?

High Dose ALKS 5461 is developed by Alkermes, Inc. (see full Alkermes, Inc. pipeline at /company/alkermes-inc).

Is High Dose ALKS 5461 also known as anything else?

High Dose ALKS 5461 is also known as ALKS 5461.

What drug class is High Dose ALKS 5461 in?

High Dose ALKS 5461 belongs to the Opioid receptor partial agonist / antagonist combination class. See all Opioid receptor partial agonist / antagonist combination drugs at /class/opioid-receptor-partial-agonist-antagonist-combination.

What development phase is High Dose ALKS 5461 in?

High Dose ALKS 5461 is in Phase 3.

What are the side effects of High Dose ALKS 5461?

Common side effects of High Dose ALKS 5461 include Nausea, Headache, Dizziness, Constipation, Sedation.

What does High Dose ALKS 5461 target?

High Dose ALKS 5461 targets Mu-opioid receptor (partial agonist via buprenorphine; antagonist via samidorphan) and is a Opioid receptor partial agonist / antagonist combination.

Drug class: All Opioid receptor partial agonist / antagonist combination drugs
Target: All drugs targeting Mu-opioid receptor (partial agonist via buprenorphine; antagonist via samidorphan)
Manufacturer: Alkermes, Inc. — full pipeline
Therapeutic area: All drugs in Pain Management / Psychiatry
Indication: Drugs for Major depressive disorder (Phase 3)
Indication: Drugs for Opioid use disorder (earlier development stage)
Also known as: ALKS 5461

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing