buprenorphine/samidorphan (ALKS 5461) / Alkermes - LARVOL DELTA

The efficacy and safety of buprenorphine for the treatment of depression: A systematic review and meta-analysis. (PubMed, J Psychiatr Res) - "Buprenorphine may have a small benefit for depressive symptoms. Future research should clarify the dose response relationship between buprenorphine and depression."

Journal • Retrospective data • Review • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry • Suicidal Ideation

Opioid Derivatives as Antidepressants (ACNP 2022) - "Additionally, uncontrolled clinical studies have described the efficacy of low-dosage treatment with opioids, including buprenorphine, for treatment-refractory depression, and recent studies have indicated that mu-opioid receptor agonism may play a key role in the antidepressant properties of tianeptine. The opioid modulator buprenorphine/samidorphan is a combination of a mu-opioid receptor agonist with kappa-opioid receptor antagonism (buprenorphine) and of a mu-opioid receptor antagonist (samidorphan)...The antidepressant potential of this functional kappa-opioid antagonist has been supported by the observation of antidepressant activity in a pilot study of a specific kappa-opioid receptor antagonist. There is therefore significant interest in the development of kappa-opioid receptor antagonists as treatments for depression."

CNS Disorders • Depression • Mood Disorders • Psychiatry

Evaluating the Efficacy of Opioid Receptor Antagonists as an Adjunct for Bipolar Disorder: A Systematic Review (APA 2022) - "The search strategy contained terms for centrally acting ORAs including nalmefene, naloxone, naltrexone, and samidorphan; buprenorphine was also included based on a previous meta-analysis. This review found no strong evidence that supports the efficacy of ORAs as an adjunct in BP at currently used doses. Some considerations when evaluating the findings of this review is that this search does not to capture earlier studies or assess the effects of distinct mechanisms and affinities of available ORAs. Despite this, there is paucity of literature in this clinical domain and further research is warranted."

Clinical • Review • Addiction (Opioid and Alcohol) • Bipolar Disorder • CNS Disorders • Mood Disorders • Pain • Psychiatry

Alkermes Beats Investor Suit Over FDA Drug Application Process (Bloomberg Law) - "Complaint mischaracterizes FDA dealings, judge says. Suit challenges stock drop after drug denied approval....Alkermes PLC defeated a securities lawsuit claiming it misled investors about its efforts to get FDA approval for a new depression drug, when a federal judge in New York said the investors’ characterization of the company’s dealings with the Food and Drug Administration 'borders on pure fantasy.'"

Corporate lawsuit • CNS Disorders • Depression

Keeping up with the clinical advances: depression. (PubMed, CNS Spectr) - "Pharmaceuticals that target the glutamatergic system include ketamine, esketamine, and rapastinel; brexanolone and SAGE-217 target the GABAergic system; minocycline targets the inflammatory system; and the combinatory agent buprenorphine + samidorphan targets the opioidergic system...Novel therapeutics have the potential to improve both patient mood symptomatology and economical productivity, reducing the debased human capital costs associated with MDD. Furthermore, a selection of therapeutic targets provides diverse treatment options which may be beneficial to the patient considering the heterogeneity of MDD."

Clinical • Journal • CNS Disorders • Depression • Immunology • Mood Disorders

Results from a long-term open-label extension study of adjunctive buprenorphine/samidorphan combination in patients with major depressive disorder. (PubMed, Neuropsychopharmacology) - "BUP/SAM was generally well tolerated, with a low risk of abuse and an AE profile consistent with those seen in placebo-controlled studies. Withdrawal reports were uncommon and of limited clinical impact."

Clinical • Journal • CNS Disorders • Constipation • Depression • Gastrointestinal Disorder • Mood Disorders • Suicidal Ideation

Abuse Potential of Buprenorphine/Samidorphan Combination Compared to Buprenorphine and Placebo: A Phase 1 Randomized Controlled Trial. (PubMed, J Clin Pharmacol) - P1 | "Fewer participants reported adverse events associated with abuse potential with BUP/SAM than with buprenorphine alone, and the overall safety profile of BUP/SAM was consistent with prior reports in healthy volunteers. These findings indicate that samidorphan substantially reduces the abuse potential of buprenorphine in the BUP/SAM combination."

Clinical • Journal • P1 data • Addiction (Opioid and Alcohol) • CNS Disorders • Depression • Mood Disorders

Targeting opioid dysregulation in depression for the development of novel therapeutics. (PubMed, Pharmacol Ther) - "Finally, putative opioid based antidepressants that are being tested in clinical trials, ALKS5461, JNJ-67953964 (formerly LY2456302 and CERC-501) and BTRX-246040 (formerly LY-2940094) will be discussed. This review will illustrate the potential therapeutic value of targeting opioid dysregulation in developing novel therapies for major depression disorder."

Journal • CNS Disorders • Depression • Mood Disorders

A meta-analysis of the potential antidepressant effects of buprenorphine versus placebo as an adjunctive pharmacotherapy for treatment-resistant depression. (PubMed, J Affect Disord) - "This meta-analysis did not reveal a significant reduction in depression symptom severity in individuals with TRD after an adjunctive intervention with buprenorphine when compared to placebo. However, more optimal doses of buprenorphine (2 mg/day) and longer treatment lengths should be explored."

Journal • Retrospective data • Review • CNS Disorders • Depression • Mood Disorders

Intra-Cellular down 7% premarket on FDA rejection of Alkermes' application for MDD med ALKS 5461 (SeekingAlpha) - "Intra-Cellular Therapies...slips 7% premarket in sympathy with Alkermes' 18% plunge after receiving a Refusal to File letter in response to its ALKS 5461 application. Investors apparently perceive heightened risk for schizophrenia and MDD candidate lumateperone. Its U.S. filing for the former should be completed by mid-year."

NDA • Stock price • CNS Disorders • Depression • Schizophrenia

A Long Term Study of ALKS 5461 in the Treatment of Refractory Major Depressive Disorder (MDD) (clinicaltrials.gov) - P3b; N=175; Terminated; Sponsor: Alkermes, Inc.; N=250 ➔ 175; Trial completion date: Jul 2021 ➔ May 2020; Enrolling by invitation ➔ Terminated; Trial primary completion date: Jul 2021 ➔ May 2020; Sponsor Decision

Enrollment change • Trial completion date • Trial primary completion date • Trial termination • CNS Disorders • Depression • Mood Disorders

Alkermes to present clinical and real-world data at upcoming 30th Annual Psych Congress (Businesswire) - "Alkermes...today announced the presentation of 11 posters highlighting clinical and real-world data pertaining to the company’s schizophrenia, opioid dependence and depression portfolios at the upcoming 30th Annual Psych Congress (Psych Congress) in New Orleans, Sept. 16-19, 2017....Poster #124: 'ALKS 5461: A Buprenorphine-Samidorphan Combination for Major Depression,” on Sunday, Sept. 17, 2017, 1:30 – 2:30 p.m. CT' "

Clinical data • CNS Disorders • Depression

"$AGN shares have been sliding all day, look to close off nearly 10%; don't blame 3Q earnings: @Allergan set to face hostile #FDA reviewers at Thursday's joint mtg of #PDAC and #DSaRM adcoms reviewing MDD therapy ALKS-5461" (@BioWorld)

Alkermes submits New Drug Application to U.S. FDA for ALKS 5461 for the adjunctive treatment of major depressive disorder (PRNewswire) - "Alkermes...today announced that it has submitted a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for ALKS 5461, a once-daily, oral investigational medicine with a novel mechanism of action for the adjunctive treatment of major depressive disorder (MDD). The NDA submission is based on a comprehensive clinical efficacy and safety package with data from more than 30 clinical trials and more than 1,500 patients with MDD."

NDA • CNS Disorders • Depression

Alkermes plc reports financial results for the year ended Dec. 31, 2017 and provides financial expectations for 2018 (PRNewswire) - "2018 Expected Milestones: Assignment of PDUFA target action date, following NDA acceptance (Q2); Potential Advisory Committee meeting and FDA action (H2)."

FDA event • PDUFA date • CNS Disorders • Depression

A Study of the Abuse Liability Potential of ALKS 5461 in Healthy, Non-Dependent, Recreational Opioid Users (clinicaltrials.gov) - P1; N=56; Completed; Sponsor: Alkermes, Inc.; Recruiting ➔ Completed

Trial completion • Biosimilar

Opioid Modulation With Buprenorphine/Samidorphan as Adjunctive Treatment for Inadequate Response to Antidepressants: A Randomized Double-Blind Placebo-Controlled Trial. (PubMed) - Am J Psychiatry - "The buprenorphine/samidorphan combination is a novel and promising candidate for treatment of major depressive disorder in patients who have an inadequate response to standard antidepressants."

Journal • Biosimilar • Depression

Alkermes: Jefferies London Healthcare Conference (Alkermes) - "FORWARD-1 Results: MADRS Reduction From Baseline Continued Through Week 8"

P3 data • Depression

ALKS 5461: Launch in US for MDD in 2019 (Alkermes) - Corporate Presentation

Launch US • CNS Disorders • Depression • Mood Disorders • Psychiatry

Alkermes announces topline results of FORWARD-3 and FORWARD-4, two phase 3 studies of ALKS 5461 in major depressive disorder (Businesswire) - P3, N=429, 385; FORWARD-3 (NCT02158546), FORWARD-4 (NCT02158533); Sponsor: Alkermes; "Neither study met primary endpoint; additional analyses of FORWARD-4 provide supportive evidence of efficacy...Third efficacy study, FORWARD-5, will recruit additional patients; Data may provide regulatory path forward for ALKS 5461."

Anticipated P3 data • Enrollment change • P3 data: top line • Depression

Alkermes: Q4 2015 Results Earnings Call (Alkermes) - Anticipated presentation of data from P3 FORWARD-4 trial (NCT02158533) in major depressive disorder at ASCP (May 30-Jun 3, 2016)

Anticipated P3 data • Depression

Alkermes reports on outcome of FDA Advisory Committee Meeting on ALKS 5461 for the adjunctive treatment of major depressive disorder (PRNewswire) - "Alkermes plc...today announced that the Psychopharmacologic Drugs Advisory Committee and the Drug Safety and Risk Management Advisory Committee, appointed by the U.S. Food and Drug Administration (FDA), met to review the company's New Drug Application (NDA) for ALKS 5461. The committee jointly voted that the benefit-risk profile was not adequate to support approval (Vote: 2 Yes/ 21 No)."

FDA event • CNS Disorders • Depression • Mood Disorders • Psychiatry

Alkermes announces achievement of milestones for CNS medicines in proprietary product and pipeline portfolio (Businesswire) - P3, N=66; FORWARD (NCT02085135); Sponsor: Alkermes; "Alkermes also announced positive topline results from a recently-completed human abuse potential study of ALKS 5461, a once-daily, oral investigational medicine with a novel mechanism of action for the adjunctive treatment of major depressive disorder."

P3 data: top line • Depression

ALKS-5461: Anticipated expiry of patents in US in 2021, 2025, 2030, 2031, 2032 (Alkermes) - Annual Report 2016

Anticipated patent expiry • CNS Disorders • Depression

ALKS 5461: Patent protection in US related to method of treatment until 2030 (Alkermes) - Corporate Presentation: Patent protection in US related to formulation until 2032; Patent protection in US related to composition of matter until 2031

Patent • CNS Disorders • Depression • Mood Disorders • Psychiatry