amlenetug (Lu AF82422) / Lundbeck, Genmab - LARVOL DELTA

Lundbeck's potential treatment for Multiple System Atrophy granted Orphan Drug Designation in Japan (PRNewswire) - "The Ministry of Health, Labor, and Welfare (MHLW) in Japan has granted Orphan Drug Designation (ODD) to Lundbeck's investigational drug, amlenetug, a potential new treatment option targeting Multiple System Atrophy (MSA)."

Orphan drug • Multiple System Atrophy

Lundbeck’s potential treatment amlenetug for Multiple System Atrophy receives Fast Track Designation from the FDA (PRNewswire) - "H. Lundbeck A/S (Lundbeck) today announced that amlenetug has received Fast Track designation from the United States (US) Food and Drug Administration (FDA)....This designation is based on the outcome of AMULET..."

Fast track • Multiple System Atrophy

An update on immune-based alpha-synuclein trials in Parkinson's disease. (PubMed, J Neurol) - "Specifically, UB-312, AFFITOPE PD01A, PD03A and ACI-7104.056 are designed to provoke an immune response against α-syn (active immunisation), while Prasinezumab and Cinpanemab, MEDI1341 and Lu AF82422 focus on directly targeting α-syn aggregates (passive immunisation). Despite some promising results, challenges such as variable efficacy and trial discontinuations persist. Future research must address these challenges to advance disease-modifying therapies for PD around this therapeutic target."

Journal • Review • CNS Disorders • Movement Disorders • Parkinson's Disease

MASCOT: A Trial of Lu AF82422 in Participants With Multiple System Atrophy (MSA) (clinicaltrials.gov) - P3 | N=360 | Recruiting | Sponsor: H. Lundbeck A/S | Not yet recruiting ➔ Recruiting

Enrollment open • CNS Disorders • Movement Disorders • Multiple System Atrophy

MASCOT: A Trial of Lu AF82422 in Participants With Multiple System Atrophy (MSA) (clinicaltrials.gov) - P3 | N=360 | Not yet recruiting | Sponsor: H. Lundbeck A/S

New P3 trial • CNS Disorders • Movement Disorders • Multiple System Atrophy

Lundbeck initiates a phase III trial with amlenetug for the treatment of Multiple System Atrophy (Lundbeck Press Release) - "H. Lundbeck A/S (Lundbeck) today announced the advancement of the clinical development of amlenetug (Lu AF82422) for the treatment of MSA with the initiation of MASCOT, a randomized, double-blind, phase III trial."

Trial status • CNS Disorders • Multiple System Atrophy

A Trial Investigating Lu AF82422 in Healthy Chinese and Caucasian Adults (clinicaltrials.gov) - P1 | N=24 | Completed | Sponsor: H. Lundbeck A/S | Active, not recruiting ➔ Completed

Trial completion

Safety and Efficacy of the Anti-alpha Synuclein Monoclonal Antibody Lu AF82422 for the Treatment of Patients with MSA: Results from the Phase 2 AMULET Trial (MDS Congress 2024) - P2 | "Although the trial did not meet its primary endpoint in the overall population, a potential for Lu AF82422 to slow MSA clinical progression was shown. The signal of efficacy was more pronounced in a less impaired population when a treatment with an a-syn antibody would be expected to be most beneficial. These data support the further investigation of Lu AF82422 in a phase 3 trial designed to confirm its potential effects on clinical progression in MSA."

Clinical • P2 data • CNS Disorders • Multiple System Atrophy • Parkinson's Disease

AMULET: A Study of Lu AF82422 in Participants With Multiple System Atrophy (clinicaltrials.gov) - P2 | N=64 | Active, not recruiting | Sponsor: H. Lundbeck A/S | Trial completion date: Feb 2025 ➔ May 2026

Trial completion date • CNS Disorders • Movement Disorders • Multiple System Atrophy

A Trial Investigating Lu AF82422 in Healthy Chinese and Caucasian Adults (clinicaltrials.gov) - P1 | N=24 | Active, not recruiting | Sponsor: H. Lundbeck A/S | Recruiting ➔ Active, not recruiting

Enrollment closed

A Trial Investigating Lu AF82422 in Healthy Chinese and Caucasian Adults (clinicaltrials.gov) - P1 | N=24 | Recruiting | Sponsor: H. Lundbeck A/S | Not yet recruiting ➔ Recruiting

Enrollment open

Randomized Phase I Trial of the α-Synuclein Antibody Lu AF82422. (PubMed, Mov Disord) - P1 | "The safety and pharmacokinetic profile of Lu AF82422 were appropriate for further clinical development, and results indicated peripheral target engagement. The central target engagement observed in participants with PD indicates that the doses of Lu AF82422 tested may provide CSF concentrations sufficient to target aggregated forms of α-syn."

Journal • P1 data • CNS Disorders • Infectious Disease • Movement Disorders • Pain • Parkinson's Disease

SUPPORTIVE RESULTS FROM THE AMULET PHASE 2, DOUBLE-BLIND, RANDOMIZED EXPLORATORY TRIAL OF LU AF82422 IN MULTIPLE SYSTEM ATROPHY (ADPD 2024) - No abstract available

Clinical • P2 data • CNS Disorders • Movement Disorders • Multiple System Atrophy

A Trial Investigating Lu AF82422 in Healthy Chinese and Caucasian Adults (clinicaltrials.gov) - P1 | N=24 | Not yet recruiting | Sponsor: H. Lundbeck A/S

New P1 trial

AMULET: A Study of Lu AF82422 in Participants With Multiple System Atrophy (clinicaltrials.gov) - P2 | N=64 | Active, not recruiting | Sponsor: H. Lundbeck A/S | Trial completion date: Mar 2024 ➔ Feb 2025

Trial completion date • CNS Disorders • Movement Disorders • Multiple System Atrophy

Baseline characteristics for patients with multiple system atrophy entering a randomized, controlled study of the anti-α-synuclein monoclonal antibody Lu AF82422 (MDS Congress 2023) - P2 | "Study randomization is complete and baseline characteristics are consistent with a population of patients with MSA who are still relatively early in their disease course, and who might be good candidates to assess the slowing of clinical progression with a therapy preventing α-syn accumulation."

Clinical • CNS Disorders • Multiple System Atrophy • Parkinson's Disease

AMULET: A Study of Lu AF82422 in Participants With Multiple System Atrophy (clinicaltrials.gov) - P2 | N=64 | Active, not recruiting | Sponsor: H. Lundbeck A/S | Trial completion date: Mar 2025 ➔ Mar 2024

Trial completion date • CNS Disorders • Movement Disorders • Multiple System Atrophy • NEFL

AMULET: A Study of Lu AF82422 in Participants With Multiple System Atrophy (clinicaltrials.gov) - P2 | N=64 | Active, not recruiting | Sponsor: H. Lundbeck A/S | Trial completion date: Aug 2023 ➔ Mar 2025 | Trial primary completion date: May 2023 ➔ Nov 2023

Trial completion date • Trial primary completion date • CNS Disorders • Movement Disorders • Multiple System Atrophy • NEFL

AMULET: A Study of Lu AF82422 in Participants With Multiple System Atrophy (clinicaltrials.gov) - P2 | N=60 | Active, not recruiting | Sponsor: H. Lundbeck A/S | Recruiting ➔ Active, not recruiting

Enrollment closed • CNS Disorders • Movement Disorders • Multiple System Atrophy • NEFL

The anti-alpha-synuclein antibody Lu AF82422 binds to pathological alpha-synuclein species from human brains and inhibits seeded alpha-synuclein aggregation (MDS Congress 2022) - "Lu AF82422 binds to aSyn aggregates isolated from disease-brain material with high affinity and dose-dependently inhibits seeding of aSyn aggregates in vitro and in vivo. Based on the strong preclinical findings, Lu AF82422 has been progressed into clinical development as a potential disease-modifying treatment for synucleinopathies."

Alzheimer's Disease • CNS Disorders • Dementia • Lewy Body Disease • Multiple System Atrophy • Parkinson's Disease

The anti-alpha-synuclein antibody Lu AF82422 was safe and well tolerated in a FIH-SAD study in healthy subjects and patients with PD (MDS Congress 2022) - "In this first-in-human (FIH) SAD study, Lu AF82422 was safe and well tolerated in HS and PD patients. PK and plasma TE were as expected. Data from the FIH SAD study combined with in vitro binding of Lu AF82422 to monomer and aggregated aSyn indicate that the doses of Lu AF82422 tested may provide CSF concentrations sufficient to target aggregated forms of aSyn."

Clinical • Alzheimer's Disease • CNS Disorders • Dementia • Lewy Body Disease • Multiple System Atrophy • Parkinson's Disease

AMULET: A Study of Lu AF82422 in Participants With Multiple System Atrophy (clinicaltrials.gov) - P2; N=60; Recruiting; Sponsor: H. Lundbeck A/S; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open • CNS Disorders • Movement Disorders • Multiple System Atrophy • MRI

Lundbeck launches a phase II study for potential new treatment of multiple system atrophy (Market Screener) - “H. Lundbeck A/S (Lundbeck), announces that it has expanded its clinical-stage pipeline and is ready to initiate the AMULET study, which is designed to confirm the potential of Lu AF82422 as a treatment to slow the rate of disease progression of multiple system atrophy (MSA)….Earlier this year, Lu AF82422 was granted orphan drug designation by the European Medicines Agency (EMA), and the AMULET study has now been approved by the FDA and is ready to enroll the first patient….Lu AF82422 has been demonstrated to be well-tolerated in a completed phase I single ascending dose study. The safety of Lu AF82422 will continue to be monitored in the AMULET study.”

New P2 trial • CNS Disorders • Multiple System Atrophy

AMULET: A Study of Lu AF82422 in Participants With Multiple System Atrophy (clinicaltrials.gov) - P2; N=60; Not yet recruiting; Sponsor: H. Lundbeck A/S

Clinical • New P2 trial • CNS Disorders • Movement Disorders • Multiple System Atrophy • MRI

Nonclinical safety evaluation, pharmacokinetics, and target engagement of Lu AF82422, a monoclonal IgG1 antibody against alpha-synuclein in development for treatment of synucleinopathies. (PubMed, MAbs) - "Target engagement was shown in plasma and cerebrospinal fluid. Taken together, the nonclinical data indicated no safety signal of concern and provided adequate safety margins between observed safe doses in animals and the planned dose levels in the FIH SAD study."

Clinical • Journal • PK/PD data • CNS Disorders • Movement Disorders • Multiple System Atrophy • Parkinson's Disease