FDA Grants Fast Track Designation to Amlenetug for Possible Treatment of Multiple System Atrophy

Author(s):

Luke Halpern, Assistant Editor

Key Takeaways

Amlenetug received FDA fast track designation for MSA treatment, showing promise despite not meeting primary endpoints in phase 2 trials.
The AMULET trial indicated a 19% slowing in MSA progression and smaller MRI volumetric reduction with amlenetug treatment.
Amlenetug was well-tolerated, leading to the initiation of the phase 3 MASCOT trial to further evaluate its efficacy and safety.
MSA is a rapidly progressing neurological disorder with no cure, underscoring the potential significance of amlenetug's development.

Amlenetug could provide a treatment option for patients with multiple system atrophy, a progressive and rare condition that causes damage to the brain’s nerve cells.

The FDA granted fast track designation (FTD) to amlenetug, an investigational human monoclonal antibody from Lundbeck, for further examination as a potential novel therapy for patients with multiple system atrophy (MSA), according to a news release from Lundbeck. Amlenetug is designed to bind to major forms of extracellular α-synuclein, which prevents uptake and inhibits seeding of aggregation.¹

Parkinson and alzheimer female senior elderly patient hand with physician doctor exam in hospice care room.

Multiple system atrophy can cause myriad muscle control complications, such as difficulty walking or eating. | Image Credit: © Khunatorn - stock.adobe.com

The new designation is based on positive data from the phase 2 AMULET clinical trial (NCT03611569), recently presented at the International Conference on Alzheimer’s and Parkinson’s Diseases and related neurological disorders (AD/PD) in Lisbon, Portugal. Although amlenetug did not meet its primary end point in the trial, it showed important slowing of MSA progression, allowing for the issuing of FDA FTD.^1,2

The data indicated that amlenetug, also known as Lu AF82422, showed a non-statistically significant slowing of clinical progression (19%) as measured by both parts of the Unified Multiple System Atrophy Rating Scale (UMSARS) total score versus placebo. However, according to the slope analysis of UMSARS, scores in part 1 and part 2 demonstrated a consistent slowing in the clinical progression of MSA in patients treated with amlenetug.³

Additionally, there was a trend towards smaller regional MRI volumetric reduction in patients treated with amlenetug compared with those treated with placebo. In a major development, amlenetug was generally well-tolerated among patients treated. Based on these positive results, Lundbeck recently initiated MASCOT (NCT06706622), a phase 3, interventional, randomized, double-blind, parallel-group, placebo-controlled, optional open-label extension trial conducted globally.^1,3,4

The trial, which comprises 2 parts, aims to evaluate the efficacy, safety, and tolerability of amlenetug in patients with MSA. In the first part, a double-blind period, participants are randomized to receive either high or low doses of amlenetug or placebo for 72 weeks. In the second part, an open-label extension period, all enrolled participants will be offered treatment with amlenetug. Investigators plan to deliver amlenetug as an intravenous (IV) infusion every 4 weeks.¹

"We are pleased that amlenetug has received fast track designation for the potential treatment of multiple system atrophy,” Johan Luthman, executive vice president and head of research and development at Lundbeck, said in the news release. “This is a step forward in our commitment to address significant unmet needs in this devastating disease."¹

Results from phase 1 of AMULET, which was a first-in-human study, indicated that single IV infusions of the amlenetug were safe and well-tolerated, with no serious adverse events observed over the course of the trial. Furthermore, the results indicated engagement with the peripheral target of plasma concentration. The investigators of that study deemed the safety and pharmacokinetic profile of amlenetug “appropriate for further clinical development.”⁵

MSA, a rapidly progressing condition of the nervous system, causes damage to nerve cells located in the brain. It places a major burden on patients affected, with wide-ranging symptoms including muscle control problems leading to frequent falling, urinary incontinence, and unintelligible speech, which could occur within 3 years of disease onset. Because there is currently no cure for MSA, the possible future approval of amlenetug would fill a major need for patients.¹

REFERENCES

1. H Lundbeck A/S. Lundbeck’s potential treatment amlenetug for multiple system atrophy receives Fast Track Designation from the FDA. PR Newswire. News Release. Released February 12, 2025. Accessed February 13, 2025. https://www.prnewswire.com/news-releases/lundbecks-potential-treatment-amlenetug-for-multiple-system-atrophy-receives-fast-track-designation-from-the-fda-302374577.html

2. ClinicalTrials.gov. Lu AF82422 in healthy non-Japanese and Japanese subjects and in patients with Parkinson’s disease. National Library of Medicine. Last Updated September 12, 2021. Accessed February 13, 2025. https://clinicaltrials.gov/study/NCT03611569

3. H Lundbeck A/S. Lundbeck presents encouraging results from the Lu AF82422 trial for multiple system atrophy at the international AD/PD 2024 conference on neurodegenerative disorders. News Release. Released March 5, 2024. Accessed February 13, 2025. https://mb.cision.com/Main/18215/3940069/2643599.pdf

4. ClinicalTrials.gov. A trial of Lu AF82422 in participants with multiple system atrophy (MSA) (MASCOT). National Library of Medicine. Last Updated January 9, 2025. Accessed February 13, 2025. https://clinicaltrials.gov/study/NCT06706622?term=NCT06706622&rank=1

5. Burr L, Wiedemann J, Larsen F, et al. Randomized phase 1 trial of the α-synuclein antibody Lu AF82422. Movement Disorders. 2024;39(6):936-944. doi:10.1002/mds.29784