H. Lundbeck A/S (Lundbeck) announces data from the TALISMAN natural history study, as well as additional data from the AMULET trial of amlenetug (Lu AF82422) in Multiple System Atrophy (MSA) at the International Congress of Parkinson's Disease and Movement disorders (MDS congress) in Philadelphia, USA.

The TALISMAN study is a step forward in Lundbeck's commitment to understanding the course of MSA and developing innovative therapies that address significant unmet needs in this devastating and rapidly progressive disease.

The TALISMAN study was a prospective, observational, multicenter cohort study, which explored disease progression in a cohort of relatively early stage MSA patients in China. The TALISMAN study helps to better understand the epidemiology of the early stages of the disease in a relatively long observation time in the Chinese population. These natural history data are used to inform Lundbeck's MSA development program with amlenetug (Lu AF82422).

The AMULET trial was a phase II, double-blind, randomized trial of amlenetug (Lu AF82422) in MSA. The headline results of the AMULET trial were presented at the International Conference on Alzheimer's and Parkinson's Diseases and related neurological disorders (AD/PD 2024) in March 2024. Subgroup analyses will be presented.

Based on the encouraging AMULET trial outcomes, Lundbeck is on track to initiate a phase III trial at the beginning of 2025.

"I have been very impressed with Lundbeck's dedication not only to advance therapeutic strategies but also trial infrastructure and outcome assessments for MSA. The team truly embraces input from the scientific community which I believe is a key factor for the encouraging results of the AMULET trial and the general success of their MSA program," said Wolfgang Singer, associate professor of neurology at Mayo Clinic Rochester.

Scientific presentation from Lundbeck at MDS congress

• TALISMAN was a prospective, multicenter, observational study conducted in 8 sites across China.
• A total of 89 participants were enrolled; of these about half (52%) had MSA-C and 48% participants had MSA-P.
• The mean ± SE [95%CI] rate of Total UMSARS progression was 1.27 ± 0.13 [1.01, 1.53] points per month.
• Participants showed a progression of 0.64 ± 0.06 [0.51, 0.76] points/month on UMSARS Part I and 0.62 ± 0.07 [0.47, 0.77] points/month on UMSARS Part II

• AMULET (NCT05104476) was a double-blind, placebo-controlled trial investigating the safety and efficacy of monthly IV infusions with Lu AF82422 in patients with MSA. 
• 61 participants were treated with Lu AF82422 (n=40) or placebo (n=21).
• The primary endpoint showed a non-statistically significant 19% slowing of clinical progression measured by UMSARS TS in the Lu AF82422 group vs placebo. 
• The slope analysis of mUMSARS, UMSARS part I and part II showed a consistent slowing in clinical progression of 27%, 22% and 17%, respectively. 
• Post-hoc analysis of a less impaired subgroup showed 42% slowing of progression in Lu AF82422 treated patients.
• A trend towards smaller regional MRI volumetric reduction in the Lu AF82422 group vs placebo was also observed. 
• Lu AF82422 was generally well tolerated.

About the TALISMAN study
TALISMAN study was a prospective, multicenter, observational study conducted in 8 sites across China. Eligible participants were aged 40-75 years, with possible or probable MSA of the parkinsonian (MSA-P) or cerebellar (MSA-C) subtype, anticipated survival of at least 3 years, UMSARS-Chinese version Part I score of ≤16 (omitting Q11 on sexual function), and a Montreal Cognitive Assessment score ≥22. Patients were followed for one year; standard of care treatments were prescribed according to routine clinical practice. Disease progression was analyzed using a linear mixed model of Total UMSARS (Part I+II) progression, including baseline, Month 6 and Month 12 data.

About the AMULET trial
AMULET trial was a phase II, randomized, double-blind, placebo-controlled clinical trial of Lu AF82422 as a potential treatment for patients with MSA. A total of N=61 MSA patients were randomized 2:1 to either Lu AF82422 or placebo and treated between 48 to 72 weeks, followed by an ongoing 96 weeks open-label extension period offering all participants to receive treatment with Lu AF82422.

The primary objective was to evaluate the efficacy of Lu AF82422 on clinical progression in patients with MSA, aiming at showing a slowing in clinical progression in the active treatment arm compared to placebo on a 5% significance level evaluated 1-sided as well as safety and tolerability. The secondary objectives included evaluation of Lu AF82422 on patient's functioning, disease severity and other aspects of MSA.
Lu AF82422 was delivered as an intravenous infusion every four weeks.

About amlenetug (Lu AF82422)
Amlenetug Lu AF82422 is a human monoclonal antibody (mAb) that recognizes and binds to all major forms of extracellular α-syn and thereby is believed to prevent uptake and inhibit seeding of aggregation. Amlenetug (Lu AF82422) has an active Fc region, which may increase immune-mediated clearance of α-syn/mAb complexes through microglia mediated uptake. Amlenetug (Lu AF82422) is being developed by Lundbeck under a joint research and licensing agreement between Lundbeck and Genmab A/S. 

About Multiple System Atrophy
MSA is a rapidly progressing rare condition of the nervous system that causes damage to nerve cells in the brain. MSA is seriously debilitating and places a high disease burden on patients. Symptoms of MSA usually start between 55 and 60 years of age and the patients typically live for 6 to 9 years after symptom onset1.

In a person with MSA, an abnormal build-up of the protein alpha-synuclein is thought to be responsible for damaging areas of the brain that control balance, movement, and the body's normal functions1. The symptoms of MSA are wide-ranging and include muscle control problems, similar to those of Parkinson's disease1. Many different functions of the body can be affected, and symptoms including urinary incontinence, frequent falling, and unintelligible speech occur within 3 years of disease onset and are accompanied by reduced capacity to live independently. Death is often due to respiratory problems. Although there are many different possible symptoms of MSA, not everyone who is affected will experience all of them. There is currently no cure for MSA and no available treatment to slow its progression[1].

References:

1 - NHS: Multiple system atrophy - NHS (www.nhs.uk)
H. Lundbeck A/S (Lundbeck)

MSA-P: Multiple System Atrophy - parkinsonian type MSA-C: Multiple System Atrophy - Cerebellar type, UMSARS: Unified Multiple System Atrophy Rating Scale, TS: Total Score
 

Contacts

Thomas Mikkel Mortensen Palle Holm Olesen
Media Relations Lead, Corp. Communication Vice President, Investor Relations
THMR@lundbeck.com PALO@lundbeck.com
+45 30 83 30 24 +45 30 83 24 26

About H. Lundbeck A/S
Lundbeck is a biopharmaceutical company focusing exclusively on brain health. With more than 70 years of experience in neuroscience, we are committed to improving the lives of people with neurological and psychiatric diseases.

Brain disorders affect a large part of the world's population, and the effects are felt throughout society. With the rapidly improving understanding of the biology of the brain, we hold ourselves accountable for advancing brain health by curiously exploring new opportunities for treatments.

As a focused innovator, we strive for our research and development programs to tackle some of the most complex neurological challenges. We develop transformative medicines targeting people for whom there are few or no treatments available, expanding into neuro-specialty and neuro-rare from our strong legacy within psychiatry and neurology.

We are committed to fighting stigma and we act to improve health equity. We strive to create long term value for our shareholders by making a positive contribution to patients, their families and society as a whole.

Lundbeck has approximately 5,500 employees in more than 50 countries and our products are available in more than 80 countries. For additional information, we encourage you to visit our corporate site www.lundbeck.com (https://www.lundbeck.com/global) and connect with us via LinkedIn (https://www.linkedin.com/company/lundbeck/).