Axxonis Pharma AG is a Swiss biotechnology company focused on the development of novel therapies for neurodegenerative and psychiatric disorders[@axxonis2024]. The company is known for its pioneering work on MAO-B inhibitors and other neurological drug candidates, with a particular emphasis on Parkinson's disease therapeutics.
Founded in 2005 in Switzerland, Axxonis built a reputation for innovative approaches to modulating monoamine oxidase pathways and developed one of the few MAO-B inhibitors to reach FDA approval. The company's research focused on creating reversible, selective MAO-B inhibitors with improved safety profiles compared to older, irreversible inhibitors.
Mechanism: Reversible MAO-B (Monoamine Oxidase B) inhibitor
Development Stage: FDA/EMA Approved
Description: Safinamide is a novel, reversible MAO-B inhibitor developed by Axxonis for the treatment of Parkinson's disease. It was designed to provide both dopaminergic and non-dopaminergic benefits through selective and reversible MAO-B inhibition[@fda2017].
Pharmacological Properties
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Overview
Axxonis Pharma AG is a Swiss biotechnology company focused on the development of novel therapies for neurodegenerative and psychiatric disorders[@axxonis2024]. The company is known for its pioneering work on MAO-B inhibitors and other neurological drug candidates, with a particular emphasis on Parkinson's disease therapeutics.
Founded in 2005 in Switzerland, Axxonis built a reputation for innovative approaches to modulating monoamine oxidase pathways and developed one of the few MAO-B inhibitors to reach FDA approval. The company's research focused on creating reversible, selective MAO-B inhibitors with improved safety profiles compared to older, irreversible inhibitors.
Mechanism: Reversible MAO-B (Monoamine Oxidase B) inhibitor
Development Stage: FDA/EMA Approved
Description: Safinamide is a novel, reversible MAO-B inhibitor developed by Axxonis for the treatment of Parkinson's disease. It was designed to provide both dopaminergic and non-dopaminergic benefits through selective and reversible MAO-B inhibition[@fda2017].
Pharmacological Properties
Reversible inhibition: Unlike irreversible MAO-B inhibitors (selegiline, rasagiline), safinamide binds reversibly to the enzyme, allowing for more flexible dosing and reduced risk of drug interactions
Selectivity: High selectivity for MAO-B over MAO-A, minimizing the risk of tyramine-induced hypertensive crisis (cheese effect)
Additional mechanisms: Modulates glutamate release and sodium channel blockade may contribute to neuroprotective effects
Clinical Benefits
Dopaminergic effects: Reduces dopamine metabolism, increasing dopamine availability in the striatum
Non-dopaminergic effects: Glutamate modulation through MAO-B inhibition may provide neuroprotection
Motor symptoms: Improves motor function, reduces "off" time, and increases "on" time without troublesome dyskinesia
Safety profile: Reduced risk of tyramine-induced hypertensive crisis compared to irreversible inhibitors
Clinical Development
Phase I: Established safety and pharmacokinetics in healthy volunteers
Phase II: Demonstrated efficacy in improving motor symptoms
Phase III: CONFIDENT and SETTLE trials showed significant improvements in motor function and daily "on" time
Approvals:
EMA approval (2015) — marketed as Azilect
FDA approval (2017) — marketed as Xadago
Additional Programs
While safinamide was the flagship program, Axxonis explored additional neurological candidates:
Second-generation MAO-B inhibitors: Follow-on compounds with improved pharmacokinetics
Combination therapies: Approaches combining MAO-B inhibition with other mechanisms
Neuroprotective strategies: Small molecules targeting oxidative stress and mitochondrial dysfunction
Acquisition by Novartis
In 2017, Novartis acquired Axxonis Pharma AG, gaining full rights to safinamide and the company's MAO-B inhibitor platform[@novartis2017]. The acquisition reflected the pharmaceutical industry's recognition of:
The growing Parkinson's disease market
The value of reversible MAO-B inhibition
Axxonis's expertise in CNS drug development
Safinamide continues to be marketed globally under the Novartis portfolio as an important treatment option for Parkinson's disease patients.
Scientific Rationale
Monoamine Oxidase B in Parkinson's Disease
MAO-B is an enzyme that metabolizes dopamine in the brain. In Parkinson's disease, dopamine-producing neurons are lost, leading to motor symptoms. MAO-B inhibitors:
Increase dopamine levels: By reducing enzymatic breakdown
Reduce oxidative stress: MAO-B activity produces hydrogen peroxide as a byproduct
May slow disease progression: Neuroprotective effects observed in preclinical models