Qilu Pharmaceutical's Rasagiline Mesylate Tablets (First Generic in China) Nears Approval for Parkinson’s Disease Treatment

By Cai Cai

Recently, the marketing application (Acceptance No.: CYHS1900695) for Qilu Pharmaceutical’s rasagiline mesylate tablets, filed as a Class 4 generic drug, has been updated to “under review,” with approval expected in the near future. As the submission was made under the new Class 4 generic drug pathway, it will be deemed to have passed the consistency evaluation upon approval.

(Source: NMPA)

Rasagiline Mesylate Tablets (Brand Name: Azilect), co-developed by Lundbeck A/S of Denmark and Teva, are a therapeutic agent for Parkinson’s disease (PD). As a second-generation monoamine oxidase-B (MAO-B) inhibitor, it exerts potent, highly selective, and irreversible inhibition of type B monoamine oxidase.

Parkinson’s disease (PD) is the second most common neurodegenerative disorder, with approximately 6 million patients worldwide, over 50% of whom are in China. The prevalence of PD among individuals aged 65 years and older in China is 1.7%, corresponding to an estimated 2.7 million patients, yet the treatment rate stands at only 20%. With the aging population, the global number of PD patients is projected to reach 9 million by 2030, with China’s patient population expected to reach 5 million.

In healthy individuals, dopamine is primarily metabolized by two enzymes: monoamine oxidase A (MAO-A) and catechol-O-methyltransferase (COMT). In patients with Parkinson’s disease (PD), there is a substantial loss of dopaminergic neurons (up to 80% of dopaminergic neurons are already lost or damaged before the onset of clinical symptoms), leading to reduced reuptake of dopamine from the synaptic cleft. Consequently, the metabolism of dopamine, as a substrate for MAO-A, is decreased in presynaptic terminals. Compensatorily released dopamine is instead metabolized by monoamine oxidase B (MAO-B) located in surrounding glial cells.

Monoamine oxidase (MAO) is a class of enzymes capable of degrading monoamines. Located on the mitochondrial membrane of cells, MAO is divided into two subtypes: MAO-A and MAO-B. The two subtypes differ in the compounds they inhibit and the substrates on which they act. MAO-A primarily metabolizes serotonin and dietary amines, whereas MAO-B primarily metabolizes dopamine. Monoamine oxidase B inhibitors (MAO-BIs), by inhibiting MAO-B activity and blocking the breakdown of dopamine in the brain, and potentially offering neuroprotective effects and delaying symptom progression, have become one of the therapeutic options for Parkinson’s disease (PD).

Rasagiline effectively controls the symptoms of Parkinson’s disease (PD) by irreversibly binding to monoamine oxidase B (MAO-B), thereby inhibiting dopamine degradation in the brain and increasing dopamine levels in the synaptic cleft. Its primary metabolite is aminoindan, which avoids the risks associated with amphetamine derivatives produced by first-generation MAO-B inhibitors, while potentially offering neuroprotective activity. This medication can be used as monotherapy for primary Parkinson’s disease or as adjunctive therapy (in combination with levodopa) for patients experiencing end-of-dose fluctuations.

The drug was approved by the European Union in February 2005, received FDA approval for marketing in the United States in May 2006, submitted a marketing application in January 2014, and was officially approved by the NMPA in June 2017.

(Source: CDE)

Currently, only Qilu Pharmaceutical and Changzhou Fourth Pharmaceutical have filed under Category 4, with Qilu securing the first generic approval.

(Source: CDE)

References:

[1] Bertram & Tanzi. Thegenetic epidemiology of neurodegenerative disease. J Clin Invest2005;115(6):1449-1457.

[2] DorseyER, et al. Projected number of people with Parkinson disease in the mostpopulous nations, 2005 through 2030. Neurology. 2007; 68(5): 384-386.

[3] Zhang ZX, et al.Parkinson's disease in China: prevalence in Beijing,Xian, and Shanghai. Lancet. 2005 (365)9459:595-7.