Aribio's 'Oral Dementia Treatment' Submits Phase 3 Clinical Trial IND in China Following Hanmi

Aribio, developing the oral Alzheimer's dementia treatment 'AR1001,' is accelerating the global Phase 3 clinical trial 'Polaris-AD.'

[Photo by Aribio]

On the 7th, Aribio announced that it has completed the submission of the Phase 3 clinical trial plan (IND) for AR1001 to the Center for Drug Evaluation (CDE) under the National Medical Products Administration (NMPA) of China.

The Polaris-AD trial is planned to enroll a total of 1,250 participants, including 100 to 150 in China, 150 in Korea, 600 in the United States, and 400 in Europe. Domestically, IND approval was obtained from the Ministry of Food and Drug Safety last month, and in the United States, IND approval was already granted by the Food and Drug Administration (FDA) last year, with patient dosing currently underway.

Jaejun Jung, CEO of Aribio, stated, "We decided to include China in the ongoing global Phase 3 trial to establish a foothold in one of the world's major markets." He added, "Although there were challenges in the IND submission due to NMPA's strict management and regulatory processes, the strong commitment to technology transfer and commercialization with Chinese partner companies, which has been actively progressing recently, greatly influenced the IND application for Phase 3."

Following the IND submission in China, preparations are underway to submit an IND in Europe within this year. The company explained that in June, it applied for Scientific Advice on the AR1001 European Phase 3 clinical protocol to the Committee for Medicinal Products for Human Use (CHMP) under the European Medicines Agency (EMA), and received a positive opinion agreeing with the clinical protocol and overall clinical design for approval.

Photo by Lee Chunhee

AR1001 aims to be an oral dementia treatment with multiple mechanisms of action. It is explained to have efficacy in inhibiting dementia progression and improving patients' memory and cognitive function through strong phosphodiesterase (PDE) 5 inhibition. The mechanism is broadly threefold. First, it suppresses the intracellular production of amyloid-beta (Aβ) protein, one of the key factors in Alzheimer's dementia. While antibody therapies, which dominate current dementia treatments, remove extracellular Aβ accumulated in the brain, AR1001, as a synthetic chemical drug, has a smaller molecular structure that penetrates cells and removes Aβ via autophagy, thereby inhibiting its accumulation.

Additionally, it activates the cAMP response element-binding protein (CREB) signaling pathway within brain neurons to inhibit neuronal death caused by toxic cells and promote the generation of new cells. There is also an extracellular mechanism: it activates the Wnt signaling pathway involved in cell proliferation or differentiation, enhancing synaptic plasticity by ensuring neurotransmitters function properly.

In the previous Phase 2 trial, the AR1001 30 mg monotherapy group showed improvements of 3.5 points at week 26 and 5.8 points at week 52 in the primary efficacy endpoint, the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) 13. Notably, the mild patient group showed an improvement of up to 8.7 points, raising expectations for favorable outcomes in Phase 3.

This Phase 3 trial will be conducted based on the Phase 2 results, administering AR1001 30 mg to patients aged 55 to 80 with mild cognitive impairment (MCI) or mild Alzheimer's dementia, which are pre-dementia stages. The primary efficacy endpoint will apply the Clinical Dementia Rating (CDR) - Sum of Boxes (SB), identified as the most appropriate primary endpoint in the FDA's dementia drug guidelines.

James Rock, Chief Clinical Operations Officer (CCOO) of Aribio's U.S. branch, said, "To efficiently operate and succeed in the global Phase 3 trial, we have continuously recruited talented personnel with extensive clinical experience to both the Korean headquarters and the U.S. branch, establishing all necessary systems." He added, "As the final trial is now in full swing, we are receiving ongoing contact from patients and families recognizing AR1001's efficacy not only in Korea but also in the United States, and all employees are working hard to ensure this drug can help patients as soon as possible."

This content was produced with the assistance of AI translation services.