Breakthrough! Phase III Clinical Study of the Chinese New Drug for Alzheimer's Disease Met the Endpoint and is Waiting for Marketing

Shanghai Green Valley Pharmaceutical (Green Valley) announced on the 17^th that the Phase III clinical study of "Sodium Oligomannurarate (GV-971)", a new drug for Alzheimer’s disease (AD) jointly developed by it, Ocean University of China (OUC), and Shanghai Institute of Materia Medica, Chinese Academy of Sciences (SIMM), successfully met the endpoint, which means that this drug will be marketed soon. This can be called a "cardiac stimulant" to the AD drug market that has long been sluggish. Next, I’d like to talk about the following points of attention.

I. Main characteristics of Sodium Oligomannurarate (GV-971)

GV-971 is a marine oligosaccharide molecule originally extracted by researchers of OUC from algae and it has later been deeply developed by SIMM and Green Valley. It has been 21 years from the extraction to end of Phase III clinical study thereof. Unlike the traditional AD drugs, GV-971 can bind to multiple Aβ (amyloid beta) sites and fragments and in its different states and thus inhibits Aβ aggregation and destabilizes aggregated fibrils into monomeric nontoxic forms. And according to relevant research, GV-971 can also remodel immune homeostasis by regulating intestinal flora, and reduce neuro-inflammation, to reach treatment of AD. It is because of the unique multi-targeted mechanism of action of GV-971 that it has an irreplaceable advantage over other AD drugs.

II. Introduction and incidence of AD

AD is a neurodegenerative disease originally discovered by the German psychiatrist Alois Alzheimer, hence the name. Such disease has main manifestations of memory impairments and cognitive decline, and even loss of the self-care ability in life, which greatly affects patients’ life quality.

The causes of AD are not completely clear medically, and there are only speculations and hypotheses obtained based on observations. The existing causes include gene, neurotransmitter (acetylcholine decrease), Aβ precipitation, microtubule-associated protein (Tau protein), metal, virus, and immune system disorder, etc.

There is a large number of AD patients. According to statistics of the Alzheimer's Disease International, the number of global AD patients has reached 50 million, and this figure is rapidly rising as the global population ages.

III. Current market situation of AD drugs

As mentioned above, the causes of AD are not completely clear, therefore, the current situation of drug treatment is not positive, and the drug development therefor is very slow. There are only a few drugs approved by FDA for AD: clinical drugs mainly include acetylcholinesterase inhibitors represented by donepezil and N-methyl D-aspartate (NMDA) receptor antagonists represented by memantine at present, however, most of them can only help improve patients’ quality of life but have no significant effect on the course or remission of patients.

Directions of the AD drugs currently marketed or in development can mainly be classified into the followings: 1. Acetylcholinesterase inhibitors (AchEIs), such as the first marketed AD drug tacrine; 2 NMDA receptor antagonists, such as memantine; 3. Anti-Aβ drugs and immune drugs targeting Aβ, such as GV-971 that met Phase III clinical study endpoint this time; 4. β-secretase inhibitors, such as AZD-3293 jointly developed by AstraZeneca and Eli Lilly; 5. Tau protein associated drugs, including Tau-protein immune drugs, Tau-protein kinase inhibitors, and Tau protein aggregation inhibitors, with TRx0237 (for example) that is in fast development already in Phase III clinical trial; 6. Inhibitors of receptor for advanced glycation end products (RAGE), such as TTP488 that is already in Phase III clinical trial.

IV. Words in the end

The complicated pathogenesis of AD has not been thoroughly studied and development of drugs therefor has long been stagnant, with very large resistance encountered in the R&D, which hurts confidence of pharmaceutical enterprises to some degree, for example, a new β-secretase inhibitor (BACE) co-developed by AstraZeneca and Eli Lilly last month was abandoned because the drug was unlikely to meet the R&D objective.

The number of global AD patients increases as the global population is aging, which brings huge social pressure and economic burden to the disease control and prevention of each country. It’s reported that the expenses used for AD treatment reach above USD 200 billion a year in the U.S. alone, and this huge amount only leads to quite limited effects because there is no efficient AD drug. Therefore, we can imagine how urgent the need for efficient AD drug is.

However, we can see that the drug researchers do not stop their development of AD drugs in the face of the huge resistance, and have made some breakthroughs recently. For example, TNX-102 SL under Tonix Pharmaceuticals has recently received the fast track designation from the FDA for treatment of agitation in AD; this, plus the Phase III clinical study of GV-971 successfully meeting the endpoint, has brought new hopes to AD treatment. As revealed by Green Valley, it will file the marketing application of GV-971 to SDA (State Drug Administration of China, formerly, CFDA) within the year. Let’s wait and see.

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