Breakthroughs in Alzheimer Disease

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A pair of trials related to Alzheimer disease recently released big news: NovoNordisk decided to move its recently launched type 2 diabetes drug semaglutide into a phase 3 study, and AB Science SA shared the results from a phase 2B/3 study evaluating masitinib in Alzheimer disease.

NovoNordisk’s type 2 diabetes (T2D) drug, semaglutide, will be the first-to-market oral GLP-1RA in T2D. However, after the large number of failures in Alzheimer disease trials in 2019, several key opinion leaders believe NovoNordisk will face a tough battle when entering into Alzheimer disease market.¹

Valentina Gburcik, PhD, Senior Director of Cardiovascular and Metabolic Diseases, Gender Health and Digital at GlobalData, had this to say on semaglutide: “Due to the growing unmet needs in the Alzheimer’s space, which has not seen any major medical breakthroughs over the past decade, and the increasing evidence of a potential therapeutic role for GLP-1, oral semaglutide may be able to secure its position in a yet another lucrative market if found to be efficacious in challenging Alzheimer’s clinical trials. However, the drug may face fierce competition from a number of novel therapies entering the Alzheimer’s market over the next several years.”¹

On the topic of masitinib, AB Science SA presented data confirming that masitnib’s mode of action has a potential synergistic effect and 4 targets. The 4 targets of masitinib in Alzheimer disease are:

1. Modulation of microglia: masitinib modulates microglia activity through inhibition of the CSFR-1 kinase and is involved in the neuroinflammatory processes commonly associated with Alzheimer disease.

2. Protecting synapses: Alzheimer disease alters synapses, and masitinib has been shown to promote recovery of synaptic markers in mouse models.

3. Inhibiting the tau protein: masitinib inhibits the FYN kinase, a kinase that mediates tau phosphorylation, and also prevents the accumulation of amyloid fibrils in the hippocampus, as shown in mouse models.

4. Control of mast cell activity: masitinib blocks mast cells activity through inhibition of the c-Kit, LYN, and FYN kinases. Mouse models showed that mice depleted of mast cells do not develop symptoms of Alzheimer disease.

In a transgenic mouse model, masitinib was able to restore cognitive impairment and restore ability to perform navigation strategy in the Morris Water Maze experiment. It could also exert a neuroprotective effect against synaptic loss.

“Study AB09004 was a well-designed phase 2b/3 as it compared masitinib on top of standard of care treatment versus the standard of care. These data are very encouraging and may provide new hope for patients with Alzheimer’s disease,” Bruno Dubois, MD, PhD, professor of neurology at the Neurological Institute of the Salpétrière University Hospital at Paris and coordinating investigator of the study, said to the press.²

These announcements point to big changes on the horizon for the treatment of Alzheimer disease. Further discoveries and products will hopefully bring clinicians and researchers a step closer to a cure. 

References

1. GlobalData. NovoNordisk’s Rybelsus a game changer in T2D but may face a tough road ahead as it strides into Alzheimer’s space. News release. December 18, 2020. https://www.globaldata.com/novonordisks-rybelsus-game-changer-t2d-may-face-tough-road-ahead-strides-alzheimers-space/

2. AB Science. AB Science communicates the results from phase 2B/3 study evaluating masitinib in Alzheimer’s disease. News release. GlobeNewswire. December 18, 2020. https://www.globenewswire.com/news-release/2020/12/18/2147549/0/en/AB-Science-communicates-the-results-from-phase-2B-3-study-evaluating-masitinib-in-Alzheimer-s-disease.html