Masitinib is a veterinary medicine used to treat certain cancers in animals. It is also being tested for other neurodegenerative diseases, including amyotrophic lateral sclerosis and progressive multiple sclerosis. However, its effectiveness in ALS remains to be proven.
Masitinib has achieved its main objective in a trial on Alzheimer's disease, according to the main data announced on December 16 by its sponsor, the Parisian company AB Science.
In the six-month phase 2b / 3 study involving 718 patients with Alzheimer's disease, the drug, on average, appeared to stop cognitive decline, but did not show improvement. Fewer patients have progressed to severe dementia. This confirms the results of a previous small phase 2 trial of 34 patients with Alzheimer's disease, where Masitinib stabilized cognition over six months.
While these results are encouraging, it is only so because no other drug seems to work in mild to moderate Alzheimer's disease.
AB Science started the current study in 2013 in Spain, Romania, Poland, Ukraine, Bulgaria and Greece.
Participants were on average 72 years old; about half had mild Alzheimer's disease, defined as an MMSE of 21–25, and the remainder of moderate, defined as an MMSE of 12–20.
The trial included three treatment arms: 3 mg/kg, 4.5mg/kg, and a high dose arm, 4.5mg to 6mg/kg, which had its own placebo control group.
Recruitment was slow, however, leading researchers to abandon the 3 mg / kg arm to focus on the higher doses.
The study design is unusual, it is standard in trials for mild to moderate Alzheimer's disease to require that the two primary endpoints meet the statistical cutoff. Criticism of the study design is not new for Masitinib, but it is likely the result of a group that is financially constrained and trying to move forward as quickly as possible.
The 4.5 mg / kg arm ended up with 182 participants on medication and 176 on placebo. The placebo group decreased slightly on ADAS-Cog over 24 weeks, while the treatment group improved by 1.5 points.
On the main measure, ADCS-ADL, the placebo group decreased slightly and the treatment group improved slightly. On secondary measures, the treatment group had a better trend. Treated participants were less likely to progress to severe dementia, with only 1 percent doing so, compared to 6 percent of controls.
In the high dose arm, the results were not significant. The 186-person treatment group and, oddly enough, the 91-person control group improved slightly on ADAS-Cog and ADCS-ADL. There were more than twice as many serious adverse events in the treatment group: 13% versus 5% in the control groups. These side effects did not follow any obvious pattern, being dispersed among different organ systems.
There are still questions about the mechanism of action. An anticancer drug (kinase inhibitor) having an effect on Alzheimer's disease is quite unique.
AB Science researchers believe that Masitinib may work in several ways to help the brain with Alzheimer's disease. Glial cells have received little attention in Alzheimer's disease research. Finally, Masitinib inhibits the protein kinase Fyn, which has been linked to amyloid and tau pathology, suggesting that the drug may affect these processes. Fyn is associated with T cell and neuronal signaling in development and normal cell physiology. Perturbations in Fyn often have implications in the formation of various cancers.
Company representatives have said they will begin a Phase 3 AD confirmatory trial next year.
In the next phase 3 trial, researchers will use the results of biomarker tests to examine the effects of treatment on different brain conditions. They will only test the 4.5 mg / kg dose and include more AD at an early stage. The company will also continue to develop the drug for multiple sclerosis and amyotrophic lateral sclerosis.