Cassava Sciences’ simufilam (code name: PTI-125), an experimental drug for Alzheimer’s disease, used to be called “a miracle treatment” with worldwide attention.
However, the U.S.-based company is struggling to enroll patients for phase 3 trials due to serious questions about the reliability of the latest research data.
Despite the controversy, the Korean regulator recently authorized a phase 3 study of simufilam.
On Tuesday, the Ministry of Food and Drug Safety granted the nod to Premier Research Group Limited, a clinical research organization (CRO), to conduct the phase 3 trial in Korea.
The randomized, double-blind, placebo-controlled, parallel-group, and 76-week REFOCUS-ALZ study will evaluate the safety and efficacy of two doses of simufilam in patients with mild to moderate Alzheimer's disease.
The Korean trial will occur at major tertiary hospitals, including Asan Medical Center, Korea University Anam Hospital, Hanyang University Medical Center, and Inha University Hospital.
The REFOCUS-ALZ study design, registered on ClinicalTrials.gov, will recruit 1,083 patients, but it does not show how many Korean patients are included.
The problem, however, is that simufilam is under fire for irregularities in research outcomes in the U.S.
On April 18, the New York Times reported that several studies of simufilam were retracted or questioned by scientific journals and that Cassava was criticized for opaque study results.
In the summer of 2021, Cassava released the results of a small clinical trial and said simufilam was effective in improving cognition in Alzheimer’s patients.
After administering simufilam to 50 patients with mild to moderate Alzheimer’s for nine months, the patient’s ADAS-Cog score, a measure of cognitive function, went up by about three points, the company said.
Such data attracted enormous attention from investors. As a result, cassava’s stock price once shot up by 1,500 percent, and the company’s value was almost $5 billion last summer.
However, the controversy over simufilam began when many scientists pointed out Cassava’s study flaws. They said the trial lacked the placebo group and follow-up period and was inadequate to prove the recognition improvement effect. Some experts even said the company manipulated scientific results.
In December, the Journal of Neuroscience officially questioned the integrity and accuracy of two papers on simufilam’s effect, authored by Hoau-Yan Wang, a professor at the City University of New York, Cassava’s chief researcher, and Lindsay H. Burns, the company’s another chief scientist.
In March, the journal Neurobiology of Aging also expressed concerns about another paper written by Wang and Burns that contained the key content for simufilam’s treatment hypothesis.
On March 30, the scientific journal PLoS One said it retracted five papers by Wang after a five-month investigation. Two of them, co-written by Burns, were about a brain protein targeted by simufilam.
“According to Cassava, simufilam restores the normal shape and functioning of a protein called filamin A that becomes warped in the brains of people with Alzheimer’s disease, and thereby slows dementia and improves cognition,” the New York Times reported. “But Alzheimer’s experts said they knew of no independent studies that supported this hypothesis or would explain the results.”
The newspaper quoted Thomas Südhof, a Nobel laureate and neuroscientist at Stanford, saying that Cassava’s theories “are not in the mainstream of the field, and to me, they seem implausible and contrived.”
Such negative responses led to a significant fall in Cassava’s stock, and the company is struggling to enroll patients for phase 3 trials of simufilam.
Cassava is working on two phase 3 trials – RETHINK-ALZ and REFOCUS-ALZ – and aims to recruit 1,750 patients.
However, Cassava recruited only 120 patients for phase 3 trials, according to Cassava’s first-quarter report released on May 5.