Potential First: Pill for Lewy Body Dementia Heads to a Phase 3 Trial
After a rocky start and a bad batch of pills, CervoMed’s experimental drug for dementia with Lewy bodies is making its way through trials. It could become the first treatment to slow this disease.
Lewy body dementia is one of the most common forms of dementia, accounting for 20 to 30 percent of all cases worldwide. But scientists know relatively little about LBD and there are currently no approved treatments to stop or slow the disease.
CervoMed’s experimental pill, neflamapimod, is hoping to change that. Designed to treat dementia with Lewy bodies — a form of LBD that causes cognitive fluctuations and hallucinations — the drug showed promise in a Phase 2 trial, and as a result is soon heading to a definitive Phase 3 study.
More than 50 percent of people with LBD also have beta-amyloid plaques in their brain, signs they may have Alzheimer’s as well. Unlike previous studies, this trial also checked to see how well the drug worked in people who didn’t have any signs of Alzheimer’s alongside their dementia with Lewy bodies.
“Dementia with Lewy bodies has been understudied in terms of clinical trials and therapeutic development,” Dr. David Irwin, a neurologist at the University of Pennsylvania, who wasn’t involved in the research, told Being Patient. The changes detected in this trial, Irwin said, suggest that the drug could have clinically meaningful impacts on day-to-day function.
If successful, it would become the first disease-modifying treatment ever developed for dementia with Lewy bodies.
What is neflamapimod?
CervoMed’s neflamapimod is a small molecule drug that stops a key domino in the inflammation and cell death cascade, called the p38ɑ kinase protein. As a result of blocking this pathway, it prevents synaptic dysfunction — impaired communication between brain cells — slowing the progression of dementia with Lewy bodies.
The drug was also tested for Alzheimer’s but failed to slow cognitive decline. A spokesperson for the company explained that people with Alzheimer’s “often have more permanent damage and cell death in the brain, especially in areas related to memory, which is harder to reverse.”
In its first Phase 2 study, participants who took the drug for 16 weeks showed slower disease progression, and in those with low levels of Alzheimer’s biomarkers, it appeared to work even better.
What did the Phase 2b study find?
The 159-person study was split into two phases. In the initial 16-week phase, participants were randomized to receive either neflamapimod or a placebo. Participants and researchers in the study did not know who got the actual drug.
In contrast to a previous Phase 2 study, the drug this time didn’t slow down disease progression. The researchers discovered that the neflamapimod pills came from an older batch with reduced potency. As a result, the drug didn’t reach high enough levels in the body to have an effect.
In the 32-week extension phase, all participants were offered the drug — either from the old batch or a newer batch of pills. The researchers looked at changes in a 16-point scale of cognitive and functional abilities, called the Clinical Dementia Rating Sum of Boxes Scale (CDR-SB), where a 0.5 point change is considered noticeable and meaningful for patients and caregivers.
After 32 weeks:
- People taking the newer batch had a 51 to 54 percent lower risk of declining by 1.5 points or more and progressing to the next stage of the disease.
- The benefits were greater among those with low levels of an Alzheimer’s blood biomarker as their risk of disease progression dropped by to 67-75 percent.
- Participants with low levels of Alzheimer’s biomarkers who switched from placebo to a newer batch of pills improved by 1.12 points, while those who switched from placebo to the old batch showed no change.
Dr. John Alam, CEO of CervoMed, told Being Patient that those taking the new batch of the drug were also up to 75 percent less likely to progress to the next stage of the disease during the study.
Implications for Alzheimer’s
Irwin called the trial “innovative” and “exciting” because they stratified patients based on Alzheimer’s blood biomarkers. “That’s fairly unique compared to other studies,” he said. Accounting for these biomarkers was important as people with Alzheimer’s-related amyloid plaques didn’t respond as well to the drug.
“From a patient and caregiver perspective the implications of these results are profound,” Alam said. Typically, people with the disease progress rapidly, with 50 percent deteriorating within six months. If the drug works well in Phase 3 trials, he said, it could cut that down substantially. “Adding two to three years of independence and the ability to stay at home would be huge.”
The company is finalizing its upcoming trial with the FDA, but they anticipate it will start next year. The trial will last about 24 weeks and include about 300 participants with low levels of Alzheimer’s blood biomarkers.
“I’m guardedly optimistic,” said Irwin. If the Phase 3 trial is successful, he said, it could become “a catalyst for more interest” in developing new treatments for dementia with Lewy bodies.
