The news comes as a bitter disappointment to patients and families desperately seeking a treatment for this progressive, incurable disease.
Given strong results of the prior, midstage study, some doctors thought or at least hoped Dimebon might be able to stop or reverse the mind-robbing disease, which would be a first. Already, about 5.3 million Americans have Alzheimer's disease, and it strikes nearly a half million new patients a year, mainly as people hit their 70s or 80s. In 2050, up to 16 million people are estimated to have Alzheimer's disease.
Dimebon was expected to at least lessen symptoms more than the existing drugs. Dimebon works differently than the four Alzheimer's drugs already on the market, which act on particular chemicals in the brain to improve nerve cell function. So Dimebon could have been used along with any one of those to ease symptoms even more. Dimebon was seen as a probable blockbuster, given the desirability of any drug that can delay worsening of symptoms and the need for expensive nursing home care.
In 2007, expectations for Dimebon, an old antihistamine, soared on results of a positive Phase 2 trial in AD patients in Russia. Dimebon appeared not only to slow cognitive decline, but even to improve cognition.
Even though this current Phase 3 study has failed it does not necessarily mean it’s the drug; it could have been the trial design, or something else. Let’s take a look at the studies and history behind the experimental Alzheimer's drug Dimebon and what the latest findings may mean for Dimebon’s future in fighting Alzheimer’s disease.
The experimental Alzheimer’s drug Dimebon showed positive effects. May 2007. In a randomized, double-blind, placebo-controlled study conducted in Russia, the experimental Alzheimer's drug Dimebon showed positive effects on all five clinical endpoints tested. The treatment resulted in statistically significant improvement over the placebo group and over baseline for five standard clinical tests of memory, global function, cognition, daily functioning, and behavior.
Dimebon appeared safe and well tolerated. Serious adverse events occurred in 2 percent of treated patients and 7 percent in the placebo group. Dry mouth was the major side effect, but the investigators also saw increases in depression and insomnia.
Experimental Alzheimer’s drug Dimebon is still going strong. June 2007. At 12 months, the researchers still noted a clinical improvement above baseline in the treated group on memory and the cognition. On activities of daily living and behavior problems, the treated patients had returned to baseline after an initial improvement at 6 and 9 months, but the placebo group deteriorated. Global function stayed stable or improved in 69 percent of treated patients. On all five endpoints measured, Dimebon maintained an improvement over placebo. The drug’s good safety profile was unchanged.
Experimental Alzheimer’s drug Dimebon show improvements in behavior. April 2008. Data was presented to suggest that behavioral symptoms, including depression, apathy, hallucinations, and irritability, stabilized in patients with mild to moderate AD who took the drug for one year. This had the added bonus of reducing caregiver stress, which is often a key factor in the decision to institutionalize the patient.
Dimebon’s benefits seem to hold. July 2008. In a six-month Russian trial of 183 patients, Dimebon improved mild to moderate AD patients in all five of the study’s outcome measures (four cognitive, one global). What’s more, Dimebon’s benefits seemed to hold, and by some measures even increase, through the trial’s six-month blinded extension. These persistent benefits distinguish the small-molecule drug from existing approved therapies for mild to moderate AD—none of which have shown increasing improvement past 12 months.
Dimebon has emerged as a contender to become the first Alzheimer's disease drug with stronger, more lasting benefit than any of the drugs currently available. August 2008. An oral antihistamine has emerged as a contender in the race to become the first Alzheimer's disease drug with stronger, more lasting benefit than any of the drugs currently available. Dimebon drew notice for its ability to improve AD patients for at least 12 months on all of five cognitive measures in a recently published Russian trial.
The one side effect reported more frequently in the treatment group was depression. This depression was self-reported, not measured by depression scales, raising the question of whether people might become more depressed as their cognition improves slightly and they regain insight into their still-difficult condition. Another hint that Dimebon functions differently from current AD drugs came from its side effect profile in human studies: less than 3 percent of clinical trial participants who took Dimebon have reported gastrointestinal problems.
It looks like the Dimebon might have both symptom-improving and disease-modifying action. October 2009. Dimebon appeared to stave off clinical decline in mild to moderate Alzheimer's patients in a Phase 2 trial, and even manage some improvement. Although Dimebon reduces mitochondrial vulnerability to stress, it is not clear how it does this or whether it has any clinical significance. The crucial test for Dimebon will be whether the clinical data holds up. There are several Phase 3 trials currently underway for patients with mild to moderate and moderate to severe AD and Huntington disease.
The results of the first U.S. Phase 2 trial for Dimebon are finally out in print. February 2010. Dimebon was safe and well tolerated by the 46 people who received it. And over a 90-day treatment period, people taking Dimebon gained approximately one point on the Mini-Mental State Examination.
Dimebon failed to have any significant effect in two co-primary and several secondary outcome measures. March 2010. The drug’s sponsors released highly anticipated data from the Phase 3 CONNECTION study. Dimebon failed to have any significant effect in two co-primary and several secondary outcome measures. The results were unexpected and we are disappointed, especially for all these patients with Alzheimer's and their caregivers.
The randomized, double-blind, placebo-controlled trial recruited 598 patients who were not taking other anti-dementia drugs. The co-primary endpoints were cognition and global function. According to information released, after six months of treatment, there was no significant difference between either drug group and the controls. The secondary endpoints fared no better. On the Mini-Mental State Examination, another measure of cognition, the placebo group actually outperformed the drug groups. On the Neuropsychiatric Inventory, the Dimebon group showed a slight improvement over placebo. In terms of function, neither the placebo nor the Dimebon groups showed any significant change from baseline in the Alzheimer’s Disease Cooperative Study-Activities of Daily Living.
Some researchers were quick to point out that the study was not a complete failure, noting that neither the placebo group nor patients taking Dimebon worsened. Therefore, you can’t really say that the drug failed. Other researchers found it harder to see a silver lining.
What Does the Future Hold for the Experimental Alzheimer’s drug Dimebon
The March 2010 results don't necessarily spell the end for Dimebon. Medivation and Pfizer, the world's biggest drug maker by revenue, are continuing three ongoing studies that could prove Dimebon helps patients in combination with other Alzheimer's drugs or when used for a longer period. Pfizer said it was evaluating the data to determine next steps for the development of Dimebon.