Alzheimer's was in the spotlight this week as investigators gathered at the annual Alzheimer's Association International Conference in Boston to ponder the latest data available on a field of candidates trying to make some headway against one of the toughest disease targets in the industry. Some of the highlights:
- In one of the few bright spots at the conference, Lundbeck and Otsuka say they tracked a clear, statistically significant improvement in the combo arm of a Phase II study comparing Lu AE58054/donepezil against donepezil and a placebo. The primary endpoint was ADAS-Cog at Week 24--which measures the severity of the most important symptoms. The drug failed to distinguish itself for secondary endpoints on two other measures, though the companies say the trial was not designed to demonstrate statistically significant improvements on either of those measures. The partners are now preparing a 3,000-patient Phase III study, a virtual Valley of Death for this field in recent years. Story
- Baxter International ($BAX) showed up to review its late-stage data on IV Gammagard, the last in a string of Phase III flops in patients with mild and moderate Alzheimer's. As already reported, Gammagard flunked the two key endpoints for cognitive and functional abilities among mild-to-moderate patients. But the investigators in the study refuse to give up, noting that they're continuing to explore subpopulations in Alzheimer's who might yet prove to clearly benefit from the therapy. In particular they are concentrating on ApoE4 carrier patients. "The signals identified in the clinical and biological markers in select subgroups in this analysis are intriguing and help contribute to a better understanding of this disease," said Dr. Norman Relkin, of Weill Cornell Medical College and GAP Study leader. Release
- ApoE4 is also a central focus for Chiesi, which has been studying CHF5074, a gamma-secretase modulator, in a small human study of patients with mild cognitive disorder. The drug is designed to target microglia, immune cells that can run amuck after being exposed to amyloid beta, the toxic protein that many believe is the primary culprit in the disease. And investigators say they saw some encouraging responses from patients who were given various cognitive tests--though they caution that this new approach is still at a very early stage of development. "We think that this medication may be a start, the first step--perhaps a baby step--in preventing the memory loss that of course is the classic hallmark that Dr. Alzheimer described in the early 1900s," said Dr. Joel Ross, according to a report from Clinical Neurology News. Report
- Merck ($MRK), meanwhile, seized center stage with Phase Ib data on MK-8931. To determine if it's working, Merck checked on the flow of amyloid beta 40 and 42, key biomarkers for the study, in cerebral spinal fluid. Over the course of 7 days of treatment, investigators say they could see a noted, dose-dependent response in protein levels in the fluid. For the top 60 mg dose, investigators say they found an 84% drop in ab40, according to a spokesperson for Merck. There was an 81% drop for ab42. That drug is now in the first leg of a Phase II/III trial. Report
- Finally, investigators at USC are laying out plans for a Phase I study of Allopregnanolone (also known as Allo), a neurosteroid found in the brain and bloodstream. They say that in earlier studies it has "shown promise as a potential regenerative therapy to promote brain cell creation and improve cognitive function in older animals and animal models of Alzheimer's disease." "Allopregnanolone is a well-characterized agent with a very promising track record of promoting neural stem cell generation and restoring cognitive function in animal models of Alzheimer's," said USC's Roberta Brinton. "We consider Allopregnanolone a first in class regenerative therapeutic for MCI and Alzheimer's. Our hope is that, through further research, we will add Allo to the roster of Alzheimer's treatments. Release