Eli Lilly sunk a lot of resources into its Alzheimer's drug semagacestat until results came in from its Phase III trials. It appeared to have worsened the condition of patients taking the drug. So, in August 2010, Lilly wrote its obituary for semagacestat and halted all development.
The biopharmaceutical company Medivation made it to Phase III with its Alzheimer's drug Dimebon before it crashed and burned, making it to one of 2010's Top 10 list of Phase III failures. The treatment was actually an old drug used to treat hay fever in Russia. Medivation announced that Dimebon failed to demonstrate a statistically significant response compared with placebo. The failure was a disappointment to the Alzheimer's community and also to Pfizer, which had sunk $115 million into an upfront payment to license the therapy.
Bapineuzumab is an antibody to the beta-amyloid plaques believed to contribute to Alzheimer's disease. The drug is being co-developed by Elan, Johnson & Johnson and Pfizer. There have been some reports of brain swelling during trials. However, there are 14 ongoing Phase III trials in more than 10,000 patients and results of some completed studies may be available in late 2012.
Not discouraged by the failure of Semagacestat, Eli Lilly is plowing ahead with its Alzheimer's drug solanezumab. The drug is another beta-amyloid antibody investigated as a potential treatment to slow the progression of mild to moderate Alzheimer's disease. Eli Lilly is reporting that one patient enrolled in a study of solanezumab experienced temporary brain swelling; however, it's not clear yet whether the subject was receiving the drug or a placebo. The patient was able to resume treatment after the issue had subsided.
The German companies MorphoSys AG and Roche have used MorphoSys's HuCAL (Human Combinatorial Antibody Library) to isolate a specific human antibody that could target and dissolve Aß plaques. Preclinical tests show the MorphoSys/Roche antibody gantenerumab has the ability to dissolve these plaques in vitro. And it's able to cross the blood-brain barrier in laboratory animals. Gantenerumab is currently in Phase I clinical trials; it is expected that Phase II studies will start recruiting patients in the first half of 2011.
Baxter BioScience is conducting tests to determine if Immune Globulin Intravenous (IGIV) can slow the rate or prevent the decline of dementia symptoms in individuals with mild-to-moderate Alzheimer's disease.
Ceregene is doing a study of its CERE-110 gene delivery in subjects with mild to moderate Alzheimer's disease.
Much of the current Alzheimer's disease research is devoted to finding biomarkers for early detection. Figure out the underlying pathologies associated with Alzheimer's disease, like formation of amyloid plaques, and maybe you can get as much of a decade-long jump on the disease before it begins affecting memory.
- GE Healthcare and Johnson & Johnson are teaming up on a new project aimed at finding pre-symptomatic biomarkers for Alzheimer's disease.
- New guidelines are being developed to identify biomarkers through brain scans, MRIs and spinal taps.
- Takeda Pharmaceuticals and Zinfandel Pharmaceuticals are getting together to see if they can validate a biomarker known as TOMM40 as a test for Alzheimer's disease in older adults with normal cognition. The two companies will study pioglitazone, an active ingredient of Takeda's Actos (pioglitazone HCl), in connection with the TOMM40 biomarker and Alzheimer's.
- The European Medicines Agency is now taking comments on the first clinical biomarker the agency has approved for use in humans. The EMA responded favorably to the use of two cerebral spinal fluid biomarkers for use in clinical trials in pre-dementia Alzheimer's disease. The opinion is open for comments until March 23 and was requested by Bristol-Myers Squibb. Low levels of the protein Aβ1-42 and high levels of the protein T-tau in the cerebrospinal fluid of patients with mild cognitive impairment appear to be linked to a higher risk of developing Alzheimer's disease-related dementia.
- And a new marker for Alzheimer's could point the way to a more effective treatment. Investigators at the Gladstone Institute of Neurological Disease in San Francisco have zeroed in on a neurotransmitter called EphB2, which is depleted in patients. The researchers found when they cut the level of EphB2 in mice, they quickly developed the kind of memory problems that plague patients. And when they pushed levels back up, the symptoms disappeared.
- And finally, since stem cells are constantly in the news these days in many contexts, the Alzheimer's angle to the story comes from Northwestern University's Feinberg School of Medicine in Chicago, where researchers are looking into using stem cells to replace neurons lost to Alzheimer's. One of the first things to go in Alzheimer's patients is their basal forebrain cholinergic neurons (BFCN), associated with deficits in spatial learning and memory. The death of these neurons leads to memory-retrieval problems.
So, scientists are looking closely at how to replace lost BFCN. A new study published in the journal Stem Cell looks at the potential of human embryonic stem cells to be transformed into BFCN. These homegrown neurons could be used to test possible Alzheimer's drugs or could potentially replace the cells lost to Alzheimer's.