The Burrill Report


As death rates from major diseases declined between 2000 and 2008, a grim new report finds the incidence of Alzheimer’s disease, already the sixth-leading cause of death in the United States, has risen 66 percent during that time. The report from the Alzheimer’s Association notes there are presently no treatments to prevent, cure or slow the disease and warns about a dramatic increase in the number of cases as the Baby Boom generation ages.

Already an estimated 5.2 million Americans aged 65 or older suffer from the disease. By 2030, that number is expected to grow to 7.7 million and by 2050 it could triple from today’s levels without the development of medical breakthroughs to treat the disease, the report said.

But developing such treatments has proven difficult for the pharmaceutical industry. Last year alone several promising experimental drugs to treat the disease failed late-stage clinical trails. That included Dimebon, a drug co-developed by Pfizer and Medivation, and Eli Lilly’s monoclonal antibody semagacestat, the failure of which caused some to question trying to treat the disease by developing a drug that reduces the accumulation of beta-amyloid, a toxic protein that builds up in the brain of Alzheimer’s patients. Similarly, Myriad Genetics experimental drug Flurizan failed in late-stage testing in 2008.

One problem is that the disease is still not well understood. Although there are a number of risk factors associated with the disease that include beta-amyloid accumulation, certain known genetic mutations, family history, the APOE-E4 gene, cardiovascular disease risk factors, and traumatic head or brain injury, there is still no known cause of the disease.

The toll of the disease, beyond its impact on patients and caregivers, extends to a potential economic crisis in healthcare. By 2050, the cost of Alzheimer’s in the United States is expected to rise (in current dollars) to $1.1 trillion a year from $183 billion today. Medicare and Medicaid cover about 70 percent of the costs of care.

The U.S. Food and Drug Administration has approved five drugs that temporarily slow worsening of symptoms for about six to 12 months, the report said. These drugs are effective in only about half of the people who take them.

Finding a drug to delay the onset of the disease by just five years could have dramatic effects. The Alzheimer’s Association has said doing so could cut the number of cases in half and save nearly $450 million a year by 2050.

About 75 to 100 experimental therapies aimed at slowing or stopping the progression of Alzheimer’s are in human clinical trials. Below is a selection of those drugs.


In the Pipeline: Selected Alzheimer's Drugs

Company	Ticker	Drug	Phase	Notes
Elan Johnson & Johnson Pfizer	ELN (ADR) JNJ PFE	bapineuzumab	3	The Beta-amyloid inhibitor is in an ongoing trial of patients with mild to moderate Alzheimer's disease.
Pfizer Medivation	PFE	Dimebon	3	MpTp Modulator. Pfizer said in March 2010 Dimebon failed to outperform placebo, but still in pipeline as of February 2011
Eli Lilly	LLY	solanezumab	3	Two identical trials are testing whether solanezumab will slow the cognitive and functional decline of Alzheimer’s Disease patients as compared with placebo
Baxter BioScience	BAX	Gammagard	3	In a phase 2 trial, after 18 months, patients who received Gammagard continuously averaged approximately 1.36 points higher than patients who initially received placebo using the Alzheimer's disease Cooperative Study-Clinical Global Impression of Change rating. Patients who received Gammagard continuously declined by approximately 9.15 fewer points using the Alzheimer's disease Assessment Scale-Cognitive Subscale score than patients who initially received placebo (approximately 6 point decline versus 15 point decline).
Ceregene	Private	CERE-110	2	Gene therapy designed to deliver nerve growth factor for the treatment of Alzheimer’s Disease. Ceregene said in May 2007 that a phase 1 dose was well tolerated and interim analysis suggested therapy had potential to reduce rate of cognitive decline and increase brain metabolism
Bristol-Myers Squibb	BMS	BMS-708163	2	Currently recruiting participants for a multicenter, double blind, placebo-controlled, safety and tolerability study of BMS-708163 in patients with prodromal Alzheimer's disease
Pfizer	PFE	PF-04494700	2	Receptor for Advanced Glycation Endproducts (RAGE) inhibitor currently recruiting participants for a study to evaluate the efficacy and safety of PF-04494700 in mild to moderate Alzheimer's disease.
Pfizer	PFE	SAM-531 (PF-05212365)	2	Currently recruiting patients for a phase 2 study to evaluate the relationship between plasma drug levels and receptor binding in brain using PET in healthy volunteers
Pfizer	PFE	PF-04360365 (ponezumab)	2	Currently recruiting participants for a multiple IV dose study of PF-04360365 in patients with mild to moderate Alzheimer's disease.
Elan Transition Therapeutics	ELN TTH	ELND005	2	Failed. Elan reviewing alternatives to advance the compound. In the mid-stage, placebo-controlled trial, 351 patients with mild to moderate Alzheimer's disease received the study drug for up to 18 months. Subjects with MMSE scores between 16 and 26 received ELND005 oral doses of 250 mg, 1000 mg or 2000 mg twice daily or matching placebo. The study's cognitive and functional co-primary endpoints did not achieve statistical significance.
Noscira	ZEL	Nypta	2a	Patients treated with Nypta plus an acetylcholinesterase inhibitor as base treatment showed a consistent improvement in 4 of the 5 clinical efficacy variables used. The improvement was more appreciable at the highest dose, where the change in the Mini Mental State Examination and the Alzheimer's disease Assessment Scale demonstrated a greater effect than when using cholinesterase inhibitors alone.
MorphoSys Roche	FSE:MOR ROG	gantenerumab	1	Currently recruiting patients for a phase 2 study to evaluate the effect of gantenerumab on cognition and functioning and the safety and pharmacokinetics in patients with prodromal Alzheimer's disease.
Pfizer	PFE	PF-05236812 (AAB-003)	1	Currently in a study to evaluate the safety of multiple doses of PF-05236812 in patients with mild to moderate Alzheimer's disease with patients receiving either the drug or a placebo.
Pfizer	PFE	PF-05212377 (SAM-760)	1	Currently in a study to evaluate the safety, tolerability, and pharmacokinetics of PF-05212377 administered orally.
Intellect Neurosciences	ILNS	Oxigon	1b	Oxigon was safe and well tolerated at all dose levels; that there was no relationship between the frequency, incidence, severity, onset or duration of any the adverse events: and that these were not different from those in subjects receiving placebo.
Avineuro	Private	AVN-322	1	AVN-322 is a potent and selective small molecule antagonist of the 5-HT6 receptor for treatment of Alzheimer's disease. It was well tolerated in a wide range of doses and no adverse events were observed.

March 16, 2011
http://www.burrillreport.com/article-alzheimer%e2%80%99s_toll_grows.html