Drug Development Hurdles
Some 5.4 million Americans among about 36 million people worldwide have AD. These numbers are expected to balloon to 15 million Americans among 115.4 million people worldwide by 2050.
It’s fair to say the disease and its related illnesses constitute one of the last untapped markets for new blockbuster drugs. The size of the market has been estimated at $5.4 billion in 2010, set to nearly triple to $14.3 billion by 2020, according to Decision Resources.
Yet only five medicines are approved by FDA for the disease: Cognex, Aricept, Exelon, Razadyne, and Namenda. None are a cure; all treat only symptoms, and none for more than a few months. Several potential new medicines have been grounded in recent years by failed clinical trials. In January, Pfizer and Medivation ended a co-development and marketing collaboration on Dimebon (latrepirdine) after a Phase III trial did not meet either of its co-primary endpoints of improving cognition or self-care and daily function. Pfizer had paid $225 million up front and agreed to pay $500 million tied to milestones.
In 2010, Eli Lilly ended development of the peptide semagacestat after a Phase III trial showed that the gamma secretase inhibitor failed to improve disease progression. Additionally, the treatment was associated with worsening of clinical measures of cognition and the ability to perform activities of daily living. Similar Phase III failures ended development of Myriad Pharmaceuticals’ nonsteroidal anti-inflammatory drug tarenflurbil earlier that year and of Neurochem’s amyloid B antagonist tramiprosate in 2007.
“Perhaps the disease is being treated too late, when damage is irreparable?” The Lancet posited in an editorial. “The best time to treat Alzheimer’s disease is likely to be before memory loss and tissue destruction occurs, but this is hard to model in animals. That means identifying people at risk of developing the disease, perhaps because of a genetic predisposition or by measuring biomarkers.”
A key factor in the dearth of treatments for AD has been lagging federal basic research funding compared with diseases whose stakeholders have shown more activism and Washington savvy. During FY 2012, the agency expects to spend $5.451 billion on cancer research and another $3.075 billion on HIV/AIDS. That’s more than $8.5 billion combined.
By contrast NIH spent $448 million in FY 2011 on Alzheimer disease research and expects to spend about the same this year and $449 million in FY ’13. President Barack Obama has asked NIH to squeeze out another $50 million from its current budget and $80 million next year. Of the total for FY 2012, $25 million will come from ongoing research on whole genome and whole exome sequencing at the National Human Genome Research Institute. The $80 million for next year would come from the Administration’s FY 2013 budget for the Prevention and Public Health Fund, which was created by the Affordable Care Act to focus on pressing public health needs. Next year’s budget proposal also includes another $26 million for other agencies for caregiver support, education, and public awareness.
Lack of funding isn’t the only hurdle for AD research. So too is the difficulty of getting patients and their families to participate in clinical trials. The National Plan calls for increasing enrollment in trials “through community, national, and international outreach.”