Skip to main content

Tarenflurbil for Alzheimer Disease: A novel agent meets with great disappointment

The current issue of JAMA reports on the largest trial ever conducted for a drug designed to slow the progression of Alzheimer Disease (AD). The study examined the impact of Tarenflurbil, a novel secretase modulator that reduces the concentration of toxic forms of B-amyloid. B-amyloid is more likely to be present in the brains of persons with AD, and most believe amyloid deposition plays a central role in the pathogenesis of AD. (Though there are some who question the amyloid hypothesis.)

Tarenflurbil showed great promise in mouse models and in a phase 2 study in humans. This very well powered study randomized 1684 patients with mild AD (MMSE 20-26) to Tarenflurbil or placebo, and compared a number of outcomes over 18 months. The key findings:

  • Tarenflurbil had no impact in terms of delaying the decline in cognitive function
  • Tarenflurbil had no impact in terms of delaying declines in physical function
  • Tarenflurbil had no impact in terms of improving quality of life
  • Tanenflurbil had no impact on caregiver burden
  • Tarenflurbil was associated with several side effects, and rates of discontinuing therapy were significantly higher than with placebo

There was much reason to invest hope in Tarenflurbil, because it is the first agent to be tested in a large scale clinical trial to directly interfere with a process thought to be linked to the progression of AD. Unfortunately, this study is quite convincing that this agent does not improve outcomes in mild AD.

That leaves us with the current agents, acetocholine esterase inhibitors and memantine. The extent of benefit from these agents is somewhat controversial. Most of my colleagues in the UCSF Geriatrics Division believe the benefits are generally quite small, with side effects that are underrated. The most beneficial treatments for AD, as discussed in a recent post, are team based interventions that have major psychosocial components, including a focus on caregivers.

Comments

Dan Matlock said…
Thanks for another great summary Ken. Perhaps this is evidence that the Tauists (Tau protein scientists) are more likely correct and the BAPtists (Beta Amyloid Protein scientists) are wrong.

Eventually, I suspect medical science will find a drug that slows the progression of AD. That will be a fascinating discussion on many levels. Imagine an AD prevention drug - $2/day, taken by everyone over the age of 45.

Popular posts from this blog

Geroscience and it's Impact on the Human Healthspan: A podcast with John Newman

Ok, I'll admit it. When I hear the phrase "the biology of aging" I'm mentally preparing myself to only understand about 5% of what the presenter is going to talk about (that's on a good day).  While I have words like telomeres, sirtuins, or senolytics memorized for the boards, I've never been able to see how this applies to my clinical practice as it always feels so theoretical.  Well, today that changed for me thanks to our podcast interview with John Newman, a "geroscientist" and geriatrician here at UCSF and at the Buck Institute for Research on Aging.

In this podcast, John breaks down what geroscience is and how it impacts how we think about many age-related conditions and diseases. For example, rather than thinking about multimorbidity as the random collection of multiple different clinical problems, we can see it as an expression of the fundamental mechanisms of aging. This means, that rather than treating individuals diseases, targeting …

The Dangers of Fleet Enemas

The dangers of oral sodium phosphate preparations are fairly well known in the medical community. In 2006 the FDA issued it’s first warning that patients taking oral sodium phosphate preparations are at risk for potential for acute kidney injury. Two years later, over-the-counter preparations of these drugs were voluntarily withdrawn by the manufacturers.  Those agents still available by prescription were given black box warnings mainly due to acute phosphate nephropathy that can result in renal failure, especially in older adults. Despite all this talk of oral preparations, little was mentioned about a sodium phosphate preparation that is still available over-the-counter – the Fleet enema.

Why Oral Sodium Phosphate Preparations Are Dangerous 

Before we go into the risks of Fleet enemas, lets spend just a couple sentences on why oral sodium phosphate preparations carry significant risks. First, oral sodium phosphate preparations can cause significant fluid shifts within the colon …

Length of Stay in Nursing Homes at the End of Life

One out of every four of us will die while residing in a nursing home. For most of us, that stay in a nursing home will be brief, although this may depend upon social and demographic variables like our gender, net worth, and marital status. These are the conclusions of an important new study published in JAGS by Kelly and colleagues (many of whom are geripal contributors, including Alex Smith and Ken Covinsky).

The study authors used data from the Health and Retirement Study (HRS) to describe the lengths of stay of older adults who resided in nursing homes at the end of life. What they found was that out of the 8,433 study participants who died between 1992 and 2006, 27.3% of resided in a nursing home prior to their death. Most of these patients (70%) actually died in the nursing home without being transferred to another setting like a hospital.

 The length of stay data were striking:

the median length of stay in a nursing home before death was 5 months the average length of stay was l…