Skip to content
  • About
  • Contact
  • Contribute
  • Book
  • Careers
  • Podcast
  • Recommended
  • Speaking
  • All
  • Physician
  • Practice
  • Policy
  • Finance
  • Conditions
  • .edu
  • Patient
  • Meds
  • Tech
  • Social
  • Video
    • All
    • Physician
    • Practice
    • Policy
    • Finance
    • Conditions
    • .edu
    • Patient
    • Meds
    • Tech
    • Social
    • Video
    • About
    • Contact
    • Contribute
    • Book
    • Careers
    • Podcast
    • Recommended
    • Speaking

Dementia patients want effective drugs. How will the FDA respond?

Ron Louie, MD
Meds
May 16, 2018
Share
Tweet
Share

Dementia patients want effective drugs. Five years ago, the Food and Drug Administration (FDA) proposed changes to speed drug approvals for Alzheimer’s disease (AD). No new drugs have been approved. This year, a new FDA draft guidance discusses considering biomarker data and changing cognitive evaluations for accelerated approvals. Would that help make effective drugs available, or are we lowering our expectations?

Numerous dementia agents have failed current improvement standards in trials, which require positive changes in both cognitive and functional measures. One hypothesis about the failures is that symptomatic patients are poorly salvageable, so a better target might be earlier stages of dementia. The new guidance suggests a specific staging system for early AD. The earliest stage subjects would have measurable “Alzheimer’s biomarkers” but no measurable cognitive or functional symptoms.

Since such subjects don’t have measurable symptoms to impact, drugs demonstrating biomarker improvement alone might be eligible for accelerated approval, with a requirement for studies “to confirm the predicted clinical benefit.”

Accelerated approval isn’t necessary to conduct such efficacy studies; it almost would seem that drug payers would be helping to fund them.

Bapineuzumab, an amyloid therapy, changed neuroimaging and spinal fluid biomarkers in symptomatic AD patients, but failed to meet improvement criteria for approval. Adverse effects such as hippocampal atrophy are still being interpreted . Solanezumab, another amyloid agent, had an effect on biomarkers but also failed. The guidance seems to suggest that these agents could be considered for accelerated approval in asymptomatic persons if further “persuasive” results were presented.

Interestingly, the document states that currently “there is no consensus as to particular biomarkers that would be appropriate to support clinical findings in trials in early AD,” and that “the certainty of their [the subjects’ ] future clinical course” must still be established.

Interpreting those statements, the FDA is not yet satisfied with the current documentation of progression in early AD. If progression is not well defined, how does one know if a drug is effective in preventing Alzheimer’s disease?

The FDA document discusses why the current dual criteria may not be appropriate. The guidance encourages improving current cognitive measures in a “meaningful” way. This begs the question of whether the dual measures are protecting symptomatic patients from ineffective drugs or keeping them from drugs that might be effective.

In this context, it is interesting to look at Avastin’s accelerated approval (2009) for another intractable brain disease, the malignant tumor progressive glioblastoma multiforme (GBM). Avastin’s first FDA label stated: “Effectiveness based on improvement in objective response rate. No data available demonstrating improvement in disease-related symptoms or survival with Avastin” . Response rate included neuroimaging, notoriously problematic in GBM . (Alzheimer biomarkers include neuroimaging).

Only recently, combination chemotherapy trials that included Avastin showed several months benefit in progression free survival (PFS), with no change in overall survival; that evidently helped full approval . Years of earlier studies were not convincing. It is still not recommended for frontline therapy, and is not considered curative.

Some consider PFS a surrogate measure. There were adverse events associated with Avastin and impacts on quality of life in the study. A dilemma for us oncologists prescribing drugs like Avastin is gauging whether they really help patients or just “prolong dying.” A similar dilemma would confront dementia physicians if new agents are approved with FDA labels similar to that above, which seems possible from the draft guidance.

What one wants from FDA approval is a drug that has a reasonable chance of a discernible good effect, with tolerable safety. Ironically, the FDA allows television marketing of “brain supplements,” readily available over the counter, even dog food for canine cognitive issues. Of course, the agency has different standards for those categories, mainly safety, not efficacy.

The FDA seems to be taking a directive leadership role here, throwing down some challenges. Perhaps the new recommendations will spur development that will provide therapies for all stages of AD, so that one day we will have something that “really works,” even if we may have to lower our expectations for now.

ADVERTISEMENT

Ron Louie is a pediatric oncologist.

Image credit: Shutterstock.com

Prev

Blockchain technology can dramatically transform health care delivery

May 16, 2018 Kevin 6
…
Next

Nurses made this doctor who she is today

May 16, 2018 Kevin 9
…

Tagged as: Neurology

Post navigation

< Previous Post
Blockchain technology can dramatically transform health care delivery
Next Post >
Nurses made this doctor who she is today

ADVERTISEMENT

More by Ron Louie, MD

  • Will Alzheimer’s disease researchers miss seeing the forest from the trees?

    Ron Louie, MD
  • Do substituted decisions break the Golden Rule?

    Ron Louie, MD
  • Interpreting 2 recent studies involving Alzheimer disease

    Ron Louie, MD

Related Posts

  • Are patients using social media to attack physicians?

    David R. Stukus, MD
  • You are abandoning your patients if you are not active on social media

    Pat Rich
  • The FDA was wrong about Aduhelm

    M. Bennet Broner, PhD
  • A love letter to patients

    Marcie Costello
  • Patients are not passengers

    Christopher Noll, RN, MSN
  • Expensive Medicare patients aren’t who you think

    Peter Ubel, MD

More in Meds

  • Why kratom addiction is the next public health crisis

    Muhamad Aly Rifai, MD
  • FDA delays could end vital treatment for rare disease patients

    GJ van Londen, MD
  • Pharmacists are key to expanding Medicaid access to digital therapeutics

    Amanda Matter
  • How medicine repurposing enables value-based pain management and insomnia therapy

    Olumuyiwa Bamgbade, MD
  • Forced voicemail and diagnosis codes are endangering patient access to medications

    Arthur Lazarus, MD, MBA
  • From stigma to science: Rethinking the U.S. drug scheduling system

    Artin Asadipooya
  • Most Popular

  • Past Week

    • COVID-19 was real: a doctor’s frontline account

      Randall S. Fong, MD | Conditions
    • Why primary care doctors are drowning in debt despite saving lives

      John Wei, MD | Physician
    • Aging in place: Why home care must replace nursing homes

      Gene Uzawa Dorio, MD | Physician
    • How federal actions threaten vaccine policy and trust

      American College of Physicians | Conditions
    • When the clinic becomes the battlefield: Defending rural health care in the age of AI-driven attacks

      Holland Haynie, MD | Physician
    • mRNA post vaccination syndrome: Is it real?

      Harry Oken, MD | Conditions
  • Past 6 Months

    • The shocking risk every smart student faces when applying to medical school

      Curtis G. Graham, MD | Physician
    • COVID-19 was real: a doctor’s frontline account

      Randall S. Fong, MD | Conditions
    • Why so many doctors secretly feel like imposters

      Ryan Nadelson, MD | Physician
    • Confessions of a lipidologist in recovery: the infection we’ve ignored for 40 years

      Larry Kaskel, MD | Conditions
    • A physician employment agreement term that often tricks physicians

      Dennis Hursh, Esq | Finance
    • Why taxing remittances harms families and global health care

      Dalia Saha, MD | Finance
  • Recent Posts

    • Putting food allergy safety on the menu [PODCAST]

      The Podcast by KevinMD | Podcast
    • Why transgender health care needs urgent reform and inclusive practices

      Angela Rodriguez, MD | Conditions
    • Why “the best physicians” risk burnout and isolation

      Scott Abramson, MD | Physician
    • Why the Sean Combs trial is a wake-up call for HIV prevention

      Catherine Diamond, MD | Conditions
    • Why real medicine is more than quick labels

      Arthur Lazarus, MD, MBA | Physician
    • New surge in misleading ads about diabetes on social media poses a serious health risk

      Laura Syron | Conditions

Subscribe to KevinMD and never miss a story!

Get free updates delivered free to your inbox.


Find jobs at
Careers by KevinMD.com

Search thousands of physician, PA, NP, and CRNA jobs now.

Learn more

View 1 Comments >

Founded in 2004 by Kevin Pho, MD, KevinMD.com is the web’s leading platform where physicians, advanced practitioners, nurses, medical students, and patients share their insight and tell their stories.

Social

  • Like on Facebook
  • Follow on Twitter
  • Connect on Linkedin
  • Subscribe on Youtube
  • Instagram

ADVERTISEMENT

ADVERTISEMENT

  • Most Popular

  • Past Week

    • COVID-19 was real: a doctor’s frontline account

      Randall S. Fong, MD | Conditions
    • Why primary care doctors are drowning in debt despite saving lives

      John Wei, MD | Physician
    • Aging in place: Why home care must replace nursing homes

      Gene Uzawa Dorio, MD | Physician
    • How federal actions threaten vaccine policy and trust

      American College of Physicians | Conditions
    • When the clinic becomes the battlefield: Defending rural health care in the age of AI-driven attacks

      Holland Haynie, MD | Physician
    • mRNA post vaccination syndrome: Is it real?

      Harry Oken, MD | Conditions
  • Past 6 Months

    • The shocking risk every smart student faces when applying to medical school

      Curtis G. Graham, MD | Physician
    • COVID-19 was real: a doctor’s frontline account

      Randall S. Fong, MD | Conditions
    • Why so many doctors secretly feel like imposters

      Ryan Nadelson, MD | Physician
    • Confessions of a lipidologist in recovery: the infection we’ve ignored for 40 years

      Larry Kaskel, MD | Conditions
    • A physician employment agreement term that often tricks physicians

      Dennis Hursh, Esq | Finance
    • Why taxing remittances harms families and global health care

      Dalia Saha, MD | Finance
  • Recent Posts

    • Putting food allergy safety on the menu [PODCAST]

      The Podcast by KevinMD | Podcast
    • Why transgender health care needs urgent reform and inclusive practices

      Angela Rodriguez, MD | Conditions
    • Why “the best physicians” risk burnout and isolation

      Scott Abramson, MD | Physician
    • Why the Sean Combs trial is a wake-up call for HIV prevention

      Catherine Diamond, MD | Conditions
    • Why real medicine is more than quick labels

      Arthur Lazarus, MD, MBA | Physician
    • New surge in misleading ads about diabetes on social media poses a serious health risk

      Laura Syron | Conditions

MedPage Today Professional

An Everyday Health Property Medpage Today
  • Terms of Use | Disclaimer
  • Privacy Policy
  • DMCA Policy
All Content © KevinMD, LLC
Site by Outthink Group

Dementia patients want effective drugs. How will the FDA respond?
1 comments

Comments are moderated before they are published. Please read the comment policy.

Loading Comments...