Working Group: Behavioral and Psychiatric Symptoms in · PDF fileBEHAVIORAL AND PSYCHIATRIC SYMPTOMS IN DEMENTIA 2/21/17, Washington DC Co-chairs Larry Ereshefsky David Miller

CONFIDENTIAL 2014 PAREXEL INTERNATIONAL CORP.

WORKING GROUP:

BEHAVIORAL AND

PSYCHIATRIC SYMPTOMS

IN DEMENTIA

2/21/17, Washington DC

Co-chairs

Larry Ereshefsky

David Miller

Luca Pani

2

BPSD WORKING GROUP PROPOSAL ABSTRACT

Objectives: This working group is being convened to focus on the methodological challenges

facing the development of treatments for the Behavioral and Psychiatric Symptoms of Dementia

(BPSD). This group was in part stimulated by the EMA Alzheimers Disease Workshop.

Convey critical importance of treating BPSD, i.e., Apathy as a means to improve patient QOL,

extend patients stay in their home environment; improve overall

Review of lessons learned from ongoing and prior clinical trials for BPSD.

Proposing innovative trials designs and regulatory acceptance;

Managing intrinsic variability of symptoms;

Evolving AD diagnostic and biomarker approaches

Staging of illness and impact on symptoms, response, study design;

Regulatory perspectives

Workshop Deliverables and Action items/Steps to move the field forward

Extend collaboration with ISTAART PIA; review activities of PIA and FRS for AAIC;

Finalize program for 2017 Autumn meeting in Paris

Consider establishing WG team to:

look at challenges and lessons learned from past/current clin trials to treat BPSD; create

review article, road map, and/or report for presentation at ISCTM or other meetings

http://www.ema.europa.eu/ema/index.jsp?curl=pages/news_and_events/events/2014/04/event_detail_000932.jsp&mid=WC0b01ac058004d5c3https://isctm.org/meeting/2017-autumn-conference/

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AGENDA FOR WORKING GROUP ON BPSD

Introductions/Dinner

1. Collaboration between ISTAART, NPS PIA and ISCTM BPSD WG

Co-Chairs Krista Lanctt, Joanne Bell PIA

2. Discussion with drug sponsors providing insights Part I:

Agitation/Psychosis/BPSD

3. Discussion with drug sponsors providing insights Part II: Apathy

4. To assess the feasibility/desirability for ISCTM to support a consensus

group.

Identify opportunities and pathways for collaboration with the Biomarkers Consortium even

though the FNIH Endpoints Working Group was not funded

5. Neurocircuitry/Biomarker strategies

6. Action Items/Deliverables:

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RX OF EXISTING SYMPTOMS OR DELAYS/PREVENTION OF LIKELY TO OCCUR SYMPTOMS OF NPS

5

AGENDA

Collaboration between ISTAART, NPS PIA and ISCTM

BPSD WG

Co-Chairs Krista Lanctt, Joanne Bell PIA

Report on joint NPS PIA and BPSD ISCTM activities including featured

research symposium submitted February 1st to AAIC

Other activities related to ongoing collaborations, including ISCTM

involvement in the PIA Day and ISTAART involvement in Paris ISCTM

meeting

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AAIC FRS SUBMITTED, LONDON, JULY 16-20, 2017

ADDRESSING THE CHALLENGES IN TREATING APATHY

ASSOCIATED WITH ALZHEIMER'S DISEASE

Larry Ereshefsky and Krista

Lanctot, co-chairs

Drug Development and Treatment

of Apathy, David Miller

Apathy Neurocircuitry, Brain

Imaging Findings and

Implications, David Sultzer

Examining the Neurocircuitry of

Apathy and Markers of

Neurodegeneration in Early

Alzheimers Disease, Gad Marshall

Pathways Forward in Treating

Apathy: Regulatory Perspectives,

Karl Broich

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Session 4: Addressing challenges in the drug development of

behavioral and psychological symptoms in dementia

The constellation of symptoms/syndromes comprising BPSD (NPS) present

a challenge at all levels of health care, from unmet patient and caregiver

needs, to drug discovery, to clinical trials, as well as to regulatory pathways.

A review of the lessons learned from recent efforts to develop drug

treatments for Agitation or Psychosis in neurodegenerative disorders will be

applied to enable methodological discussions on the development of

treatments for Apathy in Alzheimers Disease (AD). We will explore how

Apathy symptoms and potential biomarkers evolve across the spectrum

from Mild Brain Impairment (MBI) to Mild Cognitive Impairment (MCI) to AD.

What are accepted diagnostic criteria for Apathy in AD and will disease

progression affect treatment targets and assessment tools? How should

pseudo-specificity be addressed in identifying and assessing apathy?

Differentiation from depression and relationship with changes in cognition

will be discussed. What are the challenges of conducting translational and

proof of concept work in patients with Apathy in MBI/MCI? The application of

neurocircuitry strategies and other biomarker approaches in early drug

development could de-risk POC. Regulatory considerations of approaches

and methodologies to improve the likelihood of meaningful signal detection

and acceptable registration trials will be discussed.

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BEHAVIORAL

AND

PSYCHIATRIC

SYMPTOMS IN

DEMENTIA

(BPSD): A

WAY

FORWARD?

ISCTM

AUTUMN

MEETING, LE

MERIDIEN,

PARIS,

SEPTEMBER

2ND 2017

0830 Background, brief overview of sessions purpose Larry Ereshefsky

Luca Pani

0840 Current drug development for the treatment of AgitationAddress Strengths/weaknesses and trial design considerations of current studies

-- add influence of non drug interventions??

Clive Ballard, Kings College

9:10 Lessons Learned Part II Agitation: Paul Rosenberg,

Johns Hopkins

0940 Discussant, Panel-Audience Discussion: Jill Rasmussen/

Joanne Bell,

1000 Break

1015 Why focus on apathy? David Miller, Bracket

1045 Neuro-circuitry and implications for drug development ; study designs for treatment of

Apathy

Krista Lanctot,

Sunnybrook Health

Sciences Centre,

Toronto

1115 Similarities/differences in the symptoms of apathy in Psychiatry (schizophrenia and

depresson), and in neurodegenerative disorders (Alzheimers and Parkinsons Disease)

Pharma discussant on neurocircuitry strategies: Update on FNIH thinking to address

Apathy/Reward across various diagnostic categories (i.e., assessment tools,

differences in symptom presentation, biological/biomarker implications)

Larry Ereshefsky,

Follow the Molecule

Stephane Pollentier,

Boehringer Ingelheim

(tent)

1200 Regulatory View point(s) EMA confirmedUS view point (necessary?)

Identify a regulatory consultant to provide

Valentina Mantua

and Karl Broich,

EMA

Invite Alzheimers

Association, Maria

Carrillo, to comment,

lack funding to

support; would she

be attending ECNP

(to be asked by PIA)

1230-

1 PM

Discussant, Panel-Audience discussionAdjourn

Larry Ereshefsky/

Luca Pani plus

presenters

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STRATEGIES FOR FDA ENGAGEMENT AND

COMMENTARY IN PARIS SYMPOSIUM

SC/EC suggested a few strategies:

Pre-recorded comments from a key FDA Regulator on the path forward for Apathy

Question/Answer interview, also pre-recorded with symposium leader, incorporating

content from the presentations (will require advance input from presenters)

Less likely, more complex, live videoconferencing. Session on Saturday, runs

afternoon to evening EST

Available by phone to provide comments or Q/A

Would also ask Valentina, Luca, and/or Karl to highlight in their comments that describe

areas of communication and engagement between EMA and FDA

Drug development for Behavioral

Symptoms of Dementia:

Methodological Challenges and

Potential Solutions

CEDRIC OGORMAN MD

THE BPSD WORKING GROUP

WASHINGTON D.C.

21 FEBRUARY 2017

Background: The Need for BPSD

medicines

No approved treatments for BPSD

Lack of required studies to support efficacy of antipsychotics for BPSD or psychosis of dementia

Many negative and some positive registrational studies what can we learn?

Non-approved use of existing antipsychotics (20-50%1) and other sedative medications have serious safety concerns (increased mortality, CVAs, drowsiness, falls, increased morbidity)

Class labelling for atypical antipsychotics (weight, type 2 diabetes, metabolic syndrome and hyperlipidemia)

BPSD are highly prevalent and a leading cause of institutionalization

Clinicians and regulators recognize the need for newer safer and effective treatments for BPSD

1. Feng, Z. et al. (2009) Use of physical restraints and antipsychotic

medications in nursing homes. Int J Geriatr Psychiatry 24: 11101118.

Challenges in the development of

medicines for BPSD

Clinical Trial Design Considerations

Patient Population Who? What? Where? (At home vs. In assisted-living; nursing homes etc)

Diagnosis

Symptom Eligibility: Duration, Severity and Frequency

Duration of treatment

Patient-reported outcomes

Role of the caregiver

Rating, Raters & Rater Training

Understanding how pl