When novelty is not enough:Assuring adoption, access, as well as

approval within the clinical development process

Michael F. Murphy M.D. Ph.D.Chief Medical and Scientific Officer, Worldwide Clinical TrialsResearch and Development Editor, American Health and Drug Benefits™

Teaching Faculty, Center for Experimental Pharmacology and TherapeuticsHarvard-MIT Division of Health Sciences and Technology

Disclosures

Acadia Coronis GB Sciences Neumentum RMJH Rx

AgeneBio Cortexyme Gideon Richter Neuralstem Roche

Amygdala Cristcot Global Blood Therapeutics NeuroRx R-Pharm

Aptinyx Curadim Immunova Neurotrope Rubius

ARC Cytogel Incys Novus Sanofi Genzyme

Argenx Diurnal Isothrive Orchard Sinopia

ArQule Dynacure Medivir PanX Spruce

AudioCure Eisai Momenta Philip Morris Int. Suven

Aurin EMS Navinta Praxis X4

BioXcel Frequency Therapeutics NeoTrope Rhythm

Michael F. Murphy M.D. Ph.D.Chief Medical and Scientific Officer, Worldwide Clinical Trials

Research and Development Editor, American Health and Drug Benefits™Teaching Faculty, Center for Experimental Pharmacology and Therapeutics

Harvard-MIT Division of Health Sciences and Technology

“I have time to ask three questions– how’s your gallbladder, how’s your teeth, and do you have

good outpatient pharmacy coverage”

Interventional CardiologistBirmingham, AL

Prior to PCI

We Will Discuss

• The “other” stakeholders

• Starting at the End

• Looking beyond the obvious

• Competing on value, not novelty

The “Other Stakeholders”

Care Providers

Academia

Physicians

Labs

Products & Services

Intermediaries

Consumers

Governments

Devices

StatesDisease Management

Insurers

Global Regulation Regional Variation

Medicare -Medicaid

Basic Researchers

Employers

Insured

Seniors

Women

Children

Unions

Uninsured

Nurses

Neither orderly nor rational, multiple stakeholders impact R&D with

conflicting data needs

Financial Markets

Assisted Living

Nursing Homes

Med Tech

Bio TechPatients

Pharma

CMS, State Medicaid

Start with the End in Mind

“CMS coverage policies for Biologics: defining a Lagrangian point for cost, quality, and access”

“Capnography in procedural anesthesia: at the edge of a “perfect storm”

“Relieving nasal symptoms: uncommon excellence in a common clinical condition”

“Case Study: Insu-Nectin (NV 1008) for Type 2 Diabetes”

“Pharmaceutical R&D Strategy and the Transition to Personalized Healthcare Planning”

“Pharmacogenomics and Drug Development: A Stakeholder Perspective”

“Post-Approval Development Options in COPD A Case Study in Value-Based Healthcare Systems”

Michael F. Murphy M.D., Ph.D.Research & Development Editor

“The Metabolic Syndrome and Atypical Antipsychotic Medications: Risk Factors, Surveillance Methods, and Healthcare Implications”

“Medical Claims Data Can Inform Coverage Decisions inManaged Care Health Plans” - Angina in Patients with CoronaryArtery Disease in a US Managed Care Setting

David B. Nash M.D., MBAEditor-In Chief, Dean Jefferson School

of Population Health“Rarity, Disease Heterogeneity, and A Pathwayfor Estimating Economic Burden

Risk stratificationPersonalized Medicine

Orphan Disease Indications

Raises questions about validity of drug formularies and reimbursement mechanisms to control access to

therapeutics

Can this inform a development program?

Essential Component of Overall Innovation Value

Assuring adoption, payer coverage, and premium pricing

Intellectual Property Position

Cost of Goods Advantage

Improved Features &

BenefitsQuality

Innovation Value

Ability to Leverage Core Competencies

Market Attractiveness

Fit Within Company Strategic Initiatives

Evidence-based Value

Clinical Impact

Economic Impact

Improved patient outcomes

Reduces downstream

costs

Result

?

?

HowImpact

Data during development creates a “value” proposition to inform technology investment decisions

Confidential - Used with Permission, Boston Healthcare AssociatesUsed with permission of Boston Healthcare Associates, Inc.

What if the Indication was “Fatigue”?

Different Prisms, Different Data

“What don’t they want?”

“Current stumbling blocks?”

“What they are willing to consider?”

“What’s promising given current perspectives?”

“How diverse are data needs?”

• Actuary• Employers• Epidemiology Research• Health Information Technology• Health Outcomes Research• Managed Care & Government Affairs• Managed Markets• Patient Advocacy• Pharmacy Benefit Design• Policy & Public Health• Reimbursement Policy• Research & Development• Specialty Pharmacy

Payers, Purchasers, Policymakers

• What they don’t want?• Paying for treatment requiring evidence that doesn’t exist

• What do they regard as stumbling blocks?• “Big enough to care about, but small enough to do something about?”• “Will it impact overall healthcare resource utilization?”• “Any guidelines?”• “Is this a lifestyle-modifiable condition?”• “Will this prompt disease-mongering? – it’s been done before!”

• What are they willing to consider?• Controlled and observational studies• Outcomes (direct, indirect, HRQOL, productivity)• Universally--- “bring me in prior to approval!”

Multiple Sclerosis – “Limiting Access if Value Uncertain”

Diverse Policies

Specialist Rx Only

Prior Authorization (+Re-authorization)

Tier Placement (~ 60%)

Require affirming benefit before and after therapy (~40%)

ADHD – “The Better the Data the Less the Management”

Strattera will face low reimbursement from HMOs. Parma Business Week

2003 JUN 9 - (NewsRx.com & NewsRx.net) --Decision Resources finds that Eli Lilly's Strattera

will face low or nonexistent reimbursementfrom HMO pharmacy directors…

“Out of pocket expenses range from $40-$230/ month across a

range of possible medications…and can substitute a generic without

physician permission”

PA Pharmacist

High Interest

Fatigue impact on cost drivers uncertain (Reimer et al, 2007; Wu et al, 2007;

Leibson et al, 2001)

“Interaction effects” (Page et al,2016)

Many Tools Control Utilization (Fail-First strategy, Preferred List, Co-insurance,

Co-pay)

Alzheimer’s Disease – “Looking Beyond the Patient”

Opportunities

Mild cognitive impairment(Zhu et al, 2013)

Informal care (Jönsson et al, 2006;Deb et al, 2017)

Depression, resilience, distress in caregivers (Lavretsky et al, 2010; Abreu

et al, 2018)

Schizophrenia – “Episodes of Care”

“Off the radar” for Some Stakeholders, Many Questions by Others

Fatigue entwined with Cognitive Impairment, Reduced Physical Activity?

Contribution to metabolic syndrome (CV outcomes)?

Poor compliance (institutionalization)?

Episodes of care (utilization)?

Depression – “Interest, but not where expected”

High Interest

Commercial PlansNon-Psychiatric Utilization (minor

somatic complaints including fatigue; Katon et al, 2001; Greenberg et al,

2015)

EmployersAbsenteeism, Presenteeism

(Druss et al, 2000; Cocker et al, 2014; Evans-Lacko and Knapp, 2016)

A Portfolio of Initiatives

The Rise of RWE

Accessible Cost Drivers in Development

No (minimal) Additional Expenditures

• Using Micro-environments (IDN)• The "big five in the EU“• Within study claims analysis• Piggybacking• Compendia

Additional Expense

• Longitudinal cohort, screen failure patients• Research Center (direct-to-patient call Center)

• If it’s after filing, it’s too late• Breakthrough?• “Novelty makes me nervous”• Patients in deep end of the swimming pool?• Practice topology as a prognostic factor?• Outcomes, not just measures?• Complementarity?• Budget impact vs cost effectiveness?• Piggy-back or Observational?• A publication package (adoption; access)

Systems/Provider Perspective: What are we Currently Doing and How is it

Working?

“Requires an alternative definition of translational research, demonstrating the value of an

intervention in the context of it’s novelty.”

In answer to the question