how engaging payers early transformed our clinical ... · indication prioritisation business case...

How engaging payers early transformed our clinical development and portfolio planning

A case study

Introduction

2

Erik Holzinger / PresenterBernd Muehlenweg / by Video

Erik Holzinger MBA is founder of groupH, the agile market insights firm informing key pre-launch business decisions facing pharmaceutical and biotech companies, including Commercial Opportunity Assessments, primary, secondary and early-stage Market Access, Disease Area models and TPP attribute analysis

Bernd Mühlenweg, PhD is CBO of Nanobiotix, the late-stage clinical company pioneering nanomedicine in oncology. He ensures the company’s sustainable growth by concluding strategic alliances with partners and until recently was responsible for market access and launch readiness

• The result is a non specific cellular destruction of the

primary tumor leading to increased local control

Lead indications: Soft Tissue Sarcoma and Head & Neck

Follow-on indications: liver, prostate and rectum cancer

Nanobiotix snapshot• Company founded in 2003, listed on Euronext in 2012

• Nanomedicine pioneer in oncology

• Developing first-in-class product for oncology that could

help millions of cancer patients

Lead technology NanoXray• The lead product, NBTXR3, has a universal, physical

mode of action: Increase energy absorption and dose

deposition within the tumor

• Once injected in the tumor, nanoparticles disperse within

the tumor and persist during the course of radiation

therapy

• When bombarded with ionizing radiation, the physical

properties of the nanoparticles lead to a massive energy

absorption / deposition

Nanobiotix and its lead product

Overview

5

We are firm believers that it is not enough to approve aproduct to make it used and accepted for the benefit of patients

Biotech companies have even more upsides of early market research

Sources: Linkedin, Focused Ultrasound Foundation, 123RF.com

7

Nanobiotix addressed the payer hurdle very early in the clinical development of its lead product

Project History

Additional Indication Overview

2009 2016201520142013201220112010 2017

Commercialisation Framework & Pricing

Business Plan Review

Opportunity Update Indication

Value Assessment + Opportunity

Update

High Level Opportunity Evaluation

Portfolio Management Tool

Early Payer Work

BROAD – 5 Indications – 6 countries Stakeholder landscape Reimbursement Frameworks Endpoints / evidence

Pivotal Payer Work

Indication PRIORITISATION Business Case different indications NPV + trial scenarios Detailed dTPP discussions with

payers Endpoint and evidence validation

Phase IIb endpoints QoL endpoints Forecast Update

“the early days” “getting the BIG and small things right”“preparing for the

Big Day”“…more refining…”

Launch

Phase I Phase IIb

Early Payer Work

Pivotal Payer Work

The Early Days2009 - 2012

8

What were the insights from early payer interactions?

• Initial payer perception positive … but not without further asks• ‘more than local endpoints’

• NanoXray is unique• Appropriate comparators to be identified?

• New codes will be needed

• Per-patient-pricing desirable but also possible?• National level payers versus pharmacists

Early Insights

Source: groupH research & analysis, Nanobiotix

Some of major development uncertainties could be reduced through the research, some new ‘homework’ and questions were added


HighLow

Hig

hCe

rtai

nty

Low

Impact

Per patient or per vial pricing?

Clarity on Reimbursement & Pricing Frameworks

Pre - Phase I

Payer evidence:Local vs. survival

Which Quality of Life + functional endpoints?

New Homework

Quadrant 4Initial payer

reaction

• Clear and solid business case based on feedback from KOLs and payers

• Focus on generation of early clinical evidence with hard endpoints. Prioritisation of additional indications for proof-of-concept

• First payer feedback providing perspectives for‘expectations’

• Support for licensing and partnering discussions(licensing agreement for Asia-Pacific) in Q3 2012and in support of IPO in Q4 2012

There were additional higher-level benefits for NanobiotixEarly Benefits

Getting the BIG and small Things Right2013 - 2015

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Pivotal Physician & Payer Research prior to Phase IIb trial


Detailed TPPs

Trial Scenarios NPV modelling

• 12 weeks• 6 countries• 20 Payers• 22 Doctors• Qual/Quant Research• 6 work streams

The pre-Phase II pivotal payer work allowed indication prioritisation and reality checking of proposed Phase II design


HighLow

Hig

hCe

rtai

nty

Low

Impact

Indication Sequence

Payer vs. doctor ‘vision’: Definitive RT across indications beyond the current STS development?

New Homework

Pre-Phase II/III

Quadrant 4Price RangeDetailed Clinical +

Competitive Environment

Pre-Phase I Homework around

Positioning and Trial Design

• Separation of clinical and payer value in early clinical development as the company understood that these can be different

• Clear perspective on clinical and payervalues which lead to a substantiatedbusiness case used for partneringdiscussions

This provided the basis for decisions on higher level strategic questions

Pivotal Payer Project Benefits (1)

• First complete alignment across the company regarding the registration study in Soft Tissue Sarcoma and expected outcomes as well as NBTXR3 positioning within Soft Tissue Sarcoma

• First amendment of the registration study to include different quality of life scales as suggested by payer feedback

• Identification of market entry barriers and missing scientific data within literature “to make the case”

• Initiation of numerous real world studies to closedata gaps identified during market research

… and actionable insights affecting the clinical study coupled with required “home work” to establish sustainable evidence

Pivotal Payer Project Actionable Insights

Talking Payer Language

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“The extent to which an intervention does more good than harm compared to one or more intervention alternatives for achieving the

desired results when provided under the usual circumstances of health care practice”

Adapted by patient, patient segment or for most patients

“The extent to which an intervention does more good than harm under ideal circumstances”

Averaged across a large patient population

Why do payers think differently?


PayersRelative Efficacy

Regulators / DoctorsEfficacy

Erik

Internationally, payers speak a common language around relative efficacy compared to the standard of care…

Source: groupH research & analysis

Payment by result

Healthcare System

QoL Premium

HTA

Patient Access Programs

Private/PublicDecentral

Public/StatutoryCentral



emerging

HEOR need

MethodRelative efficacy

Ranking / EFCost per QALY

thresholdvariousRelative efficacy

score

Relative efficacy/value elements

Access restrictions Tiers / Co-PayPrior Authorisation FormulariesFormularies

…despite working

within very different

healthcare systems

established established established

High

Medium

Low

Criteria

Budget impact

Formularies

increasing

National level payers• Health economics academics (e.g. head of health economics for a large

university research group)• Member HAS transparency commission in France• Member of G-BA arbitration committee or adviser to G-BA/IQWIG in G• Member of NHS Specialised Commissioning Group in UK

Are all payers the same?


Regional level payers• E.g. regional formulary pharmacists, NHS England pharmacists• Head of regional Drugs & Therapeutics Committee• Head of KV Prescription Committee in Germany

Local level payers• E.g. DTC chairs• Trust/hospital finance directors• Hospital chief pharmacists

Every project is different but for early strategic work,

national level ‘real’ payers who speak industry language

are easiest to work with

When to engage payers, Phase I, II or III?

“Informal” payer engagement

Reduce payer value uncertainty

Early partnership instead of a ‘hurdle’

Formal payer engagement+ Early Dialoguee.g. EMA parallel Scientific AdviceEUnetHTAMoCANational Scientific Advice

Year L-7 Year LYear L-1Year L-2Year L-3Year L-4Year L-5Year L-6 Year L + 1

Phase I Phase II Phase III

Phase III Data

Phase II Data

Phase I Data

Regulatory Submission

Regulatory Approval

Reimbursement

DossierSubmissionPre-clin

Pre-clinData

Phase IIIb

Payer value data

Phase IIb

Earlier engagement

Additional Evidence Programs

How to engage them? Data & topicsPhase I Phase IIPre-clin

Approach

Briefing pack: • short product TPP (concept only)• Indication overview including current SoC and

unmet needs

Topics:• First reaction• Reimbursement framework + evaluation process• Validation of concept and positioning• Possible comparators• Evidence requirements + endpoints

Pivotal/Follow-up Payer WorkBriefing pack: • More detailed TPP including clear payer value

elements and proposed evidence• Indication briefing pack – update + detail

Topics:• In-depth discussion of proposed evidence including:

efficacy, safety, l/t data, population relevance, HRU• Clinical benefits, economical benefits• If relevant: QoL endpoints, HEOR• Validation of rationale for each value element• Open and closed pricing• Comparators

Towards Phase III +

or

How to engage payers effectivelyA few comments from payers themselves …


What is the benefit of ‘early’ payer consultations and how early is ‘early’?

1 min1 min 1 min1 min 1 min

Mathias Flume is the Head of Business Unit Prescription Management at the Kassenärztliche Vereinigung Westfalen Lippe in DortmundHe is a frequent speaker and panelist at conferences on AMNOG and IQWiG, focusing on the understanding evaluation of patient benefit by GBA

David Cunningham, former payer from NHS England and medical oncologist as background. He is now working in Healthcare Strategy and Management

Which communication formats do payers prefer to work in?

Integrating Payer Findings

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• Transparent preparation of the research to make sure all stakeholders understand

Why do we do it? What do we want to achieve? That consequences may be implemented!Don’t take for granted everyone in the company understands despite claiming so!

• Intense utilization of agency to align internal stakeholdersand to present and explain meaning of findings

• Transparent discussion of payer findings as “real worldfeedback” across departments making sure that eachstakeholder understands the “convenient” and the“inconvenient” findings

• Joint decisions to implement consequent joint actions

Integrating convenient and inconvenient payer findings into company operations by engaging internal stakeholders

Lessons Learned & Recommendations

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• Understanding the case from both, clinical and payer perspective including the broad data landscape

• Engaging payers early for ‘red flags’ and expectation setting• Informal pivotal payer value discussions optimise the

approach and avoid nasty surprises which cannotbe corrected later

• Payers can change the vision for a product,it is not just about pricing

• Early implementation of time-consuming correctiveactions to decrease later pressure

• Each case is different and the focus mustindividually be tailored towards the product

Early KOL and payer market research: Lessons Learned & Recommendations


Thank You!!

28

Appendix (currently not part of 25 min. presentation)

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How to engage payers effectivelyA few comments from payers themselves …


What is ‘payer-evidence’ and why is it different from regulatory evidence?

1 min1 min 1 min1 min 1 min

Mathias Flume is the Head of Business Unit Prescription Management at the Kassenärztliche Vereinigung Westfalen Lippe in DortmundHe is a frequent speaker and panelist at conferences on AMNOG and IQWiG, focusing on the understanding evaluation of patient benefit by GBA

• “Whether NBTXR3 is a radio-sensitizer or not is likely to be debated amongst payers. However with clear demonstration of therapeutic benefits, the outcome of this debate will have little influence on pricing and reimbursement” – Nicolas Touchot, groupH

• “For me there are still questions on your proposed trials. Some of these questions you may be able to answer with education and by explaining the rationale, I cannot say for sure.” – Italian Payer

• “In a value based pricing environment, you cannot have a difference in price per tumorthat is not justified. This would really complicate things and create high hurdles to reimbursement.” – UK Payer

• “We are used to different price per patient, but not of that level. I don’t think this would be possible. The discussions between the insurances and the hospitals would be very complex.” – US Payer

Payer feedback to the updated TPP


Preparation, topics and structure of a 3h EU Payer Online Ad-board as used for Nanobiotix


Discuss and understand the likely reimbursement process for a product such as NanoXRay (DRG, Specific reimbursement, others,…)

Discuss and understand the likely HTA process for a product such as NanoXRayincluding supporting evidence

Understand potential Market Access hurdles and identify approaches to overcome those hurdles

Obtain reactions to the development plan and to the proposed evidence for NanoXray

Discuss pricing framework options – Discuss pro’s and con’s of various approaches to resolve volume discrepancy across patients and cancer types

Evaluate potential price range(s) for the product

Payer Value Uncertainty*

Payer online ad-board

* including: efficacy, safety, l/t data, population relevance, HRU

Client Commercial

Uncertainties

Formal payer dialogue is becoming more structured

• Emerging US HTA Value Frameworks

• Early Dialogue Processes& Vehicles in Europe

• The EMA parallel Scientific Advice

• The EunetHTA multi HTA advice

• MoCA (“Mechanism of Coordinated Access to Orphan Drugs”)

• We know that historic oncology pricing does not always correlate with the ASCO value framework – as the ASCO framework is fine-tuned we expect this to change

Future payer research considerations


Erik

Typical Payer Interviewee Profiles

• Medical directors and members of the formulary committee of top ten national health plans, integrated delivery networks, large regional plans, and Medicaid managed care

• Heads of contracting / Medical Directors Large Sick Funds

• Head Pharmacists and Heads of Pharmacy Committee, University hospital

• Members of GBA and GBA

• Former HAS Transparency Committee members

• Members of pricing committee (CEPS)• Hospital pharmacists, heads of COMEDIMS

• Members of AIFA Advanced Therapies

• Members of AIFA CPR (Comitato Prezzi e Rimborso)

• Members Regional Health Authorities

• Hospital Pharmacists, Large Regional Oncology Center

• Members of regional HTA Committees

• Members of NHS Finance

• Medical and formulary directors NHS trusts

• Members of Specialized Commissioning

groups

• Members of NICE Evidence Review Groups

• Former member of the Catalonia Health Technology Assessment Group

• Current member of the InterterritorialCouncil

• Former member of the Ministry of Health (involved in pricing negotiations for novel products)

• Member of Regional Health Department (Madrid)

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