Ophthalmology Market Access by Dr Steven Bradshaw

©2015 Market Access Solutions Ltd. All rights reserved.

Market Access Solutions, Ltd Market Access Strategies for the Global Healthcare Environment

Therapeutic landscape in posterior segment disease: opportunities for patients, clinicians and for industry

Presented at the 15th EURETINA Congress NICE; 17th September 2015: #FP-7265

Steven Bradshaw BSc (Hons), MB BChir, MRCOphthEuropean Director, Market Access Solutions


Disclosure

Disclosure

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Market Access Solutions (Market Access Solutions Ltd and Market Access Solutions LLC) receive fees from industry for consulting on new and existing medicines

We did not receive any sponsorship to attend or present at EURETINA We will not be endorsing any particular product


1. Bringing a new eye therapy to market2. White space assessment in retinal disease• Objectives and methods• Findings• Considerations for clinical development in dry AMD

4. Conclusions and recommendations

3

Overview

Report Content


Once upon a time … efficacy and safety used to be enough

Background

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... provided that pharmaceutical products were safe and effective, doctors could prescribe them, patients could get their prescriptions filled, and payers would reimburse the costs


Now a number of challenges exist … payers need to balance healthcare demands with budgetary constraints

Background

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To optimize market access, pharma companies also need to demonstrate the value of the product during national and regional pricing and reimbursement negotiations … the requirements of payers are different to those of regulators

Phase 1 Phase 2 Phase 3

Clinical Development

MA P&R Launch

Commercialisation

Quality

Safety

Efficacy

Payer value = Market access

To achieve market authorisation/regulatory approval, pharma companies need to demonstrate that a product is safe, effective and meets quality standards

4th hurdle

The difference between market access and marketing is that market access requires evidence that payers value ...


What payers need to know … and what they tend not to consider

Background

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Is the product needed? (unmet clinical need) Does it work? (clinical efficacy) How well does it work? (clinical effectiveness) Can we control its use? (patient population) Is it worth it? (cost effectiveness) Can we afford it? (budget impact)

Tolerability Mechanism of action Pharmacokinetics Societal costs Route of administration Convenience for patients Indirect costs

Usually not factored in payer decision makingUsual factors in payer decision making




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Overview

Report Content


Assessing opportunities for new retinal therapies was the ultimate aim of this research

Objectives and Methods

Overarching goal Understand access opportunities for new entrants in posterior segment disorders

Key focus areas of the assessment

Understand the preceding and current/future clinical and market perspectives Identify the remaining unmet needs in each indication Outline the value drivers for access for future entrants Review HTA recommendations for each publically available evaluation Key insights for clinical trial design and launch in multiple indications and how

future agents can expect to achieve access and price

Indications Wet AMD, dry AMD, DME, non-infectious posterior uveitis and vitreomacular traction

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©2015 Market Access Solutions Ltd. All rights reserved. 9

Secondary research and qualitative interviews with 15 payers, decision makers and key opinion leaders across three major markets in Europe, plus Canada and Japan

Objectives and Methods

JapanFrance

Germany

United Kingdom

Market in scope

Canada




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Overview

Report Content


Characteristic Wet AMD Dry AMD DME Non-infectious posterior uveitis

Vitreomacular traction

Prevalence 170 per 10,000 and increasing

380+ per 10,000 and increasing

Average of 7% of diabetics affected 38 per 100,000 22.5 per 100 000

Disease burden A leading cause of blindness

Minor progressive symptoms

Major cause of visual impairment

Debilitating in acute phase

Symptoms are mild and develop slowly

Economic burden / Therapy costs

High cost anti-VEGF drugs

No reimbursed treatment

High cost anti-VEGF drugs

Low cost drugs available

One off surgical costs

Unmet needBurdensome

disease but good treatments

No current therapies

Burdensome disease but good

treatmentsTreatments

availableTreatments

available

Competitive environment (pipeline)

Fovista and biosimilars

Lampalizumab and other products in

pipelineSeveral licensed

products launchedFew treatments in

pipelineFew treatments in

pipeline

Payer management PAS required for cost-effectiveness

No cost control but no available budget

PAS required for recommendation

Off-label products available

PAS maybe required for

recommendation

HTA challenges Current therapies required PAS

Unknown environment

Population restrictions likely

Low incentive to review

Payers more aware since Jetrea

Overall opportunity of entering therapy area

MEDIUM: Competitive and

highly managed with effective SoC

HIGH: First to market product could have significant impact

MEDIUM: High population but

treatments available

LOW: Small population with off-

label treatments used

LOW: Small population and increased Payer

awareness

Opportunity Assessment

Opportunity in posterior segment disorders based on multicriteria assessment of perceived clinical burden, unmet need, market dynamics and payer environment

PAS = patient access scheme; SoC = standard of care



The market landscape is expected to transform should one or more pipeline developments prove successful

Lampalizumab is expected to be the first drug to enter the dry AMD market• 20.4% reduction in geographic

atrophy progression from month 6 through month 18 in its phase II study

• phase III is ongoing and includes patients that are positive for the complement factor I biomarker; the primary endpoint is reduction in the rate of geographic atrophy progression

Cell therapies are still in early phase of development, showing promising results and indicate a high price tag

Therapies being developed for dry AMD - Clinicatrials.gov Dec ’14

The key challenge for any product to reach patients, is to demonstrate clinical and economic outcomes that resonate with payers ...




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Overview

Report Content


1 2 3 4 5

Payers (n=4) KOLs (n=10)

Clinical Development Considerations

Perceptions vary between payers and KOLs, with the former suggesting change in BCVA and the latter change in GA as the optimal primary efficacy measure in dry AMD

Change in Best Corrected Visual Acuity (BCVA)

Functional

Change in central visual fields

Near acuity/ Reading speed

Contrast sensitivity

Visual Function Questionnaire (VFQ-25)

AMSLER testing

Change in drusen size/ area

AnatomicalHyper/ hypo-pigmentation

Central retinal thickness

Rate of change in the area of geographical atrophy (GA)

← Value →

Notes on interpretation: Interviewees were asked to score the value of each endpoint on a scale of 1 (low) to 5 (high). Scores were averaged for payers (n=4) and KOLs (n=10).

Low High

Perceptions of dry AMD endpoints

1 2 3 4 5


=Payer-preferred =KOL-preferred


1 2 3 4 5



Other anatomical endpoints with no clear relevance to patient outcomes are scored lower in value, especially by payers

Anatomical endpoints are scored low in value because:• Payers are unfamiliar with terms and clinical meaningfulness of these changes

and how vision is affected as a direct consequence

• KOLs are not sure about the objectivity of these measurements and question their correlation to dry AMD progression

“These are just surrogate endpoints and so far I have not seen convincing reasons for why they are important. If there were publications to suggest otherwise then my opinion would be different. The first thing I do when evaluating a new therapy is to put down the manufacturer’s submission and look at PubMed to see the validity of the claims for myself.”– Payer, Germany

“Can usually use OCT for AMD and DME but it is not clear what is the best measure to use for dry AMD and which one best correlates with disease progression. Nothing good at the moment.”– KOL, Germany

← Value →Low High

Perceptions of dry AMD endpoints

1 2 3 4 5


Notes on interpretation: Interviewees were asked to score the value of each endpoint on a scale of 1 (low) to 5 (high). Scores were averaged for payers (n=4) and KOLs (n=10).

Change in drusen size/area

AnatomicalHyper/hypo-pigmentation

Central retinal thickness




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Overview

Report Content


Conclusions and Recommendations

Majority of threats and payer uncertainty to funding patient access can be mitigated through clinical community support of effective therapies and payer education

Uncertainty around acceptability of predominantly anatomic endpoints

Publish, even if it is obvious to ophthalmologists that GA size matters, because payers need evidence to support their decisions

Size of patient population may necessitate restriction to subgroups to control budget impact

Help get therapies to those groups with higher need through research and publications

Once treatments come to market, later entrants will require H2H trials

Champion effective and safe treatments to best inform industry so that future trials use the most appropriate comparator and patients will be able to access the best medicines

Slower progression rates and reduced burden for earlier stages means that payers may be initially apprehensive about up front payments

Work to develop real world data from registries or small local studies to help to support access to therapies that are safe and effective, particularly for high cost medicines


Market Access Strategies for the Global Healthcare Environment

For further information

Steve Bradshaw, Director Market Access Solutions

1000 Great West Road, London, TW8 9DW

Tel: +44.203.675.8995

E: [email protected]

.mktxs.com

http://www.mktxs.com/






Dry AMD represents a considerable market opportunity especially for agents that can successfully target and prevent the progression of geographic atrophy

Opportunities Threats

Large and increasing patient population with no satisfactory therapies

Payers’ willingness to pay is thought to be high due to high unmet need and potential to avoid progression to expensive-to-treat wet AMD

Initial clinical outcome requirements may be more relaxed due to current lack of comparative treatments; for the first entrant a placebo-controlled trial will be satisfactory

Market opportunity is estimated at US$5 billion globally

Uncertainty around acceptability of predominantly anatomic endpoints

Size of patient population may necessitate restriction to subgroups to control budget impact

Once new treatments penetrate the market, later entrants will require H2H trials

Slower progression rates and reduced burden for earlier stages means that payers may be initially apprehensive about up front payments – especially for high-cost regenerative medicines

×



From a combined payer-KOL perspective, a placebo-controlled trial of at least 2 years in patients with moderate visual loss represents the best design (for a first entrant)

Feature Requirement Rationale

Pivotal design Placebo control (first entry) Because no SoC available, placebo trial would be acceptable Vitamin supplements can be used in both arms, as usually recommended

Duration 2 years minimum As a slowly progressing disease 2 years is judged the minimum acceptable Most interviewees also ask for an additional 1-3 years extension trial

PopulationStage: IntermediateSize: 250+ patients per armExclusions: Late-stage, other retinal diseases

Intermediate stage patients with moderate visual loss (e.g., 20/80 vision) recommended as motivated to complete study and likely to see better differentiation between study arms than early or late stage

Primary endpoints

Payers: BCVA stab/improvementKOLs: GA progression

BCVA most important for licensing and for payers GA progression (as measured) is a KOL favourite, but correlation with VA

would be needed to improve payer acceptance

Outcomes 3 lines difference in ETDRS20% relative change in GA

Payers familiar with 3 lines gain on ETDRS from previous experience with wet AMD trials; % change in GA in line with lampalizumab’s outcomes

Safety Ocular AEs: e.g., infectionsOther AEs: e.g., immunological

Any therapy requiring an invasive procedure in patients with early disease and low-moderate disease burden must have few side effects

“There’s no treatment at the moment so sham study is fine, but you compare against nutritional supplementation … and, because it's a slowly progressing disease I’d want data for 5 years.”– KOL, France

“The best ones are those with some element of visual loss and then you'd see a gradual decline in the control group. These patients are also more highly motivated to see out the trial because they have the early signs.” – KOL, UK

Requirements for a dry AMD clinical trial based on interviewee responses


Characteristic Wet AMD Dry AMD DME Non-infectious posterior uveitis

Vitreomacular traction

Prevalence

Clinical burden

Economic burden

Unmet need

Competitive environment

Payer management

HTA challenges

Overall opportunity of entering therapy area

MEDIUM: Competitive and

highly managed with effective SoC

HIGH: First to market product could have significant impact

MEDIUM: High population but

treatments available

LOW: Small population with off-

label treatments used

LOW: Small population and increased Payer

awareness


Opportunity in posterior segment disorders based on multicriteria assessment of perceived clinical burden, unmet need, market dynamics and payer environment

Large Medium SmallKEY:



To facilitate market access, manufacturers can offer support to physicians and patients in the form of education, administrative assistance and research funding

Markets Focus Manufacturer provided services

Educational programs for patients are well-received by French ophthalmologists and patient groups provide a forum for support

Educational and administrative support programs in place German payers are skeptical of manufacturer involvement at local level, preferring straight

discounting at the national or regional level

Novartis have entered partnerships with the NHS to provide static and mobile eye clinics to improve service to local areas• Currently 3 schemes are running in England and Wales

Novartis and Bayer provide local and personal assistance to patients who may have trouble paying for Lucentis and Eylea through Special Access Programs• If patients do not have full coverage (e.g. they are under 65 years old) then copayment rates of 10-

20% can be prohibitive on expensive VEGF therapies

• Manufacturers will investigate with the health insurers for personal plans so patients can access treatment

• This ensures patients can receive treatment at initial consultation without the need for complicated insurance assessment

Japanese ophthalmologists are open to approach from manufacturers who may offer prescriber/ patient incentives

= Patient-focused= Physician-focused

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Inherent differences between regenerative medicines and traditional pharmaceuticals present multiple challenges for access and reimbursement

Pricing, reimbursement and access issues Gene therapies

Traditional pharmaceuticals Implications

Involves multiple procedural steps that may be separately reimbursable Often Rarely

• Similar to reimbursement for a device/procedure

• Failure to achieve reimbursement of any component may jeopardize reimbursement of the entire procedure

HTA will focus on the cost-effectiveness of the entire procedure Yes Not often

applicable• Requires HEOR data collection regarding entire

procedure

May involve multiple billing codes/tariffs and/or payment centers for reimbursement of the full procedure

Yes No • Lack of appropriate codes/tariffs or payment may limit or preclude access and uptake

May involve requirements for longer-term data collection to demonstrate value (incl. post-market follow-up data)

Yes Sometimes • This is a top HTA criticism of most regenerative therapies in global markets to date

Strong potential to be more costly than standard of care alternatives Often Sometimes

• Higher cost means that therapies must demonstrate significant outcome improvements vs. standard of care

May enable a disease cure or prolonged therapeutic effect Yes Rarely • Can alter the balance of benefit-cost tradeoffs

in value assessment


Summary


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“They need to provide data beyond the regulatory approval standards – it does no good to compare a new and expensive therapy to a placebo if a comparator already exists.” – National Payer, Germany

Ophthalmologists are central to identification of

existing unmet needs, supporting clinical development and

monitoring through research and in shaping

payer beliefs, particularly where there are misconceptions

For high cost regenerative medicines (gene therapies

anticipated to cost>€1 million per dose), ‘payer centric’ clinical development

and consideration of innovative funding models

(pay for performance, annuity-based, risk pools …

even crowd funding) are needed to ensure patient

access

Payers have established their own therapeutic

guidelines, manage access more tightly and scrutinize the price of new therapies,

meaning pharma companies need to provide the

evidence sought by payers, specifically information such

as comparative effectiveness, cost

effectiveness and real world data

Evidence needs Clinical support Funding models

Ophthalmology Market Access by Dr Steven Bradshaw

Health & Medicine

Transcript of Ophthalmology Market Access by Dr Steven Bradshaw