significantly accelerating time to approval and ... · means companies face early commercialization...

An Integrated Development Plan in Rare & Orphan Medicinal Products (OMPs)

AUGUST 2020

© 2020 Syneos Health®. All rights reserved.

SIGNIFICANTLY ACCELERATING TIME TO APPROVAL AND STRENGTHENING ASSET VALUE FOR ALL KEY INDUSTRY STAKEHOLDERS

By Maryna Kolochavina, PharmD, PMP (Syneos One)

Syneos One®, a specialist group at Syneos Health, act as a single “go-to”

partner focused solely on helping biotech companies develop and execute

the most efficient integrated product development strategies in order to

maximize value and de-risk the delivery of critical patient therapies.

Our Syneos One team – a seasoned group of product development asset

strategists – provides customers with insights-driven product development

methodologies to speed time to market. Specific to rare and orphan drug

development where first mover advantage matters, Syneos One has

developed a proprietary diagnostic tool designed to identify the most

efficient clinical and regulatory path to approval while developing strong

value propositions for market access and market adoption.

* Based on the evaluation of a cohort of 218 assets with 436 orphan drug designations granted in 40 therapeutic classes that have been launched since 2016. Detailed analysis is included on pages 10 and 11 of this paper.

AN INTEGRATED DEVELOPMENT PLAN IN RARE & ORPHAN MEDICINAL PRODUCTS (OMPs)2

Companies looking to develop medicines for rare and orphan diseases face a range of challenging issues:

Leveraging our extensive insight into these issues in the rare and orphan space, Syneos One has developed the ADAPT (Accelerate, Drive, Anticipate, Partner, be Transparent) diagnostic tool—our integrated evidence-based tool* that provides a best-practice benchmark, specific to each customers’ opportunity, to maximize value for all stakeholders along the product development journey. The ADAPT diagnostic tool enables companies to:

• Clinical and regulatory strategy must be

developed and executed within a complex

and changeable regulatory framework,

competitive trial setting and politically

sensitive environment.

• Accelerated regulatory approval pathways

means companies face early

commercialization challenges that must be

addressed in a compressed time frame.

• Identify opportunities to accelerate patient

access to new therapies

• De-risk development and generate

necessary levels of evidence

• Optimize synergies between multifunctional

teams and regulatory and financial incentives

• Development programs can pose significant

risks when knowledge about the disease

state and rare patient population is limited,

leading to many associated research and

development (R&D) challenges.

• Companies require exceptional relationships

with geographically dispersed patients, their

families and the healthcare professionals

(HCPs) that comprise the disease community.

• Facilitate early patient engagement and long-

term partnership with all key stakeholders

• Provide support, advice and insights that build

trust within in the rare disease community

Contents

Introduction 4Abbreviations / Definitions 4

Overview of the Rare Disease Pharmaceutical Market 5

The “Rare” Reality 7What Does It Mean to Live with Rare and Orphan Conditions? 7

Key Stakeholder Perspectives and Expectations 8

Effectively Demonstrating Value within the Challenging Rare & Orphan Landscape 10R-W-W (Real-Win-Worth it) Screening Approach 13

Integrated Asset Planning and Delivery Is Essential to De-Risk Path Forward 15ADAPT-Based Integrated Solution Improves Asset Value 15

A Defined Partnership Model to Create, Capture and Maximize OMP Value 16

Conclusion 17

References 19


Regulations, multiple international initiatives and incentives have resulted in a marked increase in rare disease research funding and development effort,14 giving rise to great optimism about the future. However, challenges remain for the rare disease community:

• Despite technological and medical advances in recent years, misdiagnosis and a lack of knowledge remain12,13,41

• A rare disease has a significant impact on not only the person with the condition but that person’s family and primary caregiver4-5,7

• Drug development processes are not keeping pace with improved regulatory and clinical trial efficiencies2,13

• Clinical development is often hampered by an incomplete understanding of underlying disease mechanisms and relevant clinical endpoints, as well as limitations associated with identifying a large enough sample of comparable patients for clinical trials17,18,38

• High prices associated with rare and orphan drugs are a frequent barrier to market access43

Introduction Rare and orphan diseases are complex and represent significant unmet need, with over 7,000 such conditions known and 250 to 280 new diseases described annually; as many as 20 percent of these disorders are ultra-rare.2,6 Their impact, both in terms of disease burden and product development opportunity, is significant.

ABBREVATIONS

RD: rare disease ; R&D: research & development; WW: worldwide; CTs: clinical trials; OMP: orphan medicinal product; Ph: phase; KOL: key opinion leader; MAA: market authorization application; P&R: price and reimbursement; R&O: rare & orphan; HTA: health technology assessment; CUP: compassionate use program; EAP: early access program; RWE: Real World Evidence; PRO: patient-reported outcomes; SME: small and medium-sized enterprises


DEFINITIONS

Rare diseases by definition are conditions that affect small percentage of the population. There is no single, wide unifying definition of a rare disease; it differs by country and region prevalence range (from 1/1,000 to 1/200,000), and included other factors, such as the existence of adequate treatments, a lack of resources or the severity of the disease.2,6

The subcategory “ultra-rare” disease was introduced by the National Institute for Health and Care Excellence (NICE) for drugs with indications for diseases that have a prevalence of <1 per 50,000 persons (not the legal definition).60

“Orphan diseases,” often used as a synonym for rare diseases, have a distinct legal meaning in the United States and the European Union. The United States’ Orphan Drug Act definition of orphan disease includes both rare diseases and any non-rare diseases “for which there is no reasonable expectation that the cost of developing and making available in the United States a drug for such disease or condition will be recovered from sales in the United States of such drug.”61 The European Organization for Rare Diseases (EURORDIS) also includes both rare diseases and neglected diseases in a larger category of “orphan diseases.”62

OVERVIEW OF THE RAREDISEASE PHARMACEUTICAL MARKET

5

Growing segment

Novel development approach

High unmet need

Promising pipeline

– OMPs > 1/5 of WW

prescription sales56

– 163 percent sales

forecast vs. 146 percent

for non-orphan56

– $242B R&O market in 202456

– OMP is 4.5 times higher cost/

patient (to non-OMP 2018)57

– 73 percent approved

OMPs used at least 1

early access tool77

– 38 innovative R&D designs

for OMP65-75

– 18 early regulatory schemes46

– 61 percent positive OMP

HTA decisions with RWE78

– 42 percent approved OMPs

based on 1 CT only76

– 1 of 8 OMP approvals are

based on Ph1/Ph2 only76

– 400M people affected

WW,54 50 percent children,

30 percent of whom will

die before age 5 years2,4,5,52

– 80 percent RDs are genetic

origin 3-4 percent of births46

– 95 percent RDs no

approved treatment1-5

– less than one in 10

patients receive disease

specific treatment5

– 97 percent RDs not covered

with natural history flow19,20,48

– 85 percent RDs have no

organized group58

– 31 percent of the current

clinical trial pipeline55

– OMPs > 1/3 of R&D pipeline

sales (2024)56

– 1/3 of all MAAs in last 5 years57

since 2018 leading MAA:

16 percent in U.S.,

4 percent in EU57

Advances in scientific research over the last two decades have highlighted the emerging possibility of addressing the needs of patients and families with rare disorders in ways that would have been dismissed as science fiction only a few years ago.

Alastair Kent

Chair of Rare Disease UK, Director of Genetic Alliance UK63

AN INTEGRATED DEVELOPMENT PLAN IN RARE & ORPHAN MEDICINAL PRODUCTS (OMPs)

6

According to the International Rare Diseases Research Consortium (IRDiRC), in the next 10 years treatments will become available for only approximately 600 of the 7,000 known rare diseases.2 Improving treatment coverage and bringing novel medicines to patients in need remain important objectives in this still formative area.2 Traditional linear operational models and siloed activities will not address the existing unmet need. Integrated approaches that link R&D, Real World Evidence (RWE) and commercialization—including early engagement of key stakeholders—are emerging as requirements within this evolving and uncertain environment.81

Now, when the rare and orphan community is overwhelmingly concerned and impacted by COVID-19, it is essential to adopt innovations and implement predictive approaches to accelerate the development, ensure successful approval, market access and use of orphan medicinal products.79 The pandemic has intensified the challenges faced by the rare disease community with regard to resource prioritization, financial stability and increased competition in this non-mature market.80 At the same time, cooperation and broad evidence generation is required.

To address these challenges and meet the stakeholders’ expectations, Syneos One has created an integrated process for OMP development driven by our proprietary ADAPT diagnostic tool. This tool was formed based on an evaluation of 218 orphan assets with 436 orphan drug designations granted in 40 therapeutic classes that have been launched since 2016. The Syneos One team has structured the findings from these assessments into a system of 51 levers organized by category that can be applied to any rare and orphan asset. This allows us to benchmark the approach taken by drug development companies with industry best practice, and thereby identify the ways to accelerate time to market, opportunities to de-risk the asset value proposition and estimate an impact on asset value.

Our analysis shows that using an integrated management methodology in the rare and orphan disease space can result in significant acceleration times to approval and strengthen the asset value proposition for all key industry stakeholders.

This paper takes a close look at the OMP development landscape—what we call the “rare reality”—including key stakeholders’ expectations and perspectives, market demands, barriers and OMP critical success factors. We then explore how integrated product development using the ADAPT diagnostic tool can de-risk and accelerate go-to-market timelines. Finally, we review how Syneos One is supporting our customers to build on the outputs of this work through partnerships to deliver integrated programs, bringing OMPs faster to the patients who need them.

…The patients and families who are involved in that have to be ambassadors and get out there and show the rest of the research community how it works and how it was successful and what the impact was…we’re trying to change a whole culture of how researchers think and work…if they can get concrete examples of how it’s worked in the past and how it’s been successful and how it’s enhanced the research, they may be more open to just having it proposed to them...

—Patient 315


In Syneos One’s experience, involving these patients early helps improve OMP development, and leads to more economically viable clinical trials, and a fruitful, longer-term relationship at launch and beyond to help optimize current and new therapies.15,16,24

Living with a rare condition

7

According to a number of studies, more than 80 percent of patients and their families experience serious impacts to their daily lives as a result of their rare diseases.7-11 These impacts include the substantial time burden of daily care management and care coordination.2

WHAT DOES IT MEAN TO LIVE WITH RARE AND ORPHAN CONDITIONS?

“I do not know about my condition”The burden for patients

suffering from any form

of a rare disease typically

starts with a late

diagnosis.4-5,7,12 Finding and

engaging these patients

early with a sophisticated,

robust, inexpensive and

easy diagnostic workflow

remains a challenge.13

“I am the only one in my country who is ultra-rare”In many cases, ultra-rare

diseases remain a mystery

to researchers, with limited

models or guidance, little

research and a poor

understanding of the natural

history of the disease.19,20

The complexity of rare

diseases can cause significant

mental and physical burdens

for patients and their families.

Most individuals will not be

cured in their lifetimes.2,45

“My physician lacks understanding about my condition”Healthcare providers often

lack knowledge of how to treat

people with rare diseases due

to their low prevalence,

meaning that patients often

have an active role and partner

with their healthcare team in

their treatment journey.14,46

“I feel I’m an expert in my own disease”The availability of cyber-based

health information and online

groups has led to the

emergence of the “expert”

patient who may, in fact, know

more about their condition than

many of the healthcare

providers they come into

contact with.4,5,7 These patients

seek a collaborative relationship

with their healthcare teams,

meaning that traditional roles

and communication

approaches have to evolve to

become more patient-centered

—and in some cases may be

patient-directed.21,25,51

“I might not have research treatment during my life”While the number of rare

disease treatments is growing

substantially, they treat only a

small fraction of rare diseases,

most of which have few or no

treatments.2,19 Most rare

diseases do not have drugs

in development to treat them,

highlighting the need for

continued incentives to address

research and treatment gaps.1-5

“I may not have approved and available treatment”Evidence uncertainties during

regulatory and reimbursement

decision-making combine to

limit access to effective

therapies.16,17 These

uncertainties arise from a lack

of robust information around

clinical benefit, value for money,

and potential adoption.18

Prescribing restrictions and drug

delivery systems also influence

the ease of patient access to

reimbursed orphan drugs.32,39

“I want to help others with my condition”Patient involvement

can improve discovery,

development and evaluation

of effective medicines by

supporting a more collaborative

understanding of unmet needs

and R&D objectives.21,22,41

“My family and I need constant psychological and physical support”Many patients with rare

diseases suffer from multi-

system dysfunction, without

effective treatment, and are

likely to require complex

care.9,11 Multiple factors lead

to additional physical and

psychological impairments

for patients and families.41

“I encounter social and emotional challenges unique to my condition”For some patients and families,

obtaining a diagnosis brings

relief; for others it can be a

crushing reality check as 95

percent of rare diseases have

no approved treatment.2,13

THE “RARE”REALITY


8

Key stakeholder perspectives and expectationsBefore undertaking a fully integrated approach to product development in the rare disease space, it is critical to have an in-depth understanding of the expectations and perspectives of key stakeholders in the rare and orphan disease community.

Regulators are highly willing to make decisions based on provided integrated evidence that has the characteristics needed to rely on it.— Janet Woodcock M.D.

Director, CDER, FDA25


Acceleration is

evidence-driven29,47

“Evidence vs.

access” conundrum34

Asset robust evidence and

clear added value (OMP being

novel / improved / different)43

Acceleration to improve

methods of diagnosis and care42

Expedited approval does not

mean “less evidence”33,59

“Live the best life possible”

understanding33

Meaningful evidence for

coverage per patient (sub)

group and population37

Better understanding of the

disease, patient’s needs and

OMP nature42

Respond to the complexity with

novel approaches to increase

R&D and RWE productivity25,31

Opportunity to collect

patient-centric data and

take advantage of fast-

evolving technologies21-23

Uncertainty associated with

realizing benefit from high-

cost treatment (downstream

health benefits, lifelong

treatment benefits)40

Address highly competitive

“lower-hanging fruits”44

Scientific short- vs. long-term

strategies45

Cooperation in generating

benefit / risk evidence27,29

Inclusion of patient voice26

Active engagement from first

experience with orphan

medicinal product24

Collaboration on OMP

economic value and agreement

with regulators on endpoints

and comparators32

Commitment to streamline

drug-to-patient with increased

efficiency of data collection

and sharing between KOLs41

Proactive steps needed

to streamline collaboration

on integrated evidence

generation plan, review and

approval process28,30

“Time Equals Lives”: Patient

knowledge, contribution at

every OMP life cycle step are

crucial to increase product

development efficiency36

React to changes in R&O

landscape: e.g., new models

of risk and incentive sharing

between public and private

partners, repurposing of existing

agents, transformative P&R

schemes and innovative MEAs44

Improve care standards with

data from disease registries49

Clinical protocol design

evidence, meaningful to

patients and KOLs39

FOR REGULATORS FOR PATIENTS FOR PAYERS & HTAs FOR PHYSICIANS


The Expectation: Transparent in Communication With All Parties Involved

The Expectation: Engage Stakeholders Early and Partner Throughout The Asset Life Cycle

The Expectation: Anticipate Risks and Complexities in Changeable Environment

The Expectation: Generate Robust Evidence

The Expectation: Accelerate Time to Market

KEY STAKEHOLDER PERSPECTIVES

Such expectations create a unique need for early cooperation to maximize orphan medicinal product potential.14,35

In response to the complexities of the R&O sector, Syneos One deploys its proprietary ADAPT (Accelerate, Drive, Anticipate, Partner, be Transparent) diagnostic tool to enable companies to:

• Accelerate time to market by applying and implementing efficiencies, opportunities and incentives that are available in the R&O space

• Drive data collection and generate the evidence required at each inflection point for the asset during the life cycle

• Anticipate risks, unknowns and evolving therapeutic landscape

• Partner with all key stakeholders early and throughout an asset’s life cycle

• Be transparent in processes and communication between all stakeholders involved

To create the ADAPT diagnostic tool, the Syneos One team evaluated a cohort of 218 assets with 436 orphan drug designations granted (74 percent of assets have more than 1 designation per asset) in 40 therapeutic classes that have been launched since 2016 (Fig. 1-2).

Effectively Demonstrating Value within the Challenging Rare & Orphan LandscapeAs mentioned above, orphan medicinal products pose unique challenges when it comes to demonstrating value, owing to an often-limited evidence base, small dispersed patient populations, lack of knowledge about the condition and its natural history,19,20 and affordability and variable availability.51,52

10AN INTEGRATED DEVELOPMENT PLAN IN RARE & ORPHAN MEDICINAL PRODUCTS (OMPs)

Many factors affect OMP value. Until now, there has been little consensus on the most appropriate assessment criteria.

—ORPH-VAL, 201782

11

Figure 1-2. ADAPT Sample


THERAPEUTIC CLASS FOR 218 ASSETS

LAUNCHED SINCE 2016 (ADAPT SAMPLE)

436 ORPHAN DRUG STATUS GRANTED TO

218 ASSETS LAUNCHED (ADAPT SAMPLE)

Antianemic Antiarthritic Antibody, non-monoclonal Anticancer Antidepressant Antidiarrheal Antiepileptic Antifungal Anti-inflammatory Antimalarial Antithrombotic

Antiulcer Antiviral Antiviral, anti-HIV Blood fraction Cardiovascular Cellular therapy Cystic fibrosis treatment Dermatological Diagnostic Fusion protein

Gene therapy Hepatoprotective Hormone Infection Metabolic and enzyme disorders

Monoclonal antibody Muscle relaxant Musculoskeletal Neurological Neuroprotective

Protozoacide Recombinant Reformulation Respiratory RNA interference Urological Antisense therapy, Other Antisense therapy, Musculoskeletal

12

The Syneos One team structured the findings from these assessments into a system of 51 levers by five categories (Fig. 3):

LEVER EXAMPLES

Consensus on

definitions and

diagnosis

Novel feasibility

Dynamic Assembly

LEVER EXAMPLES

Stakeholders regular

alignment during

the life cycle and

arrangement for the

benefit of a patient.

Avoid asymptomatic

information

Integrated evidence

generation plan (value

over time requirements,

each phase in right

order completion)

LEVER EXAMPLES

Early patient

engagement

Synergy between

orphan drug

designation, expedited

regulatory designations

and early market access

LEVER EXAMPLES

Completion and

superiority evidence

Disease / OMP budget

impact vs. preferences:

society / family / patient

LEVER EXAMPLES

Net outcomes

improvement evidence,

meaningful to patients

and KOLs

Early knowledge (e.g.,

surrogate or composite

intermediate endpoints,

that are qualified and

validated in advance)

data collection and

generate the evidence

required at each

inflection point for the

asset during the life

cycle to support

acceleration in time

risks, unknowns, new

condition information,

regular revisions of

experience, new market

realities and trends,

shifts in stakeholders’

need, new data

and technology

with all key stakeholders

early in the process

and through OMP

lifetime / life cycle

time to market with

single or a combination

of the R&O efficiencies,

opportunities and

incentives,

opportunities and

incentives tailored per

OMP, therapy area and

patient needs

We start with accelerating time as our patient is there and is waiting

Acceleration is always evidence driven. We need to show evidence to receive expedited

pathway designations

While working with evidence in the R&O space, we need to keep the door open to uncertainties

We expect unknowns and uncertainties. Yet, to accelerate our time to patient, we need clear

partnering with all stakeholders

To support partnering with all stakeholders, we need clear communication and processes

Drive Anticipate PartnerAccelerate

How we came to these

Categories

in processes and

communication

between all parties

involved to deliver the

best care to the patient

with unmet need

Be Transparent

ACCELERATION IS ALWAYS

EVIDENCE DRIVEN

WORKING WITH UNCERTAINTIES IS

ESSENTIAL

EARLY ENGAGEMENT STRUCTURE

REQUIREMENT

TRANSPARENT COMMUNICATION AND PROCESSES

1

2

3

4

5


Figure 3. ADAPT Levers Examples

Our analysis suggests that applying between 23 and 51 of these levers could significantly reduce the time to approval and strengthen the value proposition of the asset for all key stakeholders (Fig. 4).

13

Figure 4. Best Practice, Sector Standard, Below Average Cases

218

2 31

23 5112

Below Average

Number of Levers Used

Num

ber o

f OM

Ps

Sector Standard Best Practice

Significant acceleration times to approval and strengthen the asset value proposition to all key industry stakeholders

ADAPT enables us to benchmark an asset’s clinical and regulatory strategy against best practice. We perform this by determining the applicability of each of the 51 levers for the asset in question using an R-W-W (Real-Win-Worth it) screening approach.

From the findings of the ADAPT tool, we typically build an integrated asset roadmap that includes activities to address the areas highlighted by the diagnostic. The roadmap is “integrated” in the sense it incorporates:

• Patient-focused fast adaptive R&D

• Accelerated regulatory pathways and scientific advice

• Patient engagement measures

• Value proposition and market access optimization (Fig. 5)

Importantly, it determines if there is a potential valuation lift of the asset by considering alternative clinical and regulatory approaches.

“Real” analysis

Determines if each lever’s activity has been completed, is ongoing, is planned

by company or is feasible and timely

“Win” analysis

Identifies the additional value of each lever to help reduce the time-to-market, find ways to de-risk development and

realize efficiencies

“Worth it” analysis

Tests each lever’s viability according to effort/result ratio


R-W-W (Real-Win-Worth it) screening approach


Figure 5. Asset road map: high-level illustration

PRE- CLINICAL PHASE I PHASE II PHASE III PHASE IV COMMERCIALIZATION

& POST-APPROVAL

OMP Case for UseOMP Case for ReimbursementOMP Case for ApprovalCurrent Drug Development

ADAPT Diagnostics

Outcome

R&D Program and Strategy

OMP Case for Approval

Adaptive Trial(s) Design and R&D strategy

Accelerated regulatory pathways

Expedited HTA/P&R

EAP/CUP/Hospital Exemptions Early Market Access

Additional therapeutic benefits

Clinical and Real-World Research and Evidence Generation

Post-Authorization Evidence Generation

Commercialization, Market Access and Pricing

OMP Case for Reimbursement OMP Case for Use

MAA Review P&R


INTEGRATED ASSET PLANNING AND DELIVERY IS ESSENTIAL TO DE-RISK PATH FORWARDOnce the asset road map has been developed, a detailed integrated planning process can be initiated. This requires multidisciplinary collaboration to capture all the required functional area insights, enabling companies to:

• Promote a sense of urgency by selecting an innovative research and development design that includes timely and relevant reported outcomes (meaningful to patient, observer and physician)

• De-risk R&D with early protocol reviews, scientific consultation and frequent interactions with regulators and payers

• Take advantage of the efficiencies and incentives such as orphan drug designation, regulatory early access tools and expanded market access programs

• Implement priority insights to help strengthen the case for investment

• Ensure key stakeholders’ needs are addressed early on

For stakeholders, using the ADAPT tool results in:

ADAPT-BASED INTEGRATED SOLUTION IMPROVES ASSET VALUE

Patient, Family, SocietyEarly access with evidence that

the treatment is effective and

results in better quality of life

Patient OrganizationsPatient-focused adaptive

and efficient evidence

generation for OMP coverage

without restrictions

InvestorsImprovements in asset value

through optimized planning,

accelerated delivery and

de-risked operations

IndustryNiche and sustainable

advantages to expand and

maximize OMP value

BoardIntegrated evidence to

optimize OMP value via clinical

/ commercial competitive

advantage in cost, time,

resources and quality

Small / Mid-size companies (SME)Biotechnology integrated

business model with single

contact managing

multifunctional teams

onward for maximum NPV

RegulatorsStrong OMP evidence for

approval based upon dynamic

results that evolve with new

data and RWE

KOLsRobust evidence to support

rare disease understanding

and clear differentiation of

OMP in the treatment pathway

16

A DEFINED PARTNERSHIP MODEL TO CREATE, CAPTURE AND MAXIMIZE OMP VALUESyneos One uses a specific partnership model with companies looking to develop rare and orphan medicines. Building from the diagnostic outputs of the ADAPT tool, we work with our customers to design and execute an integrated product development approach for their assets spanning clinical and commercial activities. Leveraging this approach, our customers immediately gain global operational scale, allowing them to help de-risk the use of funds for their clinical and commercial activities.

Our model is based on a close strategic partnership between our client and the Syneos One team. This partnership is driven by our “Asset Lead,” who works closely with the customer to support the development of the optimal clinical, regulatory and commercial strategy and the enablement of successful integrated operational delivery. This streamlined product development approach ensures that our clients receive a tailored service in an “easy to do business with” model but with the benefit of the global scale of Syneos Health. We supplement our customers’ existing expertise with broad clinical, market

access, regulatory and commercial capability, and integrated thinking with no stone unturned. This tightly integrated approach across the entire product development program is essential in the rare and orphan space.

The effort typically involves a series of distinct phases where the end of each phase is linked to a value inflection point for the asset. This provides our customers with clear opportunities to review achievements and change course if desired.

The best strategic idea means nothing in isolation.

—Nilofer Merchant

Harvard Business Review, 201150


ConclusionThe scale of the “rare disease problem”—thousands of rare diseases, the vast preponderance of them with no approved treatment and decades‐long diagnostic odysseys for many patients—has led to the realization that the time has arrived for global cooperation and collaboration among the many stakeholders active in rare disease research, to capitalize on proofs of principle and maximize the output of rare disease research efforts around the world.51

Government research funders, companies, scientists and patient advocacy groups have all demonstrated their commitment and effectiveness in contributing to progress in rare diseases research. We are all in this together—enabling earlier access to new, effective treatments.


ABOUT THE AUTHOR

Maryna Kolochavina

Executive Director, Syneos One, Rare Diseases

18

Maryna has over 15 years in life cycle management of a number of complex rare and orphan

conditions, including pediatric rare and ultra-rare diseases. Maryna has strong experience in

planning and execution of multiple studies/project phases (pre-clinical, I, IIA/IIB, IIIA/IIIB, IV) and

designs, such as disease and product observational registries with prospective and retrospective

data collection, pregnancy registries, observational FUP and retro chart review studies;

compassionate use programs (including Named Patient Program, Expanded Access Programs,

ATU, Special Access, IND); safety surveillance studies (including active and passive surveillance

studies, descriptive drug utilization studies, PASS, PAES); non-interventional studies (NIS) with

ePRO, HEOR and EPI modules; rare ATMP and stem cells studies, device studies, computer adaptive

testing and Omics studies (tissue research). Her educational background includes PharmD in

clinical pharmacology from National Medical Academy, Gdansk, Poland, and translational work in

rare skin diseases. Maryna is certified ACRP, BARQA, ASQ and PMI. She is an active patient advocate

for rare and orphan patients in the Patient Voice program at Charité, Berlin, Germany.

For more information about Syneos One and the ADAPT Diagnostic Tool, please go to syneoshealth.com.


19

REFERENCES

1. https://www.orpha.net/orphacom/cahiers/docs/GB/List_of_rare_diseases_in_alphabetical_order.pdf

2. Future of Rare Diseases Research 2017–2027: an IRDiRC Perspective Clin Transl Sci. 2018 Jan; 11(1): 21–27 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5759730/

3. Tambuyzer E. Rare diseases, orphan drugs and their regulation: questions and misconceptions. Nat. Rev. Drug Discov. 9, 921–929 (2010)

4. Boycott K.M. et al International cooperation to enable the diagnosis of all rare genetic diseases. Am. J. Hum. Genet. 100, 695–705 (2017)

5. Melnikova I. Rare diseases and orphan drugs. Nat. Rev. Drug Discov. 11, 267–268 (2012)

6. https://www.researchamerica.org/sites/default/files/Rare%20Diseases%20Fact%20Sheet_2015.pdf

7. http://download2.eurordis.org.s3.amazonaws.com/rbv/PR_INNOVCare_Final.pdf

8. Kramer M. The National Organisation for Rare Diseases and the experiences of the rare disease community. National Organisation for Rare Diseases (NORD); 2003. http://www.rarediseases.org/pdf/Eval_Final_Paper.pdf.

9. Kole A, Faurisson F. The Voice of 12,000 Patients: Experiences and expectations of rare disease patients on diagnosis and care in Europe. Eurordis; 2009. http://www.eurordis.org/publication/voice-12000-patients.

10. Limb L, Nutt S, Sen A. Experiences of Rare Diseases: An Insight from Patients and Families. Rare Diseases UK; 2010. http://www.raredisease.org.uk/documents/RDUK-Family-Report.pdf.

11. Eurordis Survey of the Delay in Diagnosis for 8 Rare Diseases in Europe (‘EurordisCare 2’) 2006. http://www.eurordis.org/IMG/pdf/Fact_Sheet_Eurordiscare2.pdf.

12. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3599672/

13. https://www.thelancet.com/journals/landia/article/PIIS2213-8587(19)30006-3/fulltext

14. https://www.ncbi.nlm.nih.gov/books/NBK208609/

15. https://ojrd.biomedcentral.com/articles/10.1186/s13023-017-0738-6

16. Lee D, Wong B. An orphan drug framework (ODF) for Canada. J Popul Ther Clin Pharmacol. 2014;21:e42–6.

17. Morel T, Arickx F, Befrits G, Siviero P, Van Der Meijden C, Xoxi E, et al. Reconciling uncertainty of costs and outcomes with the need for access to orphan medicinal products: a comparative study of managed entry agreements across seven European countries. Orphanet J Rare Dis. 2013;8:198.

18. Meekings KN, Williams CS, Arrowsmith JE. Orphan drug development: an economically viable strategy for biopharma R&D. Drug Discov Today. 2012;17:660–4.

19. Dunoyer M. Accelerating access to treatments for rare diseases. Nat Rev Drug Discov. 2011;10:475–6.

20. Institute of Medicine Committee on Accelerating Rare Disease Research and Orphan Product Development. Rare diseases and orphan products: accelerating Research and Development. 1st ed. Washington: The National Academies Press; 2010.

21. Yeoman G et al. BMJ Innov. 2017;0:1–8

22. https://patientfocusedmedicine.org/patient-centricity-collaborative-definition/

23. https://innovations.bmj.com/content/3/2/76

24. https://www.ncbi.nlm.nih.gov/pubmed/26539338

25. https://www.nap.edu/resource/25352/interactive/

26. https://www.fda.gov/drugs/development-approval-process-drugs/fda-patient-focused-drug-development-guidance-series-enhancing-incorporation-patients-voice-medical

27. https://events.lygature.org/wp-content/uploads/2019/11/3_Partnerships-meet-up-Oct-19_Nathalie-Bere.pdf


29. European Medicines Agency. Human regulatory, Research and development: Scientific guidelines. https://www.ema.europa.eu/human-regulatory/research-development/scientific-guidelines

30. https://www.ema.europa.eu/en/documents/report/stakeholder-engagement-report-2017_en.pdf

31. Jarow JP, LaVange L,Woodcock J. Multidimensional Evidence Generation and FDA Regulatory Decision Making: Defining and Using “Real-World” Data. JAMAJuly2017. http://dx.doi.org/10.1001/jama.2017.9991.

32. https://www.sciencedirect.com/science/article/pii/S1098301517333478

33. https://pink.pharmaintelligence.informa.com/PS140810/The-New-Payer-Dogma-US-FDA-Approved-Drugs-Have-Less-Evidence


35. https://www.ema.europa.eu/en/documents/report/report-workshop-stakeholders-support-quality-development-early-access-approaches-ie-prime_en.pdf

36. https://pink.pharmaintelligence.informa.com/PS141419/Individual-Endpoints-Pose-Challenge-For-US-FDA-In-Review-Of-Rare-Disease-Drug

37. https://www.ema.europa.eu/en/news/emafda-analysis-shows-high-degree-alignment-marketing-application-decisions-between-eu-us


39. https://www.ema.europa.eu/en/documents/comments/overview-comments-received-reflection-paper-proposal-enhance-early-dialogue-facilitate-accelerated_en-0.pdf





44. https://www.tandfonline.com/doi/full/10.1080/20016689.2019.1643215?af=R

45. https://ojrd.biomedcentral.com/articles/10.1186/s13023-019-1040-6

46. https://www.europabio.org/healthcare-biotech/publications/development-process-orphan-medicinal-products


48. http://www.fdalawblog.net/2019/03/breaking-down-fdas-new-rare-disease-natural-history-studies-guidance-practical-considerations/


50. https://hbr.org/2011/03/culture-trumps-strategy-every


52. https://www.who.int/medicines/areas/priority_medicines/Ch6_19Rare.pdf

53. https://www.fda.gov/drugs/development-approval-process-drugs/cder-patient-focused-drug-development

54. https://www.ifpma.org/subtopics/rare-diseases/

55. Tufts CSDD Impact Report July/August 2019, Vol. 21 No. 4.

56. https://www.evaluate.com/orphan-drugs

57. https://www.evaluate.com/thought-leadership/pharma/evaluatepharma-orphan-drug-report-2019

58. http://www.pharmatimes.com/web_exclusives/The_rare_disease_challenge_1323505

59. https://www.fda.gov/news-events/fda-voices/delivering-promising-new-medicines-without-sacrificing-safety-and-efficacy



ABOUT THE SYNEOS HEALTH INSIGHTS HUB

The Syneos Health Insights Hub generates future-focused, actionable insights to help biopharmaceutical companies

better execute and succeed in a constantly evolving environment. Driven by dynamic research, our perspectives are

informed by our insights-driven product development model and focused on real answers to customer challenges

to help guide decision making and investment.

ABOUT SYNEOS HEALTH

Syneos Health® (Nasdaq:SYNH) is the only fully integrated biopharmaceutical solutions organization. The Company,

including a Contract Research Organization (CRO) and Contract Commercial Organization (CCO), is purpose-built to

accelerate customer performance to address modern market realities. Learn more about how we are shortening the distance from lab to life® at syneoshealth.com.

20

REFERENCES (continued)

61. https://www.fda.gov/media/99546/download

62. https://www.eurordis.org/IMG/pdf/princeps_document-EN.pdf

63. https://www.raredisease.org.uk/media/1594/rduk-family-report.pdf

64. https://www.researchgate.net/publication/321237255_A_systematic_literature_review_of_evidence-based_clinical_practice_for_rare_diseases_What_are_the_perceived_and_real_barriers_for_improving_the_evidence_and_how_can_they_be_overcome

65. FDA (2019a) Guidance for Industry – Rare Diseases: Common Issues in Drug Development. The U.S. Food and Drug Administration, Silver Spring, Maryland, USA.

66. Huang Z, Chow SC (2019) Probability monitoring procedure for sample size determination. Journal of Biopharmaceutical Statistics 29: 887-896.

67. Chow SC, Huang Z (2019) Demonstrating effectiveness or demonstrating not ineffectiveness - A potential solution for rare disease drug development. Journal of Biopharmaceutical Statistics 29(5): 897-907.

68. Chow SC, Shao J, Wang H, Lokhnygina (2017) Sample Size Calculations in Clinical Research. 3rd Edition, Chapman and Hall/CRC Press, Taylor & Francis, New York, USA.

69. Chow SC, Huang Z (2020) Innovative approach for rare disease drug development. Journal of Biopharmaceutical Statistics 30(3).

70. Corrigan Curay J (2018) Real-world evidence – FDA update. Presented at RWE Collaborative Advisory Group Meeting, Duke-Margolis Center, Washington DC, USA.

71. FDA (2010) Draft Guidance for Industry – Adaptive Design Clinical Trials for Drugs and Biologics. United States Food and Drug Administration, Silver Spring, Maryland, USA.

72. FDA (2019c) Adaptive Designs for Clinical Trials of Drugs and Biologics. United States Food and Drug Administration, Silver Spring, Maryland, USA.

73. Woodcock J, LaVange LM (2017) Master protocols to study multiple therapies, multiple diseases, or both. N Eng J Med 377(1): 62-70.

74. FDA (2018) Guidance for Industry – Master Protocols: Efficient Clinical Trial Design Strategies to Expedite Development of Oncology Drugs and Biologics. The United States Food and Drug Administration, Silver Spring, Maryland, USA.

75. FDA (2019b) Framework for FDA’s Real-World Evidence Program. United States Food and Drug Administration, Silver Spring, Maryland, USA.

76. https://www.raps.org/news-and-articles/news-articles/2019/5/almost-half-of-all-new-drug-approvals-in-2018-reli

77. https://www.fda.gov/files/drugs/published/New-Drug-Therapy-Approvals-2018_3.pdf


79. https://rarediseases.org/wp-content/uploads/2020/05/NRD-2061-RareInsights-CV19-Report_v2-2.pdf

80. https://www.ecdc.europa.eu/sites/default/files/documents/covid-19-rapid-risk-assessment-coronavirus-disease-2019-ninth-update-23-april-2020.pdf

81. https://www.bundesgesundheitsministerium.de/fileadmin/Dateien/3_Downloads/N/NAMSE/National_Plan_of_Action.pdf

82. https://pubmed.ncbi.nlm.nih.gov/28283046/


significantly accelerating time to approval and ... · means companies face early commercialization...

Documents