Rare Diseases and Orphan Drugs Global Forum 2017

Co-chaired by:
Alistair Kent, Director, Genetic Alliance
Larissa Kerecuk, Rare Disease Lead, Birmingham Children's Hospital NHS Foundation Trust

The patient's perspective is at the heart of Orphan Drug development. However, researchers struggle to apply the acknowledged principles of scientifically sound outcomes research in clinical trials. As a consequence, decision makers (regulators, payors, prescribers, and ultimately patients) frequently rely on testimonials communicated by the patients, their representatives, or their caregivers, to make group-level or individual-level decisions. Due to the specific features of rare diseases, standardized measures do not appropriate solutions. Mixed Methods research combine the strength of qualitative and quantitative methods to address the research question. Embedding qualitative interviews in the Phase II/III clinical trials is a rapidly developing, promising approach to capture the patient perspective within the scientific research framework.Drug development in Rare Diseases faces many challenges: fewer patients to study, less well understood diseases, often little precedence in how to quantify disease progression or to demonstrate treatment responses efficiently and consistently. All those aspects necessitate different approaches to design, execution and analysis of clinical trials in Rare Diseases helping to better understand the performance of new drug treatments and to generate the necessary evidence to achieve approval.

Model informed drug development (MIDD) has been around for two decades to facilitate integration of quantitative information on clinical endpoints, biomarkers, demographics, characterising disease progression, response to treatment and to inform benefit/risk assessments. To identify characteristics of the target patient population, to predict disease progression, but also to optimise clinical trials for instance by selecting the best endpoint, or composite, quantitative models are often used in the design and analyses stages of clinical trials. The achievements using MIDD are numerous, but the implementation across industry is still sparse for various well or less well founded concerns.

The talk will emphasise how model based approaches were successfully utilised across a range of clinical development programs for Rare Diseases guiding drug candidates through all stages of development, with the aim to deliver promising treatment options to benefit patients in need consistent, fast and more efficient.

Alistair Kent, Director, Genetic Alliance
In this talk I will explore how engaging with patients and families affected by rare and complex life limiting diseases can help optimise the organisation of both research and development and the planning and delivery of high quality care and support. Everywhere healthcare systems are under increasing pressures. This is due to a coming together of a number of factors. The pace of change and the opportunity to intervene is growing. Demographic change, a growing elderly population with multiple morbidities, increasing patient and consumer demand, and static or declining resources are coming together to produce a "perfect storm" for solidarity driven health care systems. Systematic engagement with patients and families will help ensure that improvements in research and changes in how healthcare is delivered are both efficient and effective, potentially creating "headroom" for innovations targeted at unmet needs to be introduced.

Dr. med. univ. Jama Nateqi, Co-Founder, SYMPTOMA
- Why most patients with orphan diseases go undiagnosed and others take 10 years from symptom to diagnosis.
- What new ways can be utilised for physicians to diagnose orphan diseases?
- How to empower patients and physicians to actively uncover their underlying orphan disease.
- Why orphan drugs need new techniques of marketing & patient finding.

Pete Chan, Head of Research and Analysis, Raremark
People living with a rare disease often face a diagnostic odyssey as part of their journey, typically waiting several years for a diagnosis and receiving multiple diagnoses along the way. Crowdsourced data on typical routes to diagnosis of rare disease patients promise to highlight knowledge gaps in healthcare systems, including which physicians are missing opportunities to make an accurate diagnosis, and the areas in which medical education programs may have the greatest impact. Sharing patient data to help doctors recognize the symptoms of rare diseases will shorten delays in diagnosis, allowing patients more timely access to appropriate treatments.

Dan Jeffries, Patient, Wyburn-Mason syndrome
Wyburn-Mason syndrome. Ever heard of it? Dan Jeffries has, and his insightful and entertaining talk explores what it's like living with one of the world's rarest medical conditions - and then finding out you have another one. Dan talks about the early days of diagnosis, living with Wyburn-Mason syndrome, how things started to change during his twenties and then the startling discovery of his other rare condition just as he was turning thirty.

Larissa Kerecuk, Rare Disease Lead, Birmingham Children`s Hospital NHS Foundation Trust
- Challenges of Rare Diseases faced by people affected by rare diseases & co-design of centre with children & families
- 100K Genome
- Research and collaboration vital for rare diseases progress
- Patient History- A Patient Speaks

Jefferson Davis, Chief Business Officer, Acer Therapeutics, Inc.
The development of a drug with an existing data package ("repositioning") typically requires less capital than traditional approaches. While a repositioned drug may be less capital intensive, there are unique challenges and obstacles to overcome in order for the therapy to reach patients. There are many examples of repositioned drugs that improve the lives of patients; however, the current business environment necessitates the need different and innovative strategies for repositioned drugs. This talk will aim to provide; (i) an historical perspective on the value of repositioned drugs to the patient community and other stakeholders, (ii) key points to consider when repositioning drugs, (iii) a review of recent case studies, and (iii) predictions for the future of repositioning drugs for rare disease.

Christian Girard, Corporate Advisor-Orphan Drugs-Alternative Financing, ORPHAN DRUGS
INDUSTRY Advisory & Intelligence
- What?
- Why?
- How?
- Cases

Moderator:
Larissa Kerecuk, Rare Disease Lead, Birmingham Children's Hospital NHS Foundation Trust

Panelist:
Dr. med. univ. Jama Nateqi, Co-Founder, SYMPTOMA

Panelist:
Key Parkinson, CEO, Cambridge Rare Disease Network

Panelist:
Alistair Kent, Director, Genetic Alliance

Panelist:
Pete Chan, Head of Research and Analysis, Raremark

Co-chaired by:
Malcolm Allison, Director and Owner, InterComm International Ltd and
Cesare Spadoni, Chairman, aPODD Fundation

Parents and non-profit entities can play a strong role in driving drug development and thus accelerate the availability of more innovative drugs for children with cancer. But in order to do so they must adopt new operating models and collaborate more effectively with other stakeholders. A few examples of this new approach are provided.

Life has been good to me, and to most people in the room. We chose a profession where we can make a difference. Whether we are actually designing or developing drugs, or just communicating about them, the fruit of our efforts is improved health for people less fortunate than ourselves. If we are doing good, we will do well.
It should all be plane sailing. Constant adjustments to the boat should bring us smooth progression through the water. As we get better, we make the adjustments more smoothly and the impact means a smoother and more effective progression through the water.

Our progress is of course influenced by the environment. For those of us in pharmaceuticals, the levers we can pull depend on the quality of evidence we have, and the way in which we use it. Just as the size of the sail and the quality of fixing allow us to gather more wind or change course more smoothly. And just like the sailing analogy, if we don’t have the evidence, or the larger sail, when we set off we will not have it at our disposal when we need it later. There is no going back once you have sailed.

My presentation is about the changes in what we should have on board, before we set sail. For rare or orphan diseases the water is less certain and less predictable now than it has ever been. In my presentation I want to examine the elements that have changed and try to predict how we plan for them.

I will touch briefly on three factors that play a greater role in the development and marketing of therapies for rare diseases:
- Build a strong relationship with regulators
- Establish a value proposition
- Engage with patients to design and build the programme

The patient's perspective is at the heart of Orphan Drug development. However, researchers struggle to apply the acknowledged principles of scientifically sound outcomes research in clinical trials. As a consequence, decision makers (regulators, payors, prescribers, and ultimately patients) frequently rely on testimonials communicated by the patients, their representatives, or their caregivers, to make group-level or individual-level decisions. Due to the specific features of rare diseases, standardized measures do not appropriate solutions. Mixed Methods research combine the strength of qualitative and quantitative methods to address the research question. Embedding qualitative interviews in the Phase II/III clinical trials is a rapidly developing, promising approach to capture the patient perspective within the scientific research framework.

Synopsis: In addition to clinical development, successful pharmaceutical products and medical devices need economic profiling for market access. There is the tendency that economic profiling starts at an ever earlier stage of clinical development. This phenomenon can be termed "early market access" and is motivated by a variety of reasons such as: (1) an expression of value for money for the new product (2) due diligence purposes in relation to a startup company, (3) mapping out early pricing and reimbursement research strategies etc. This presentation discusses methods of early market access based on a number of case studies and looks at when this new discipline is particularly relevant.

The rare disease community is very knowledgeable with respect to the development of new and exciting treatments. An early access program, often referred to as Compassionate Use, Expanded Access or Named Patient, allows pharma and biotech companies to meet the needs of their patients in an ethical and compliant manner while building stronger relationships with the community. Karen Frascello will explain the basics of these unique programs and the key considerations for setting up a global early access programs for rare disease patients outside of the clinical trial environment.

Probably an area of interest, would be how to get the voice of the patient into the marketing department.
I have prepared a workshop called 'A perfect storm'
A perfect storm of forces is changing the face of rare diseases.
1. There is more attention from pharmaceutical companies, which means there is more attention on pharmaceutical companies and there is more attention to their operating procedures. Regulators assume a higher level of expertise than they experience with small biotech companies.
2. There is more transparency to the cost of these therapies, due to the sensationalism that media attention generates.
3. There is a lot more awareness within the patient community, which means the patients are a lot less likely to be passive observers of the process.

In response to this storm, I believe in three disciplines.
- Build a strong relationship with regulators
- Establish a value proposition
- Engage with patients to design and build the programme
Key points:
- Building a strong relationship with regulators.
- Rare disease does not mean unknown. A rare disease affects a small number of patients but there are many rare diseases and they are beginning to influence society.
- US regulators have granted 4000 Orphan Drug designations since the Orphan Drug Act in 1983
- As the number of new therapies increases, the path to approval is well trodden. There are so many special cases now, there is a change in attitude. Regulators are raising the hurdle for approval. Increasingly, more mainstream criteria are being applied, and the tests are more stringent.
- Establish a value proposition
- The very small numbers of patients has meant that both managed care settings and state funded health schemes accept higher prices. However worldwide sales of Orphan Drugs accounted for 16 % of drug revenues in 2016, with global sales of 114 billion Dollars. There is evidence that this tolerance might be re-examined.
- The developers of drugs are not necessarily small biotech companies. Today the players include large pharmaceutical companies who bring different criteria to drug development based on the economies of scale that come from high recruitment in common diseases. They struggle to learn the inefficiencies of small studies with low recruitment per site.
- Engage with patients to design and build the programme
- In the triangle of patient, drug and physician, the patient is no longer a silent partner who should be grateful that they are receiving attention.
- It is the voice of the patient that will guide development. Few of the new therapies will cure their target diseases, most will make life better. The criteria for development and the definition of success must be written in patient language.

This workshops draws on the experience of Karen Frascello having been involved in over 50 global access programs. The group will discuss the challenges for setting up and managing requests globally and share best practices for successful access programs.

Gulce will give an overview of Orphan Drug market in Turkey. She will talk about possible entry strategies for Orphan Drug companies and also involvement of patient organizations in the system.