“Eight out of 10 rare diseases have a genetic origin.”
Louise Fish, Chief Executive, Genetic Alliance UK
“Despite the challenges around us, there’s good reason for optimism.”
Craig Martin, CEO, Global Genes
Our study of the mental health of people affected by rare conditions – either as patients or those who care for them – showed that more than 9 of 10 of the survey respondents felt anxious or depressed, and several have had suicidal thoughts. Yet the majority had never been asked by healthcare professionals about their mental health.
Therelationship between specific rare conditions and mental health is complex and varied. Some conditions have neurological components causing atypical mood or behaviour. People may be living with the long-term impact of the condition, which might be progressive or life-shortening.
Others have physical symptoms which take a toll on mental health; these might be symptoms that change one’s appearance from what is considered normal or symptoms that make one less independent in everyday life, having to avoid being too far from a toilet, or one’s medicine or having to avoid sunlight. Of course, living with pain, whether it is chronic or episodic, is a burden that can damage one’s mental health.
A lot of this will sound familiar to those living with common-complex conditions, but rare conditions work as an amplifier to experiences or challenges.
diagnosis that we found was affecting mental health too.
Similarly, care coordination, where clinicians from a range of disciplines must coordinate to deliver optimum care is contributing to poor mental health. The burden of having to fill this gap, either as a patient or carer, where we see people having to step in and coordinate between clinics themselves, can create a negative spiral.
All of these experiences can be magnified again by a minority background, which can add an additional element of isolation, potentially worsening mental health outcomes further.
The burden of having to fill this gap, either as a patient or carer, where we see people having to step in and coordinate between clinics themselves, can create a negative spiral.
A further reason to deliver Mental health is a component of the overarching UK Rare Diseases Framework (2021), the five-year policy that commits to improving outcomes for people with rare conditions.
The events of the past couple of years have forced us all to think and act differently in many aspects of our lives. For those living with rare diseases this has long been the norm.
WRITTEN BY Craig Martin CEO, Global Genes
Sincethe start of the pandemic, we’ve come to appreciate the importance and urgency of innovation in facing critical health challenges. We’ve followed clinical trials and become educated in the underlying science in unprecedented ways. We’ve learned to recognise inequities in healthcare and have sought to become more inclusive.
Adapting during the pandemic Rare disease families have understood and struggled with these realities long before COVID-19.
equitable, global access to critical medicines.
A new era for the rare disease community “Despite the challenges around us, there’s good reason for optimism,” says Craig Martin, CEO of Global Genes. “We’re entering a new era in which rare disease communities – connected by shared purpose, technology and data – are playing a central role in driving impact across rare diseases, on a more equitable and global scale.”
Low awareness of rare conditions makes our community’s experiences less relatable and so sympathy, empathy and understanding are harder to find. A major contributing factor to poor mental health were issues specific to managing rare conditions in the health service. Slow diagnosis, symptoms being dismissed and the accusation that ‘it’s all in your head’ are all well-understood challenges around rare condition
There needs to be a focus on empowering healthcare professionals who treat rare disease patients and on the integration of mental health support with rare disease services. Improving the mental health of our community will be an added benefit of delivering the UK Rare Diseases Framework.
The pandemic has amplified challenges, with many patients experiencing constraints in access to critical medical procedures, trials, testing or treatments, as well as severe financial, mental health and wellness challenges.
As leaders, we have a responsibility to be informed, innovative and inclusive in how we work to enable progress across rare diseases.
Yet rare disease communities, used to responding in real-time to crises, have adapted with resiliency and nimbleness, working together to address issues and help those struggling or left behind.
The global crisis has also generated new opportunities and ways of connecting with potential positive implications for rare disease communities.
Global Genes has adjusted to anticipate changing dynamics and prepare patients, caregivers, and its Foundation Alliance of more than 800 rare disease groups, for what’s ahead. This includes launching a RARE Community Portal, which allows distinct communities to connect, convene and share information virtually around critical topics or initiatives.
WRITTEN BY Nick Meade Director of Policy, Rare Disease UKExamples of pandemic-driven progress include broadened access to telemedicine, virtual and adaptive trials, an increased emphasis on comprehensive testing, accelerated development of treatments and more
“As leaders, we have a responsibility to be informed, innovative and inclusive in how we work to enable progress across rare diseases,” states Martin. “We need tech to reach communities at scale, identify gaps, and find solutions. But we have to balance that with meaningful, personalised engagement, so we meet people where they are and ensure they’re equipped to take the best next steps forward.”
Senior Manager: Emma-Jean Director: Alex Williams Head of Business Development: Content Editor: Angelica Hackett O’Toole | Head of Digital: Harvey O’Donnell Paid Media Strategist: Jonni Asfaha Social & Web Henry Phillips Digital Assistant: Carolina Galbraith Duarte images supplied by Gettyimages, unless otherwise specified information: uk.info@mediaplanet.comEach person diagnosed with a rare disease has a unique experience and story to tell. However, with over 7,000 rare diseases currently identified, these patients collectively form a significant group that often has unmet needs.1
Recognising the experiences of these patients and those who care for them is essential in order to develop effective treatment and management options.
Although it is estimated that over 30 million people in Europe live with a rare disease, only 6% of these diseases currently have a treatment.2
Identifying and diagnosing patients is a critical challenge for healthcare systems.
Putting aside preconceptions
There are rare diseases which are more prevalent in one gender over another. However, when it comes to rare bleeding disorders, there is a common misconception that they only affect men. This means that many women with diseases such as haemophilia or von Willebrand disease remain undiagnosed while suffering from debilitating symptoms including pain, increased risk of heavy menstrual bleeding and higher risk of postpartum haemorrhage.3 Furthermore, the treatment needed by women with bleeding disorders as they go through life events such as puberty, pregnancy and menopause is highly personalised, depending on family history, severity and so on.3
30 million reasons to drive progress Improvements in access to treatments for rare diseases in recent decades gives us cause to celebrate. However, the reality is that millions of people across Europe still have unmet medical needs. The EURORDIS Rare 2030 survey on the future of rare disease, highlighted that access to treatments that are not yet available, as well as better coordination of healthcare are top priorities for patients.4
To support all people with bleeding disorders and other rare diseases, we need to innovate at pace, improve diagnostic and treatment facilities and ensure that new therapies get into the hands of patients who need them. Patients, health providers, researchers, industry and governments must all work together to drive multistakeholder dialogue and bring about positive policy change. This can only be done when we make patients our priority and put their stories at the centre.
References 1. Rare Disease Day. Frequently asked questions. Available at: https://rarediseases.org/wp-content/uploads/2019/01/RDDFAQ-2019.pdf Last accessed September 2022.
2. Parliamentary question. EU action plan on rare diseases. Available at: https://www.europarl.europa.eu/doceo/ document/O-9-2021-000069_EN.html. Last accessed September 2022.
3. European Haemophilia Consortium. Women with Bleeding Disorders. Available at: https://www.ehc.eu/bleedingdisorders/women-with-bleeding-disorders/. Last accessed September 2022.
4. EURORDIS. Rare disease patients’ opinion on the future of rare diseases. Available at: https://download2.eurordis.org/ rbv/rare2030survey/reports/RARE2030_survey_public_ report_en.pdf. Last accessed September 2022.
“The question is, what is a ‘fair price’ for an orphan drug that may not work or lose its effectiveness after five years or 10 years, etc?” asks Michel. “This is why new strategies must be used to define fair price.”
Rather than paying one large amount, Epstein explains that a ‘pay for performance’ model should be adopted with pricing adjusted as evidence of real-world effectiveness, safety and durability becomes available.
This article has been sponsored and approved by CSL Behring [GBR-CRP-0356/ September 2022].
A ‘pay for performance’ model should be adopted for rare disease drugs, with pricing adjusted as evidence of realworld effectiveness becomes available.
For instance, annual instalment payments could be made over five years, with lower payments in later years if a drug loses potency.
Europe, agencies that decide on reimbursement for drug development — such as NICE in the UK — want assurance that any new therapies will deliver good health value for patients and good monetary value for health systems.
“These agencies are dealing with public money,” says Susanne Michel, Head of HTA Evidence Strategy at Ascenian, a pricing and market access consultancy serving the pharmaceutical, biotechnology, medical devices and medical diagnostics industries. “It’s why they have strict evidence requirements and insist on seeing long-term data from drug trials featuring large numbers of patients.”
By the nature of rare conditions, patient numbers are low, which makes it difficult to design the type and length of trials sought by payers. “The US faces the same challenge,” explains Michael Epstein, Ascenian’s Head of Commercial Strategy and Pricing.
“The difference is that there isn’t one central agency, such as NICE. Instead, there are hundreds of private payers. But their concerns are the same: they want value for money.”
In Europe and the US, Michel and Epstein insist that new pricing and evidence assessment approaches are needed to speed the delivery of orphan drugs.
“New parameters of evidence should be established for orphan drugs,” says Michel. “Payers traditionally reject surrogate endpoints on methodological grounds and not accurately displaying the patient benefit, but there may be a good case to accept them for some orphan drugs — at least with other data combined to allow inferring the patient benefit.”
Pharma companies need to change their operations, too. “At the moment, reimbursement prices are negotiated once all trials are finished and all evidence is in,” says Michel. “Companies must engage in price and value potential assessment much earlier. Changes must be made — on both sides — so rare disease patients can have access to the drugs they need.”
Read more at ascenianconsulting.com
Paid for by Ascenian INTERVIEW WITH Susanne Michel Head of HTA Evidence Strategy, AscenianNew strategies must be used to define fair price for orphan drugsINTERVIEW WITH Michael Epstein Head of Commercial Strategy and Pricing, Ascenian WRITTEN BY Tony Greenway Paid for by CSL Behring WRITTEN BY Dr Karen Pinachyan Head of Medical Affairs Europe, CSL Behring Stormy who
To work in the rare disease space, pharma companies need to show commitment, flexibility and ingenuity, collaborate well and have a patient-centred focus.
Chandler, Head of Market Access UK and Ireland at global healthcare company
Sanofi, knows how vital it is to improve diagnosis times and treatment outcomes in rare diseases. Thirteen years ago, her son — now aged 16 — was diagnosed with Duchenne muscular dystrophy (DMD), a rare and fatal progressive disease.
“My professional and personal lives overlap,” says Fleur. “I remember trying to get a diagnosis for my son, but rare diseases diagnosis — 75% of which start in childhood1 — can take five years on average.2 Because of my background, I suspected DMD before it was diagnosed, but many people aren’t in that position. As a parent, I’m aware that waiting can be extremely draining because you know that something is wrong.”
Fleur welcomes the Government’s UK Rare Diseases Framework,3 published last year, which outlines four key commitments: quicker final diagnosis; increased awareness of rare diseases among healthcare professionals; better coordination of care; and improved access to specialist care, treatments and drugs.
These commitments align with the healthcare company’s rare diseases priorities. “We’re now focused on the tangible things that need to happen to make those commitments a reality,” says Ben Whitehouse, Head of Rare Diseases UK and Ireland at Sanofi. “For example, we believe AI, big data and machine learning are a key part of the future for rare diseases and can be used to reduce diagnosis times. We’re currently running a number of pilots using this technology and see an opportunity for algorithms to identify patients who are undiagnosed or misdiagnosed. ”
However, they know they can’t make these advances on their own. “That’s why we’re collaborating with several partners, including those who have expertise in the data space,” says Ben. “These partnerships also involve working closely with the NHS to ensure the best outcomes for patients.”
When it comes to developing new treatments, this is a field facing particular challenges. By their very nature, rare diseases don’t affect many people, which makes clinical trials difficult. But thanks to patients’ engagement, such trials are possible.
Ben admits that developing rare disease treatments can take years, which is why pharma companies like Sanofi must show commitment, ingenuity and flexibility. “For example, we’ve been investigating acid sphingomyelinase deficiency (ASMD), a rare, progressive and potentially lifethreatening disease, for two decades,” says Ben.
“We’ve kept going because we know how important it is for patients and their families.” Ben notes that they are particularly proficient at setting up registries to generate patient data. They demonstrate to funding agencies the difference that a particular treatment can make to those with a rare disease.
“We know, collaboration across patient organisations, industry, academia, decision-makers and clinicians is the key,” says Fleur. “That’s why we are in the process of setting up such groups, looking at evidence which is vital, such as quality of life in carers of those with rare life limiting diseases.”
Earlier this year, Ben took part in a choir event sponsored by Sanofi, called Pompe and Circumstance to raise awareness of Pompe disease, which can cause muscle weakness and breathing problems. Patients, patient advocacy groups, industry, physicians and nurses all gathered to record a song to coincide with International Pompe Day.
“It was genuinely the most moving day I’ve experienced in my 20 years in pharma,” says Ben. “Everyone was working together, even though many of us were out of our comfort zones. It shows what collaboration can achieve. That’s why I’m optimistic.”
“Pharma has a duty to all diseases,” says Fleur. “We want to enable rare disease patients and their families to be able to access innovative treatments and live as full a life as possible, and to experience joy wherever they can find it.”
References
1. The long journey to a rare disease diagnosis. Available from: https://ec.europa. eu/research-and-innovation/en/horizon-magazine/long-journey-rare-diseasediagnosis
2. The long journey to a rare disease diagnosis. Available from: https://ec.europa. eu/research-and-innovation/en/horizon-magazine/long-journey-rare-diseasediagnosis
3. The UK Rare Diseases Framework. Available from: https://www.gov.uk/ government/publications/uk-rare-diseases-framework
“We’ve kept going because we know how important it is for patients and their families.”INTERVIEW WITH Ben Whitehouse Head of Rare Diseases UK, Sanofi INTERVIEW WITH Fleur Chandler Head of Market Access UK and Ireland, Sanofi WRITTEN BY Tony Greenway
care can only happen after the right diagnosis is made. Also, finding patients earlier helps eliminate some of the costs associated with delay in diagnosis and saves GPs time. This technology is not there to replace clinicians. Clinical reasoning is sovereign. It’s there to support them and make their job easier.
How does the technology work?
LvW: It sifts through data and alerts doctors that there is a patient in their practice who has an elevated risk of rare disease. Those doctors then receive accurate background information about the disease and the standard practice for diagnosis which helps them make better decisions. It’s important to say that the technology is applied to the data — we don’t see the data. We never know who the patients are or even extract patient-identifiable information, so anonymity is always kept. The decision about what to do with the information is up to the doctor.
Algorithms can scan through anonymous patient data to help clinicians to discover those who may be at risk of having a rare disease. It could significantly speed up the diagnostic process.
Christopher Rudolf, Founder and CEO, Volv Global SA: Finding patients with rare diseases is like looking for a tiny constellation among thousands of stars. To put the problem in perspective: there are vastly more data points in a patient record than there are visible stars in a clear night sky. We’re asking doctors to look through all that data to find a disease — or, in our analogy, scan the skies to spot a ‘constellation’ — that they may never have even heard of. That’s not humanly possible. It can only be done with AI technology.
What are the benefits of early diagnosis?
CR: People living with a rare disease are diagnosed seven years too late, on average. Take Fabry disease and Pompe disease. People with Pompe disease can wait up to 12 years before they receive a diagnosis, and Fabry disease patients can wait even longer. Sanofi is supporting us to discover patterns for both diseases using
complex but accurate algorithms so that patients can receive a much earlier diagnosis.
What is meant by an ‘earlier’ diagnosis?
CR: For example, in the USA, we can use algorithms to find patients with a disease called Alpha-1-antitrypsin deficiency, or AATD, two years earlier than a clinician would typically be able to. In the UK, we think we can find some Fabry and Pompe disease patients even earlier. It’s only possible now due to the amount of data — and I stress this data is anonymous to us — that is available in GPs’ patient health records.
What is the difference to patients and clinicians?
Léon van Wouwe, Clinical Innovation Director, Volv Global SA: When people living with disease get a diagnosis, they can start to make informed choices that reduce the impact that the disease has on them, their families, friends, carers and even work. After all, access to tailored
How accurate is the technology?
LvW: A doctor has validated our model with a review, so we are confident that our performance for Pompe has an 80% precision of plausible people that should be tested for the disease; and for Fabry it’s 88%.* Avoiding getting it wrong must be the priority because doctors and nurses must be able to trust the performance of the technology, and — critically — we don’t want to distress patients with a misdiagnosis. Apart from worrying them unnecessarily, it can put them on a therapy path not tailored to their disease.
Can this technology be used for all rare diseases?
CR: Many rare diseases can be screened for at birth, so it’s not necessary. Some rare diseases are obvious after the onset of symptoms. This technology focuses on diseases that are incredibly difficult to diagnose. The challenge is to constantly improve it and think of other ways to discover all the other disease ‘constellations’ in our night skies.
INTERVIEW WITH Christopher Rudolf Founder & CEO, Volv Global SA INTERVIEW WITH Léon van Wouwe Clinical Innovation Director, Volv Global SA WRITTEN BY Tony GreenwayThis technology is not there to replace clinicians. It’s there to support them and make their job easier.
History was made at the United Nations (UN) with the adoption of a General Assembly Resolution on “persons living with a rare disease and their families.”
Advocating for the right to health
WRITTEN BY Flaminia Macchia Executive Director, Rare Diseases International (RDI)
Civil society groups are now turning their attention to how this groundbreaking text can help transform care for rare diseases. In recent years, Persons Living with a Rare Disease (PLWRD) have gone from being near invisible to the UN and international institutions to gaining increased recognition as a vulnerable population requiring attention. This transition is reflected in the UN resolution, which was adopted by consensus by all UN member states last year, as well as the inclusion of rare diseases in the UN political declaration on Universal Health Coverage (UHC).
However, without specific policy frameworks and support, health systems and governments are unable to implement international commitments. Over 300 million PLWRD worldwide cannot fully realise the right to health and experience significant difficulties receiving a diagnosis and accessing treatment, services, and appropriate care.
Universal Health Coverage for rare diseases
Rare disease groups, led by Rare Diseases International (RDI), are working together toward the implementation of the UN resolution. They are currently advocating for the integration of rare diseases in national and international policies aimed at achieving Universal Health Coverage and strengthening health systems.
We need specific frameworks and actions to advance UHC
to prioritise rare diseases. The community’s message to policymakers is that Universal Health Coverage cannot be achieved unless and until health systems address the needs of Persons Living with a Rare Disease.
Connecting experts globally
At the margins of the World Health Assembly in May, World Health Organization (WHO) Director of Health Promotion Rüdiger Krech announced the launch of a collaboration with RDI toward the establishment of a global network of expertise to collaborate on rare diseases.
The network, which is in the development stage, would link centres of excellence, clinics, and experts around the world and pool resources to enhance the accessibility and quality of diagnosis and care.
The WHO representative said the network’s vision would be to ensure people are diagnosed earlier and medical professionals receive proper counselling and advice through global support in order to improve care for PLWRD.
Toward a WHO Resolution
Together with the development of the network, RDI is advocating for a WHO Resolution on Universal Health Coverage for rare diseases to ensure all people, regardless of where they live, have access to timely diagnosis and care.
We need specific frameworks and actions to advance UHC to prioritise rare diseases.
For a majority of the estimated 300 – 400 million patients worldwide living with a rare disease, 2 the challenge begins with the diagnostic process, which can sometimes last decades. This equates to over 3.5 million people in the UK.3
Toreduce the diagnostic and treatment delay that exists for many rare diseases, education is crucial.
These patients are bounced between multiple primary care practitioners and various specialists to undergo tests and seek answers. Often, no one clinician can put the pieces together to confirm a diagnosis. This can place a large burden on healthcare systems as patients go through batteries of tests that may be invasive and/or unnecessary, only for the patient to receive a delayed diagnosis or even an incorrect one leading to late and/ or harmful treatment. This may then result in disease progression and potentially irreversible organ damage.
A destination for learners
As part of an initiative to improve access to education for rare disease diagnosis and management, Medscape Education created a dedicated learning centre. It houses more than 125 educational activities and is collaborating with medical societies, patient advocacy groups, and other organisations to provide access to disease-specific and general rare disease resources and information.
“The millions of people who live with a rare disease may feel isolated, but they share a common goal of needing a diagnosis and proper management of their disease. We are ideally positioned to reach clinicians with the education they need due to our vast membership and the trust clinicians have in us, and that is why we established this learning centre. There are a variety of useful resources available, all with the goal of reducing the delay in diagnosis and increasing awareness of available treatments,” says Dr Hansa Bhargava, Medscape Education CMO.
Scientific developments underway The future of rare disease diagnosis and management has its bright spots and continuing challenges. An astonishing 95% of rare diseases have no treatments.4 However, progress is being made in terms of new therapies being approved by regulatory bodies; and orphan designations and priority/fast-track reviews, as well as government incentives, are helping to increase the number of treatments every year.
WRITTEN BY S. Christy RohaniMontez PHD Director, Clinical Strategy,
Clinician education can help combat the challenges of rare disease diagnosis and management. A stark reality of the situation is that many clinicians do not think they see rare diseases enough to be able to recognise them. In a survey of 978 clinicians across 16 different specialities taken by Medscape Education, it was shown that the prevalence of rare diseases is vastly underestimated.
Most clinicians said they only see patients with rare diseases once or twice a year, and only 20% feel confident in making a rare disease diagnosis.3 But those who have participated in Medscape rare disease education have significantly increased their knowledge and competence in diagnosis and treatment and have reported that they will make changes in their practice based on their learnings.
Because about 80% of rare diseases are associated with a genetic mutation,5 gene therapy is a possible therapeutic avenue in many cases. It’s been a slow road, but gene therapy technology advances have skyrocketed, and access to and the cost of genetic testing has eased, which is enabling earlier detection of rare diseases and potentially curative treatments. Even more compelling for earlier and more specific diagnoses will be the combination of information that may include genetic markers and other disease markers, as well as the use of AI-based algorithms.
Dr Bhargava adds: “We are on the cusp of a plethora of new diagnostic and therapeutic approaches that will revolutionise the field of rare diseases, and it will be exciting to see where we go next.”
References
1. Wakap SN, Lambert DM, Olry A, et al. Estimating cumulative point prevalence of rare diseases: analysis of the Orphanet database. Eur J Human Genetics. 2020;28:165-173
2. gov.uk/government/publications/uk-rare-diseasesframework/the-uk-rare-diseases-framework
3. Rohani-Montez SC, Bomberger J. Molecular Therapy Vol 30 No 4S1, April 2022: 255
4. https://www.thelancet.com/journals/landia/article/ PIIS2213-8587(19)30006-3/fulltext
5. https://www.frontiersin.org/research-topics/16513/ improving-medical-diagnosis-in-rare-diseases
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Around 3.5 million people are living with rare, genetic and undiagnosed conditions in the UK. Their voices must be heard loud and clear when strategic directions and priorities for rare diseases are being set by policymakers.
While rare, genetic and undiagnosed conditions are individually rare, around 3.5 million people living with these conditions in the UK.
Individually rare, collectively common
WRITTEN BY Louise Fish Chief Executive, Genetic Alliance UK
Eight out of 10 rare diseases have a genetic origin. The most common genetic conditions such as sickle cell disease affect around 15,000 people in the UK, with around 300 babies born with the condition each year.
Some genetic conditions affect just one family in the UK and a handful of people across the globe. Each year, around 6,000 children are born in the UK with a genetic condition so rare that it does not have a name because there is no test to diagnose it, or the genetic cause has not been discovered yet (known as a ‘syndrome without a name’ or SWAN).
better coordination of care, increasing awareness among health and care professionals and improving access to treatments and care.
Genetic Alliance UK makes sure that the voices of people living with rare, genetic and undiagnosed conditions are heard in the development of each individual Rare Disease Framework action plan for England, Scotland, Wales and Northern Ireland.
When someone is born with a lifelong rare, genetic or undiagnosed condition, they and their family need excellent care and support throughout their lifetime.
Genetic Alliance UK plays a vital role in championing the voices of 3.5 million people living with genetic, rare and undiagnosed conditions in the UK, their families and the amazing charities and support groups that advocate for them.
We are driving delivery of the commitments in the Government’s UK Rare Diseases Framework 2021 that set out how the lives of people with rare conditions can be improved over the next five years. The framework focuses on four key priorities to transform lives: faster diagnosis,
We also ensure these same voices are shaping the development of NHS England’s NHS Genomics Strategy, which will set the strategic direction and priorities for genomics over the next three to five years. Scientific breakthroughs have the potential to be transformative, but only if discoveries in the lab lead directly to practical improvements in diagnosis, treatment and care for individuals and families living with genetic conditions.
When someone is born with a life-long rare, genetic or undiagnosed condition, they and their family need excellent care and support throughout their lifetime.
Genetic Alliance UK is determined to transform the care provided to 3.5 million people in the UK so they can live their lives to the fullest.
At Alexion, our mission is to transform the lives of people affected by rare diseases and devastating conditions through the development and delivery of innovative medicines, as well as through supportive technologies and healthcare services. alexion.com/worldwide/UK
Living with a rare disease can be particularly challenging; from getting the right diagnosis to finding and accessing treatment that works.
It’s estimated there are around 7,000 rare diseases, and only 10% have treatments available. This means that most people living with a rare disease — defined by the NHS as a long-term debilitating condition affecting less than five or fewer people in 10,000 — may have no treatment options. Even if potential treatments exist somewhere in the world, they may not currently be accessible for patients in many countries, if ever at all.
Although it might seem overwhelming for patients who are used to getting a prescription from their doctor to seek out innovative treatments, there are processes in place to help people with rare diseases gain access to new, investigational medicines.
John Lagus, EVP of Business Development at Tanner Pharma explains: “There are three main routes available to access a medicine: you can become part of a clinical trial, or if you are lucky, that medicine may be available commercially where you live. If neither of these is an option, most countries have legislations in place that allow patients, under the care of their doctor, to have an unlicensed medicine imported for use when that patient has no other treatment options.”
The benefits to patients of being able to access investigational medicines in this way are obvious in terms of the lifesaving or life-enhancing impact.
People living with a rare disease, their parents or carers, are often well-informed about their condition and what treatments are available, Lagus says. They are active advocates for their own rare conditions and are engaged with patient groups. This knowledge is increasing all the time as information about rare diseases becomes more widely available. Similarly, information about early access pathways is gaining awareness among rare disease patients and advocates.
Lagus adds that the best thing people with rare diseases can do is to engage with patient groups and their doctors. “Since accessing medicines for rare diseases is a physiciandriven process, the more information the patient has about procedures in their country, the better the outcome — even if it means they have to start the conversation with their doctor.”
If you are a patient who needs access to unlicensed medicine, speak with your doctor to see if early access is an option for you.
Over half of rare disease patients wait over two years for their diagnosis, with half of all patients receiving at least one misdiagnosis.
Arare disease is not just life-changing for patients but also their families and loved ones. For more than 30 years, patients and families affected by rare diseases have been our inspiration.
At Alexion, our research includes the translation of the complex biology of the complement system into transformative medicines. We remain committed to helping find new therapies for rare disease patients.
We support the publication of the Government’s UK Rare Disease Framework (January 2021), prioritising increased awareness of rare diseases, use of genomic testing and digital tools to support quicker diagnosis and better patient care. We look forward to the implementation of the national action plan.
Raising awareness of rare diseases among healthcare professionals can improve the speed and accuracy of diagnoses. We must ensure they can signpost patients to specialist support and care pathways.
For the 3.5 million people living in the UK with a rare condition, the ‘diagnostic odyssey’ of multiple referrals and inconclusive tests remains a reality. A 2020 survey led by Genetic Alliance UK, supported by Alexion UK, found that patients continue to be dissatisfied with the time to diagnosis. Among those without a definitive diagnosis, 61% had been searching for a diagnosis for over five years.1
The increasing use of digital tools and real-world evidence has the potential to improve diagnostic timescales, identify potential groups of patients and help GPs prioritise which patients need further investigation.
Research initiatives like the 100,000 Genomes Project, launched by Genomics England in 2012, have successfully sequenced 100,000 genomes from NHS patients affected by rare diseases or cancer. With more than 80% of rare diseases being genetic,2 the creation of a genetic library to define them led to groundbreaking insights. The first results of the project (published in 2021) found that 25% of participants received a new diagnosis thanks to whole genome sequencing.3
Improvements for rare disease patients can only happen if the whole system works together. We look forward to the rollout of the Rare Disease Action Plan and continue to work with various stakeholders to drive meaningful change for patients.
1. Alexion. Reforming Rare Diseases. December 2020. Available at: https:// rareexperience2020.geneticalliance.org.uk/wp-content/uploads/2020/12/ReformingRare-Diseases.pdf. Last accessed September 2022.
2. Genomics England. What We Know About Rare Diseases. Available at: https://www. genomicsengland.co.uk/genomic-medicine/understanding-genomics/rare-diseasegenomics. Last accessed September 2022.
3. 100,000 Genomes Pilot on Rare-Disease Diagnosis in Health Care — Preliminary Report. N England J Med 2021; 385:1868—1880.
Date of preparation: September 2022 Document Number: UK/NP/0112
Find out more at alexion.com/ worldwide/UK
INTERVIEW WITH John Lagus Executive Vice President of Business Development, Tanner Pharma WRITTEN BY Judith Ozkan Find out more at tannerpharma.com Paid for by Tanner Pharma WRITTEN BY RichardsonAnestimated two million people are living with a rare disease in Ukraine. Many of the 6,000 rare conditions are often disabling and frequently lifethreatening, even in normal times. When faced with a war, it adds an extra layer of complexity and uncertainty.
Since February 2022, EURODIS-Rare Diseases Europe has mobilised the wider rare disease community to help Ukrainians living with rare diseases because the community we serve is as vulnerable as it gets. How can someone with a rare skin condition survive in a basement while hiding from missiles without the risk of catching an infection? How can someone needing mandatory daily inhalations survive in a city that is cut off from electricity for months? And is there a way to flee the war if you are wheelchair-bound?
The Rare Barometer survey on Ukraine results shows that nearly 40% of Ukrainian families living with a rare disease were forced to move internally or abroad. At least eight in ten reported at least one interruption of the care they usually receive. Satisfying basic needs — a place to live,
food, water, hygiene products and clothing — is also an issue for many.
Various organisations and governments across the globe have mobilised their resources to support Ukrainians living with a rare disease, and a lot has been achieved, but there is more to be done. The humanitarian consequences of the war will remain in place for years to come. While our task is to cover the most urgent needs, we should also consider longer-term priorities, which require more sustainable solutions.
How to help those affected
We encourage international actors to proactively include Ukrainians living with a rare disease in their response programmes and take their complex needs into account — from accessible housing to adjusted employment opportunities to expensive treatments. After all, supporting the most vulnerable is our common mission.
We should not feel helpless. Everyone can do something to help those in need — by welcoming them, providing essentials or advocating for policies that facilitate their displacement. Let’s unite, leaving no Ukrainian with a rare disease behind.
More info at eurordis.org/ rare-barometer/ english/
MedicineR&D is difficult and takes a long time. With licensed medicines only available for around 500 of the 7,000 rare diseases, turning ideas into treatments for rare and ultra-rare diseases is even harder because of the lack of funding and the complexity of understanding rare diseases with limited patient numbers.
Self-funding medical research charity LifeArc is finding ways to change that, helping researchers overcome research challenges and get treatments to patients faster.
the lives of patients with diseases that are debilitating or life-shortening with limited treatment options,” says Crombie.
“But a big barrier for academics is how to develop them to a point that they can start trials in patients. These are highly complicated treatments and academics can find it difficult to get access to the specialist facilities, materials, manufacturing processes and the expertise that can ensure the treatments can be used in a clinical trial,” Crombie adds.
WRITTEN BY Mark Nicholls“We are providing advice, funding and science to help turn promising research into potential treatments,” says Dr Catriona Crombie, Head of the Philanthropic Fund at LifeArc.
The Philanthropic Fund awards grants to academics with promising projects focused on treatments, devices and diagnostics that could support people living with rare diseases.
Dr Crombie says: “To date the fund has awarded, over £9 million to research looking at 33 rare disease indications, exploring all kinds of approaches from cutting edge gene therapy, through to the use of antibodies or repurposing existing medicines.”
“New classes of highly specialised medicines, including gene and cell therapies, offer huge potential to transform
To address the challenge, LifeArc and the Medical Research Council (MRC), with support from the Biotechnology Sciences Research Council (BBSRC), announced an £18 million investment to create a national network of innovation hubs for gene therapies.
Medicines repurposing — where a medicine used or in development for one condition is researched for another condition — offers exciting potential for treating rare diseases. But it is not an easy route, and aspects like intellectual property or the format of the medicine can create challenges.
“We have partnered with The Medical Research Council to create a repurposing medicines toolkit. It’s a free, online resource to help researchers, charities and others navigate the complex path to patient access for repurposed medicines,” Crombie explains.
LifeArc has scientific research facilities in Stevenage and Edinburgh and a specialist science team at the Francis Crick Institute in London. They have committed to invest over £1 billion by 2030 to make life science life changing and will be launching further initiatives to support rare disease translational research.
Find out more at lifearc.org
How can someone with a rare skin condition survive in a basement while hiding from missiles without the risk of catching an infection?Senior Project Manager for Ukraine Response, EURORDIS-Rare Diseases Europe Ukrainians with rare diseases often rely on luck to live. Even those with debilitating symptoms and limited mobility with the most urgent needs are unable to access essentials. by INTERVIEW WITH Catriona Crombie Associate Director, Technology Transfer, LifeArc
We aim to support academics, charitable organisations and other institutions to transform their ideas into tangible solutions.
Greater patient engagement in rare disease drug trials is not just a ‘nice to have.’
NaomiLitchfield, Global Patient Advocacy Lead at contract research organisation Bionical Emas, who specialise in facilitating clinical development of new treatments for rare diseases, says: “Positive patient engagement is a crucial part of the drug development process.”
As a former Senior Clinical Research Nurse at Great Ormond Street Hospital, Naomi cared for rare disease patients participating in clinical trials and early access programmes and has seen the impact investigational drugs can have. Now, she and her team are enabling partnerships between pharmaceutical companies and patient advocacy groups throughout the drug development process.
“Patient engagement must be early, often, and transparent,” says Naomi.
The process starts at the drug development preclinical stage, with the creation of an access policy and a patient communication plan.
“Companies need to understand the patient’s condition, and that means listening,” she says. Naomi and her team create materials to support the patients, from education materials about clinical trials and early access programmes to communication templates and frequently asked questions documents.
At the clinical development stage, the team looks to reduce patient burden as much as possible.
Considering the patient perspective early in clinical development supports the choice of clinically meaningful endpoints, which can be particularly challenging in rare diseases.
Patient engagement with payers such as the NHS or health insurers can also be really valuable. A clear understanding of patients’ needs here can create efficiencies and accelerate timelines — especially important in rare diseases,” says Naomi. “Many are progressive and hard to diagnose, so after a long diagnostic journey, patients and families may not have much time.”
Once a new drug is commercialised, the team helps plan communications — where their relationships with patient groups can help — and provides feedback from trial participants for future clinical development. “Feedback to patients is also vital,” she says. “Many take part in clinical trials; not just for early access to new treatments but to help future generations. Positive patient engagement benefits all parties.”
Like many others, patients with hypoparathyroidism around the UK are now experiencing difficulties accessing the essential medication that keeps them alive.
Hypoparathyroidism is rare, serious and affects all ages. Insufficient parathyroid hormone leads to low calcium levels in the blood which cause distressing symptoms and, without treatment, can be fatal.
It is a challenging condition to manage as there is no readily available replacement parathyroid hormone. Treatment relies on high-dose One Alpha (alfacalcidol) — an oral active vitamin D.
Patients around the UK are having difficulty accessing their essential medication.
Switching brands often destabilises calcium levels leading to urgent hospital admissions and restoring stability can take several months.
One of the 2022 key priorities of the UK Rare Disease Framework Action Plan is ‘improving access to specialist care, treatment and drugs.’ Instead, we are seeing the withdrawal of existing medication.
Parathyroid UK and their medical advisers have recommended immediate action to the DHSC and called upon the Society for Endocrinology to highlight the matter to its members. Hypoparathyroidism should be recognised as a rare condition requiring protected access to essential medicines for patients with this condition.
This medication needs to be added to the Medicines Repurposing Programme. We need a secure supply and the NHS is ideally positioned to make these drugs for itself.
In the long term, new ways to prevent and treat the condition and access drugs are needed. Cases are likely to rise as thyroid operations (currently 10,000 pa) increase, so efforts to optimise surgical outcomes and reduce the risk of post-surgical hypoparathyroidism are crucial and include restricting work to key centres, improving surgical techniques and adopting new intraoperative technologies.
Parathyroid UK is involved in a UK-wide multicentre trial (the NIFTy trial) of one such technology and awaits a new device being tested in a clinical setting that will allow patients to check their calcium blood levels at home.
Research takes time and requires funding. In the meantime, patients who are already struggling to manage a rare and underserved condition find themselves more at risk.
Over recent years, there has been an increased level of research and development into the rare genetic condition hereditary angioedema (HAE).
As a result of heightened research, there are more HAE treatment options available that can help to both prevent and control the disorder.
The severity of HAE
“People with HAE are prone to attacks of painful swellings in the skin or mucous membranes, which can affect the limbs, face, abdominal areas and throat.
Untreated swellings of the throat can be life-threatening,” explains Luke Robinson, General Manager UK, Ireland and Nordics at BioCryst Pharmaceuticals, a biotech company that is addressing unmet needs of people with rare diseases.
One of the challenges of HAE is its unpredictability. “Attacks can be triggered by an injury or infection, surgery, dental treatment, certain medicines, pregnancy and stress,” says Robinson. “Where there is no apparent cause, it could be triggered by stress or anxiety.”
International guidelines recommend that patients are assessed at every visit to identify the most suitable course of treatment.
HAE is a lifelong condition, but there are treatments. For acute attacks, patients are given subcutaneous injections, or — if that fails — intravenous therapy. Some patients carry the medicines with them and are trained to self-administer, but people who have frequent attacks may qualify for prophylactic treatment.
The mainstays of an effective acute or prophylactic treatment include factors such as ease of administration, speed of resolution of swellings and the degree to which attacks are prevented or reduced in severity.
Robinson says: “For patients, an effective treatment plan means better control of the unpredictable nature of HAE which could improve their quality of life — physically, mentally and emotionally.”
“BioCryst is committed to supporting people living with rare diseases, including HAE, by helping them manage the obstacles they face in their day-to-day life.”
Inviting patients as equal partners in the drug development process
Lack of treatment solutions intensifies problems for hypoparathyroidism
New HAE guidelines set more advanced standards for patientsINTERVIEW WITH Naomi Litchfield WRITTEN BY Linda Whitney
WRITTEN BY Professor William D Fraser Professor of Medicine, Norwich
SchoolINTERVIEW WITH Luke Robinson General Manager, UK, Ireland, Nordics & Head of EU Marketing, BioCryst Pharmaceuticals, Inc. WRITTEN BY Linda Whitney
Bysupporting small drug firms to navigate the licencing process to the wider marketplace after regulatory approval has been granted, logistics firms are helping innovative drug developers with significant cost savings in the process.
According to healthcare logistics expert Richard Lunney, this means patients with rare conditions benefit, while niche drug development companies can invest in further products.
He explains that to gain a WDA, drug companies need premises, a quality management system and qualified staff and then apply to the MHRA (Medicines and Healthcare products Regulatory Agency) for the licence to sell their product on the market.
Therismos already has that infrastructure in place, with expertise across several health sectors, meaning companies can outsource this aspect of the drug marketing process.
WRITTEN BY Richard Lunney Managing Director, Therismos LimitedDrug manufacturers must secure a Wholesale Distribution Licence — also known as a WDA (Wholesale Distribution Authorisation) — before new drugs can be distributed to patients.
Traditionally, companies acquire it themselves, which may take up to nine months. Or — they strike a licencing deal with another organisation but lose ownership of the product.
A third, lesser-known, route is via a specialist distribution company, which can support smaller companies — that may have tighter cash flow — in the process, and thus facilitate patient access to groundbreaking medicines for rare diseases.
Consequently, companies do not have to secure a WDA themselves or have the associated staff and time costs. Instead, they can focus on securing regulatory approval and refining the product before formally engaging Therismos in the weeks before the product goes to market.
The general cost saving is about 80%, releasing funds to be reinvested by the Innovator. Outsourcing the process also limits the risks of delays in product launches.
Paid for by Therismos LimitedLunney is managing director of Therismos Pharma, a distribution partner providing pre-wholesale services to innovative biotech companies across the UK and Europe.
“What we are trying to do is keep that cost as low as possible so these companies can continue to reinvest in the development of new gene therapy or specialist products while getting access to the market,” continues Lunney.
“It’s a quick service. We can go from initial contracting to having the product in the UK in about eight weeks, which is good for patient access to these drugs.”
Therismos provides bespoke solutions to ensure companies retain ownership and control of their product distribution through hospitals, pharmacies and patients without the investment in owning and operating specialist licences.
We’re entering a new era in which rare disease communities – connected by shared purpose, technology and data – are playing a central role in driving impact across rare diseases, on a more equitable and global scale.
~Craig Martin, CEO, Global GenesPartnerships between niche drug companies and healthcare supply organisations are speeding up the process of getting essential drugs to patients with rare diseases.