Treatable, untreatable, undetermined: Overcoming rare disease

Manjinder Bains, Country Medical Director UK & Ireland at Ipsen, illuminates the underestimated impacts of rare and ultra-rare conditions
Pharmafile: What are some of the obstacles many patients face in the diagnosis of rare diseases?
Manjinder Bains: Many rare diseases will never be encountered by a clinician in their whole career. Because of this, awareness and understanding of specific rare diseases is generally low amongst the majority of healthcare professionals (HCPs). With as many as 7,000 known rare diseases, diverse and often-complex in nature, reaching a correct diagnosis can be a long and arduous journey. It is not uncommon for a diagnosis to take over five years, with some patients experiencing delays significantly longer.
Within this period of uncertainty, patients often face a myriad physical, practical, and mental health challenges. While clinicians will do their best to understand and manage the unexplained symptoms their patient is experiencing, a reality is that the person in question may not be receiving the treatment they need. The consequences of this can range from the worsening of their disease and symptoms to an increased likelihood of irreversible damage or even shorter life expectancy.
When an HCP does not see an improvement and the diagnosis remains elusive, the common solution is to seek greater expertise and refer patients elsewhere. In fact, in the UK, patients with a rare disease see, on average, eight clinicians, including four specialists, before a diagnosis. The patient and their family will have to deal with numerous appointments, tests, and misdiagnoses, which can severely impact the patient’s life – from missing school or time off work to being unable to cope with much else beyond their condition – often with no end point in sight.
We believe in the importance of supporting HCPs, and most importantly patients, to help overcome obstacles to rare disease diagnosis.
For the patient at the centre of these diagnostic pathways, the journey begins at symptom onset where their first port of call is most often their GP. While it is not feasible to expect a clinician to be familiar with even a fraction of the possible rare diseases, novel technological approaches can support GPs by flagging risk factors and symptom combinations that might be indicative of ultra-rare diseases. By partnering with health technology companies providing these services, Ipsen hopes to improve intervention at the earliest possible point in the diagnostic pathway.
Moving forward, the industry must work closely with the NHS, patient advocacy groups (PAGs), and patients to better define diagnostic pathways, leveraging research, real world data, and patient experience to optimise these processes.
The cause of many rare diseases is often unknown or not fully understood, as is the case for neuroendocrine tumours (NETs). What changes would research into identifying causes be able to bring about?
While the specific causes of many rare diseases remain undetermined, a significant number are known to result from genetic abnormalities. Over the past 20 years, huge advances in genomics and health technology have opened the door to new research possibilities, helping us to better understand risk factors associated with certain rare diseases and how their early presentation differs from patient to patient. We now need to bridge the gap between research and clinics, and support HCPs in spotting early manifestations of these conditions.
As a step towards this, Ipsen is working with health technology company Mendelian to equip clinicians with a tool to assist in the early detection of NETs. Mendelian’s MendelScan tool can flag patients that are suspected of having a rare disease, including suggesting investigation into NETs. The scanning algorithm does this by searching electronic health records for indicators of rare diseases and associated clinical patterns.
Genetic testing is also important, and not only plays a role in understanding the causes of rare disease, but can also be utilised in diagnostics. Last September, the UK Government set out a 10-year strategy to create the most advanced genomic healthcare system in the world, building on the success of the 100,000 Genome Project and the ongoing UK Biobank, amongst other genomic research programmes. As part of their plan, the government will aim to roll-out whole genome sequencing to patients with a suspected rare disease, which could be instrumental in achieving earlier diagnosis of these conditions.
What are the next steps to improve the standard of care given to patients with rare diseases, and what are some of the most significant hurdles on the way to meeting their needs?
Historically, small patient populations have presented cross-sectional challenges when it comes to rare disease, from difficulties in recruiting for clinical trials, to a lack of investment and limited patient voice. There have also been significant challenges in showing the value of therapies using conventional models of cost-effectiveness. However, changes to the way in which new drugs are tested and evaluated means the pharmaceutical industry has been able to better utilise real-world data and patient insight. This has helped to remove some of the barriers to bringing new therapies to market, and allowed us to generate important debate about the provision of care for those impacted by rare conditions.
While rare individually, collectively, rare diseases affect 1 in 17 people, meaning there is a massive community of people that could benefit from improved standard of care. This can often be achieved in a realistic and practical way: creating more specialist centres, increasing homecare provision, and providing more support for caregivers.
As with all disease areas, patient organisations play a crucial role in providing information and support to patients and their surrounding networks. At Ipsen, whenever possible, we partner with these dedicated groups to help raise vital awareness, and provide information and support to rare disease communities.
The effects of suffering a rare disease are far-reaching, extending beyond initial symptoms of a condition. What are some of the consequences of rare diseases often neglected in discussions of their impact?
While there are the obvious physical impacts of living with either a diagnosed or undiagnosed rare disease, there is also a huge psychological toll on the patient and their support network. Dealing with a disease diagnosis can be a confusing and daunting time, and while this is true for many conditions, emotions can be heightened with rare diseases. Unfortunately, due to the limited awareness of these conditions, there are often fewer resources and support services available to both the patient and their loved ones. Sadly, this has been exacerbated by COVID-19, which made people less able to connect with those around them and access external support.
Ultimately, the most important factor to consider is the quality of life attained by the patient living with the rare disease. Too often, the focus is only on whether treatment is reducing symptoms and prolonging life. However, the impact of treatment on the overall quality of life (QoL), and the ability for a patient to participate in work, socialising, and other aspects of their lives, should be considered as equally, if not more, important.
The changes being implemented by National Institute of Health and Care Excellence (NICE) to their health technology appraisals, following their recent methods review, are a positive step towards better factoring in QoL, when considering the value proposition of novel or innovative therapeutics.
How might certain rare diseases help us better understand medicine as a whole?
Rare diseases as a whole encompass a broad spectrum of therapy areas and affect a multitude of bodily systems, so there are often learnings from our research into rare diseases that can be applied more generally, providing insight on disease drivers, genetic predispositions, disease pathology and inheritance patterns. In particular, genomics is a fantastic tool for understanding disease and medicine, and we are now able to utilise the capabilities of technology to store this data and build an increasingly clearer picture of health and disease. While health technology software is currently being utilised to scan for rare diseases, as this bank of genomic data, along with stored clinical patterns and symptom presentations expands, it may become possible for these approaches to aid clinicians in the earlier diagnosis of more common diseases.
2021 marks the 15th Anniversary of the announcement of discovering the mutation ALK2/ACVR1 gene, which causes fibrodysplasia ossificans progressiva (FOP). Since 2006, what has changed in the management of the disease as a result of this?
The most important change is that there has simply been a much greater focus in the last 15 years on FOP as a disease. Prior to this, awareness and understanding of FOP was relatively low. This change is, of course, positive in terms of the impact on those patients living with FOP – ultimately more understanding of the disease and burden of illness leads to greater drive to investigate and develop treatments to improve outcomes.
The other key change that has happened is that the importance of early diagnosis has been brought to the forefront of FOP management. The fact that we now have a genetic marker to support that all-important diagnosis is crucial for many patients and their families.
There is currently no definitive treatment for FOP. Is this often the case with rare diseases, and what is needed to address it?
As with other therapy areas (and especially in the case of rare diseases) patientcentricity needs to be kept front of mind. It is understandable that rare disease patients may sometimes feel ‘forgotten about’ or ‘left behind’. A feeling of being alone is understandable when a patient may have never met anyone else with their condition.
There is also merit in mentioning the importance of creating a focus on rare diseases for policy makers. Any approval and reimbursement processes need to be agile and adaptable as, simply put, it is a challenge to demonstrate the value of rare disease therapies using conventional models of cost-effectiveness. I am pleased to say that these processes are adapting and making better use of real-world evidence and patient insights to demonstrate value.
The most important takeaway is the plight of truly understanding rare diseases, and the importance of improving outcomes for those that live with them – be that treatments, homecare, support with mental health, or anything else that affects their overall QoL.

Dr Manjinder Bains, is Medical Director at Ipsen for UK & Ireland.
Passionate for science, innovation, and making a difference. Before devoting his fulltime work to Ipsen, Manjinder has over 12 years pharmaceutical experience in both the UK and Switzerland, across four organisations in a range of roles within medical and commercial functions. Prior to joining the pharmaceutical industry, Manjinder spent almost nine years in the NHS as a trainee surgeon across a range of geographies.