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Rare Disease Day – looking to the future with hope

On this year’s Rare Disease Day, Amanda Henkel, VP, Strategy, Nucleus X Consulting (part of Nucleus Global), reflects on recent advances in the rare disease setting.

From the mother who spends hours at a clinical study site while her 3-year-old daughter receives an experimental treatment for spinal muscular atrophy, resolutely hopeful that she will someday be able to walk, to the occupational therapist spending weeks with a teenage boy with retinitis pigmentosa, helping him learn how to navigate the world when his sight finally goes completely – the annual Rare Disease Day (https://www.rarediseaseday.org/), held on 28 February, is a key date in the calendar for everyone affected by a rare disease. It has the ambitious aim of raising awareness among multiple stakeholders (including healthcare professionals, policymakers, industry and the public) of conditions so rare that few will have heard of them. Only with increased awareness can we catalyse change for the patients, families and carers around the world who are impacted.

Despite the profound impacts of COVID-19 seen far and wide across all areas of healthcare over the last 2 years, we’ve continued learning – and progress in rare disease has continued in leaps and bounds. So, as we mark this year’s Rare Disease Day, it’s a good opportunity to reflect on the recent advances that bring hope for the future.

Collaboration

Progress would not be possible without collaboration at all stages in the commercialisation of rare disease drugs, from clinical development to product launch, to those working hard to elevate the patient voice and drive legislative change. Central to this is the involvement of patient advocacy groups, patients and caregivers – who are relentless in their quest to ensure no patient goes unheard. And those voices are heard; since last year’s Rare Disease Day, a search of PubMed yields more than 25,000 new articles on rare disease. This is perhaps not surprising: while the prevalence of each rare disease is low, their aggregate impact is similar to, or greater than, many disease areas (including diabetes, breast cancer and Alzheimer’s disease).

The interest from the pharmaceutical industry is also significant. Orphan drug sales are expected to account for approximately 20% of US drug sales by 2024, and the non-profit organisation Global Genes’ upcoming NEXT 2022 report highlights the growing interest and investor confidence in rare disease drug development; a total of $22.9 billion was raised through public and private equity and debt financings in 2021, a 28% increase over the $18 billion raised in 2020. However, challenges in the commercialisation of rare disease treatments persist. In an ongoing effort to address these challenges, the Rare Disease Company Coalition (https://www.rarecoalition.com/) was launched ­in 2021. The Coalition represents an international group of life science companies (with 225 rare disease development programmes in progress) that are committed to discovering, developing and delivering rare disease treatments. Their goal is to inform and educate policymakers on the unique considerations faced when developing and bringing a drug to market.

In addition to pharmaceutical company involvement, several advocacy groups are also driving clinical research and the development of technologies such as gene therapy, gene editing and antisense oligonucleotides. The non-profit organisation Cure Rare Disease (https://www.cureraredisease.org/) is one such example. Founded by Rich Horgan, whose brother suffers from Duchenne muscular dystrophy, its goal is to develop customised therapies to treat patients with rare genetic conditions.

Empowering patients

Empowered patients can inform better and more effective trial design, ensuring that R&D programmes provide results that bring value to patients, enable a greater patient (and site) experience, and ultimately bring innovative treatments to patients faster. The DevelopAKUre consortium, a European collaboration involving academia, industry and patient organisations, demonstrated this recently when they partnered to accelerate the development of a treatment for alkaptonuria – a rare disorder caused by a genetic deficiency in an enzyme involved in tyrosine metabolism, which results in a build-up of homogentisic acid, manifesting in ‘black urine’ (Orphanet Journal of Rare Diseases). Their position statement provides recommendations to support best practice, including preparation, building a consortium, funding, and patient recruitment and retention. Key to their success was equal partnership between all members of the consortium and the central role of the patient organisation, which ensured the needs of the clinical study participants were met in real-time, which not only accelerated enrolment but also led to a high retention rate.

Early diagnosis and new technologies

Shortening the diagnostic journey is a major focus of advocacy groups; a correct diagnosis can take 6–8 years for some rare diseases and involves visits to multiple physicians. The International Rare Diseases Research Consortium (IRDiRC), a joint initiative of the European Commission and the US National Institutes of Health, is committed to ensuring that each patient with a suspected rare disease is diagnosed and receives care and available treatment within a year (if their disease is known in the medical literature). One of IRDiRC’s goals is to stimulate the development and approval of 1,000 new therapies for rare diseases by 2027. They appear well on their way to achieving this, with the first steps in their progress (a strategic gap analysis of the rare disease drug development landscape and creation of strategic themes to advance their goal) recently published in the Rare Disease and Orphan Drugs Journal.

Technology is being leveraged across healthcare – from the pandemic-driven access to telemedicine, remote monitoring and implementation of virtual trials, to informatics, artificial intelligence (AI) and machine learning – and can influence diagnosis and lead to improvements that might have a real benefit to patients’ lives outside of a clinical setting. Advances in this field are significant, and too broad to cover in this article, but a few examples stand out. In 2021, the FDA-funded Rare Disease Cures Accelerator-Data and Analytics Platform (RDCA-DAP®) initiative was launched, providing a centralised and standardised base to host and share de-identified rare disease data and support treatment innovation. RDCA-DAP promotes the sharing of existing patient-level data and encourages the standardisation of new data collection to accelerate the understanding of disease progression (including sources of variability to optimise the characterisation of subpopulations), clinical outcome measures and biomarkers, and facilitate the development of mathematical models of disease and innovative clinical trial design.

Recent advances in genome sequencing have shown the value of data analytics. A pilot study of 4,660 participants published in New Engl J Med (UK 100,000 Genomes Project) highlights the effect of whole genome sequencing on the genetic diagnosis of rare diseases. The study demonstrated an increase in diagnostic yield across rare diseases, with immediate clinical actionability in 25% of those who received a genetic diagnosis.

Two recent publications also illustrate the exciting potential for AI algorithms in supporting diagnosis. The first study, assessing 179 previously diagnosed paediatric cases from six academic medical centres (De La Vega et al. 2021), examined the diagnostic performance of an AI-based gene prioritisation tool (the Fabric GEM AI algorithm). Using medical records to assess patient phenotypes and whole-genome or whole-exome sequencing, the Fabric GEM AI algorithm identified the causative gene as one of its top two candidates >90% of the time. A second example of the diagnostic potential of AI targets the finding that many rare diseases are associated with characteristic facial morphologies (such as Alagille syndrome, a multisystem genetic disease that presents with a range of clinical manifestations, and Angelman syndrome, a genetic syndrome that leads to severe physical and learning disabilities). In a report published in Nature Genetics (Hsieh et al. 2022), photographs of 17,560 patients with 1,115 rare disorders were used to develop a program called GestaltMatcher, which can successfully associate facial dysmorphism with the underlying genetic disorder. Both studies enable substantial automation of disease diagnosis and demonstrate the potential for AI to accelerate clinical diagnosis of patients with rare diseases.

Show your stripes

The future is looking bright, but there is still much to be done to ensure rare diseases are recognised as an international public health priority. Rare Disease Day provides us with an opportunity to raise awareness and highlight the challenges that are faced by the rare disease community, but it’s also a day to celebrate the progress that’s been made. So, join the thousands of people raising awareness of rare disease and ‘show your stripes’ on this year’s Rare Disease Day.

Amanda Henkel, VP, Strategy, Nucleus X Consulting (part of Nucleus Global)

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About Nucleus Global

Nucleus Global is the largest specialist medical communications company in the world, with 14 fully serviced agencies operating out of 14 office locations and 900+ medical communications specialists worldwide. Nucleus Global’s agencies deliver world-class compliant events, publications and digital programmes, supporting the marketing, medical affairs and publications teams of the biggest healthcare and medical brands in the world.

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25th February 2022

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