Orphan drug medicines and therapies targeting small patient populations have, in recent years, generated excitement across government, research communities, and the biopharma industry. By 2020, the rare and orphan drug market is forecast to account for 20.2% of worldwide prescription drug sales (excluding generics) and total $178 billion in annual revenue.[1] To put this into context even as recently as 2010 sales of Orphan drugs accounted for less than 10% of worldwide prescription sales[2].

As well as the Orphan disease drugs, although sometimes overlapping, there continues to be excitement and industry commitment in developing programmes targeted at more defined patient populations; this is expected to continue to flourish over the coming years. Leading the way in targeted therapies is the immuno-oncology (IO) field. Currently there are over 1000 IO agents in clinical development, filed, or marketed, in the five core mechanism of action (MOA) groups: bispecific antibody, cancer vaccine, cell therapy, checkpoint modulator, or oncolytic virus[3]. Trials within IO are becoming ever more targeted but at the same time increasingly common place. As of December 2018, Keytruda alone was involved in over 550 ongoing combination and monotherapy clinical trials[4]. Considering in 2010 there were only 5 documented new clinical trials involving IO agents the industry’s enthusiasm around this type of therapy is clear to see.[5]

During BIO-International in Boston 2018 Cello Health surveyed members of the biotech and life science community to ascertain some of the biggest factors influencing the market. The advent of evermore personalised medicine, focused on smaller patient populations was seen as a core feature. We reported these trends here

Given Biotech companies are often working at the forefront of scientific breakthrough we decided to use BIO-Europe Fall in Copenhagen and JPM San Francisco January 2019 to survey further stakeholders to identify the priority challenges facing Biotech companies in relation to the continued focus on small patient populations and targeted therapies.

Over the next few weeks we will describe 5 challenges on this topic that appear to be at the forefront of Biotech executives’ thinking. These topics are:

1. Finding patients

2. Challenges with clinical trial design and recruitment

3. Regulatory requirements

4. Long term revenue stream

5. Reimagining commercialisation.

This week we explore the challenges of ‘finding’ patients and the overall low levels of awareness with rare and orphan diseases and advanced, novel therapies.

It is estimated that there are over 350 million people living with a rare disease. This may appear to be a large number but when it is considered that there are over 7,000 documented rare diseases, of which 80% are genetic, it is clear that in many cases the incidence level is very low.[6] To briefly illustrate this, take for example a rare disease called Hutchinson-Gilford Progeriathis disease affects about one in every 8 million children and, due to a genetic mutation, causes the appearance of rapid aging beginning in early childhood. Symptoms often include baldness, a large head relative to their body size, limited range of motion, and most tragically, a hardening of the arteries in many cases which increases the chance of heart attack or stroke. In medical history, only about 100 cases of Progeria have been documented with few patients living into their 20s.[7]

Due to the lack of knowledge around many of these diseases it can take many years for rare disease patients to receive an accurate diagnosis. It is estimated that the length of time from symptom onset to an accurate diagnosis involves on average 7.3 physicians and takes around 4.8 years[8]. Owing to the rarity of many diseases it is often the case that Biotech companies lack the appropriate skills, capabilities or revenue to: identify patients, identify thought leaders, develop treatment algorithms, support improved diagnosis, develop referral centres, connect specialists and build awareness. From our discussions with multiple Biotechs we found it common place that there were difficulties in locating patients; often there were difficulties in dealing with Patient Advisory Groups (PAGs) with a feeling that PAGs are often not optimally organised lacking experience, resources, infrastructure and commercial expertise. Additionally, there was a feeling that they often don’t understand (or are suspicious of) how best to engage Biotechs in particular.

This being said we are living in a world of ever increasing technology, especially in regards to rare disease patients who are often much more informed and demanding ‘partners’ in their own healthcare; they understand they have options and use information, social media and data about themselves and providers to get the best treatment available. In this respect rare disease sufferers and their caregivers are often different from other groups in that they are extremely motivated information seekers. The internet and PAGs have played a hugely important role in developing communities and networks for people living with rare diseases and their families to connect with one another and discuss available research. Finding information, locating speciality doctors, and meeting fellow patients has never been easier. Often these charities are instrumental in helping identify new treatments and shaking up the status quo. An example is Findacure a fabulous charity we support here at Cello Health. However, even in the current climate where patients actively seek information they are often not aware of a small Biotech developing a new therapy that could directly help them; and the Biotechs are often either not aware of them or not actively engaged.

In regards to IO and targeted oncology therapies finding patients is less of an issue; although awareness around novel therapies still has some was to go. Health communication has made impressive progress in the last 15 years and research on communication interventions have received significant support from health institutes around the world. Nowadays, patients have a multitude of sources available from which to get information about health topics. Nevertheless, cancer patients’ needs and interests present much variability, with only a minority of patients interested to learn as much as possible about their disease, and most of them depending on their physician for information.[9] This can lead to difficulties in accessing patients. Often first line community HCPs are not aware of the latest treatments and advances in IO therapies. Even when patients are referred to a specialist physician, specialists are often either concerned/unable to prescribe new therapies; as they feel they have to justify their decisions to payers or are concerned over the lack of long term clinical data. So although finding patients may not be as difficult in regards to IO therapies many aspects of accessing them can be; we will explore these challenges in more detail in subsequent parts of this series.


Rare and orphan diseases often have a charity, PAG or informal patient networks already in place. Many Biotechs we have spoken to appear so focused on their exciting science, platform or Mode of Action (MoA) that they lose sight of the patient at the centre. It is critical that Biotech companies look to engage with patients and PAGS from an early stage of development (ideally from first in man trials). Not only will this allow them to understand in more detail the needs and unmet needs of the patients – it will allow the patients to get to know the company and be advocates for the further development of the therapy. Their early involvement will also help inform the extent of the challenge and infrastructure that needs to be addressed in order to meet the unmet need and realise the value of the asset which may go beyond a biopharmaceutical solution.  As part of this early exploration, it is vital to map the patient journey, and to explore in some detail the various pain points and pinch points in the pathway to help design targeted, patient-orientated solutions fit for a rare or orphan disease population. When developing a solution for a rarer, smaller population of patients Biotechs need to consider questions such as: Where are the patients today? How findable are they? Is this a hereditary disease with possible ‘hot spots’?  Do patients get diagnosed today and how simple is that diagnosis? Where are they treated? How are they treated? Who treats them? 

Understanding the magnitude of the challenge from the patient perspective will help define the right strategy and the right solution for the company and the asset.

Next week we will explore the Challenges with clinical trial recruitment and design...

[1] https://medium.com/@saatchiwellness/how-is-rare-disease-marketing-different-from-traditional-medical-marketing-996052107378

[2] https://www.washingtonpost.com/business/economy/high-prices-make-once-neglected-orphan-drugs-a-booming-business/2016/08/04/; EvaluatePharma

[3] Global data immunooncology development trends and opportunities Nov 2018

[4] Global data immunooncology development trends and opportunities Nov 2018

[5] Annals of Oncology 29: 84–91, 2018; Ther Adv Med Oncol, Vol. 10: 1-12, 2018

[6] https://www.shire.com/-/media/shire/shireglobal/shirecom/pdffiles/patient/shire-diagnosis-initiative-pag-leaflet.pdf

[7] https://www.fool.com/investing/general/2013/08/04/5-of-the-worlds-most-ultra-rare-diseases.aspx

[8] https://www.shire.com/-/media/shire/shireglobal/shirecom/pdffiles/patient/shire-diagnosis-initiative-pag-leaflet.pdf

[9] Searching for cures: Inner-city and rural patients' awareness and perceptions of cancer clinical trials (m.geana et al. 2016)