In pharmaphorum’s rare disease focus month, Karl Simpson of Liftstream explores whether a different set of skills, experience and talent are required to develop orphan drugs, and questions how different the business model of rare diseases is. The article was originally published in pharmaphorum on 18th February 2014.
The biotechnology sector has long been seen as the innovation engine capable of driving a renaissance in a beleaguered pharmaceutical sector and over the past 12 months, this engine has been roaring. One of the growth propellers driving this engine has been the rare diseases business. Successful new product launches, numerous licensing agreements, acquisitions and many initial public offerings have heightened both sector and investor interest in this orphan drugs segment
“But how different is the business model of rare diseases, and does big pharma ‘get it’?”
This question is asked not only of the R&D approach but equally of the commercialisation. Culturally there are significant impediments for many large pharmaceutical companies in orphan drug development. The internal competition for R&D budget allocation and the pricing model for rare disease therapies are just two of many specific issues. For large pharma to build rare disease franchises effectively, they need executive and cross-function leadership with conviction to the business model.
This begs a deeper question: which is whether the experience, skills and talents employed to develop orphan drugs are starkly different from the mainstream pharmaceutical business? Those who’ve long worked in rare diseases cite the uniqueness of the business and imply that those from mainstream pharma could not adapt to the particular orphan approach. But given many already have this background, are the differences really so contrasting from so-called traditional drug development?
The pharmaceutical industry has a very long history of creating vertically integrated companies. The recent output of this has been poor levels of R&D productivity and innovation. This declining output has necessitated a relatively recent and growing wave of externalisation and collaborative working, giving way to a more open and partner-oriented culture which is still very nascent. It is this collaborative culture which is absolutely central in defining the difference in rare diseases. Success in the rare diseases business demands the very highest levels of multi-stakeholder partnerships.
At the very heart of this constellation of stakeholders is the patient. The proximity to patients, and the engagement with them or their advocacy groups, inculcates a ‘patient-centric’ mentality which is a key success factor in those employed in the rare disease sector. The very small populations of patients mean companies and their employees become very close to the individual people they’re trying to treat.
“For large pharma to build rare disease franchises effectively, they need executive and cross-function leadership with conviction to the business model.”
The patient community of any rare disease you choose to nominate is often strongly represented by a group of highly active, strongly passionate and well-organised people comprised of patients, parents and volunteers who are campaigning tirelessly for recognition, funding and research into their particular disorder. These advocates have been hugely impactful in the field of rare diseases and remarkable outcomes have resulted from their incalculable commitment. People who choose to work in rare diseases have to be prepared, as well as show an ability, to work constructively with these individuals or groups, even when their objectives are not necessarily aligned. The patient stakeholder not only exemplifies passion and dedication but often possesses extensive knowledge of their disease and so effective interactions with them are integral to the development of better disease knowledge leading to possible therapeutic breakthroughs. This engagement demands leaders to possess advanced communication skills, as well as empathy and relationship building skills.
One such example is the ultra-rare disease of Alkaptonuria (AKU). Nick Sireau, the father of two children with this rare genetic disease, founded the Alkaptonuria Society and undertook huge efforts to identify people across the globe with Alkaptonuria, engage with academia and physicians and to increase understanding of the disease. His efforts have led to a possible breakthrough collaboration with Swedish Orphan Biovitrum (SOBI) who have been performing trials of their tyrosinaemia treatment (Orfadin) for treating AKU, while patients are also being provided with the therapy on a named-patient basis.
Commercialisation of a rare disease therapeutic is often very different from the more common diseases. Owing to the smaller patient populations, the opportunity exists for smaller biotechs, often the originators of such innovative therapies, to commercialise their own products. However, small patient populations in rare diseases do not necessarily equate to rapid or effective launches. The identification of patients with these rare diseases can often require very specific strategies to recruit patients and engage with physicians. Forecasting the resource and infrastructure required can be incredibly difficult with such small and unpredictable patient numbers. With disease diagnosis, a primary issue in rare diseases, the identification of patients is notoriously difficult and has commercial implications. The provision of therapies can also require high levels of physician education and training.
“The very small populations of patients means companies and their employees become very close to the individual people they’re trying to treat.”
Named patient usage programmes
Given rare disease therapies are often the first in class and treat unmet medical needs, there is a clear desire on behalf of the patients for early access to new treatments. Therefore, Named Patient Usage Programmes (NPUs) are a key feature of the rare diseases business. NPUs demand the integrated knowledge of many of the functions inside the company. The consideration to offer a drug via an NPU requires medical affairs teams to ensure physician training and adequate educational materials are provided. The regulatory affairs and clinical teams must advise on the inclusion criteria for eligible patients and prevent any contravention of the regulations or actions which could later jeopardise ongoing clinical trials. The manufacturing and supply of drugs must be sustainable. Oversight and management of these functions are imperative for those wishing to lead effectively in a rare disease therapeutics company.
Adaptable in uncertainty
Innovation is the process of addressing the unknown. This is acutely true in rare diseases. In whichever direction you look there are huge unknowns that create ambiguity. A lack of disease history and the absence of existing treatments impose challenges at each stage of the pathway towards new therapies. In discovery and development, there are a plethora of hurdles; a lack of recognised and validated animal models, biomarkers as surrogate endpoints are rarely available or acceptable, little or no reference data, and comparators are often ill-defined. In clearing regulatory approval, the risk/benefit balance between promising clinical trials and the real-world clinical data needs to be accepted. Effective dialogue with regulators must be achieved and opportunities for approaches such as conditional approval explored. In achieving pricing and reimbursement, the landscape is fast changing, with dialogue increasingly oriented towards the use of real-world clinical evidence as a determinant of value as the cost of orphan drugs comes under increasing scrutiny by payers.
However innovative the science, clearly the translation of this science into accessible medicines is the subject of considerable unknowns. Leaders, therefore, must exhibit the qualities to manage effectively in highly ambiguous situations, while continually managing innovation and retaining strategic agility.
While there are more similarities than differences between mainstream pharma and rare diseases, a rare disease business must have leadership that possess the ability to adapt to the nuances and successfully preside over the multitude of function-level specificities.