We’ve learned through experience and gained vital insights which translate into value for our clients. Here we share with you a few industry perspectives on critical issues in the commercialization of rare disease and gene therapy products.

By their very nature, rare diseases are often poorly defined.  This commonly leads to incorrect, non-specific (or even non-existent) billing codes, and just as detrimental to your market understanding, providers unintentionally using billing codes incorrectly.  Similarly, academic literature for rare diseases may be limited in quantity and is typically focused on those most severe patient presentations.  This ignores what we refer to as the “severity/incidence inverse”, or the tendency in a rare disease to find lower incidences of those with the most severe form of disease, while finding higher incidence of those with a less severe incidence disease.

The consequences of incorporating a commercial lens on market sizing far too late can lead to launch delays, inadequate resourcing, lack of investigator, expert and payor relationships and unrefined market strategies.  It is not uncommon to see organizations wait until Phase 3 to bring on a commercially focused team full time.  Furthermore, these roles are often headquarter-based with limited focus on insight gathering from disease specific experts and key opinion leaders.  This single-minded approach leads to an overreliance on billing and coding data and academic literature-based measures of market potential, which while important, are commonly less accurate in rare diseases and when taken out of clinical context can lead an inexperienced team to the wrong conclusions.


We at RCP have real-world experience with these challenges and can help you to identify common market sizing pitfalls EARLY in your commercialization planning avoiding costly misdirection of valuable effort, budget and time.

Clearly understanding and defining your market opportunity plays an integral role in everything from organizational expectation setting and thus company valuation, to field force sizing/structure and capital planning, yet this vital activity takes on unique challenges in the setting of rare diseases.

Fortunately, these common imprecisions of quantitative data can be minimized when combined with qualitative field-based insights.

Patient Identification (ID) is challenging in rare diseases and yet, it is the lifeblood of any rare disease organization.  We have repeatedly seen organizations begin the process of creating a Patient ID strategy just before, or immediately after, commercial launch and then have limited time to execute an effective strategy with little to no margin for error.

Often, your commercial organization’s ability to find patients is its most important function.  The most successful organizations operating within rare disease are masterful in their ability to identify patients. And it is therefore critical to start this process early and continue building on the initial framework along the commercialization timeline up to and continuing well past launch for the life of the therapy.

Your first Patient ID strategy iteration is unlikely to be optimized and implementing it at launch means significant time and money wasted when the inevitable need to refine becomes apparent. Further time and expense will have then be dedicated to relaunch a new strategy, train stakeholders, coordinate with vendors and partners and update any previously created materials.  More importantly it means that patients, living with often devastating conditions, will suffer longer without an appropriate diagnosis.


Patient ID involves creating provider urgency for screening, clearly defining those who need to be screened, removing barriers to appropriate screening, and simplifying access to testing.  This is often an iterative process.  Ideally, you will have wanted to implement a data-driven strategy based on real-world evidence, gain feedback from the field, evaluate areas for improvement, then optimize and initiate an improved version, all well before an anticipated launch.  By the time you are preparing for launch, the patient identification strategy should be operational with all stakeholders clearly named and proven processes in place. Patient identification should begin 18-24 months prior to launch at a minimum and can start with field-based insights from experts as early as possible.

Aside from the importance of a multifactorial patient identification strategy to drive a successful commercial launch, having a solid understanding of the diagnostic environment, patient profile, where patients are likely to be found and a sense for the incidence and prevalence can provide intrinsic value to support valuation.

In the commercialization of rare disease therapies, working to develop, implement, iterate, and optimize your patient identification strategy from the outset, vastly improves outcomes for both your organization and the patients you look to serve.

KOL or Key Opinion Leader Development, closely related to Key Investigator identification, is a pillar of any successful commercialization journey. However, this critical strategic factor is often not given the importance that it merits. Typically, KOL identification effort does not begin in earnest until mid or in even late phase III, however, KOL development cannot begin early enough. Therapeutic area experts represent a cornerstone of knowledge from which to build an accurate and effective market strategy. They can help to educate their peers, speak to investors and payors about the data and the merits of the product, but they can also be a formidable foe if you have not spent the time to build the relationship, share the science and respect their position as a leader in the field.

It is also regularly taken for granted that anyone can do KOL development – “it’s just talking to a bunch of doctors.” This is definitively not the case. We have seen good relationships turn bad when the interactions were not well managed; a problem that can be very difficult and sometimes impossible to fix. Another common misconception is that to be a KOL you must be aligned with a certain company – be their “friend.” This is unquestionably not the case. A KOL is a prominent leader in their respective therapeutic area. Their designation as a “KOL” is not indicative of their positive affiliation with a company.


KOL identification, the first step in KOL development, is comprised of data and databases, market research, and algorithms, but KOL development requires human interaction and the ability to build and maintain long-term relationships. A deep understanding for and excellence in KOL development only comes with experience and if done well can create lasting and invaluable relationships with thought leaders, including with those who were thought to be “unapproachable” or who “would never work with industry.”

KOLs are the physicians who understand the therapeutic area and who may be treating the patients that you want to find. They may be the ones who know how to diagnose or can give you collective feedback about how the diagnosis is conducted and where the challenges are. Their knowledge and feedback, willingness to review the data and provide insights, or speak on behalf of a company in support of a particular product because they believe in its transformative properties is immensely valuable and there is no viable substitute.

Some physicians will work with industry, some will not. There may be bad blood due to interactions with predecessors or product competition. Nonetheless, they are a KOL and it’s important any company or commercial team working to launch a rare disease product know who they are, what their position is and maintain a collaborative tone.

To be effective, interactions with KOLs must be on their level. You must be able to understand the data and articulate it’s benefits and limitations. You need to know how to effectively question and humbly debate and build trust and confidence in not only the team or company you represent, but what you are trying to accomplish by bringing a product to patients.

How do you find a patient with a rare disease? It’s like finding a needle in a haystack. What seems a rather straightforward question is deceptively complex. In rare disease, the first big hurdle to overcome is disease awareness. Do physicians even know enough about the disease to be able to make a correct diagnosis? Does the disease have disease mimics that can lead to a false diagnosis? Is there a diagnostic code? In the case of a rare genetic disease, can the anomaly be found on a gene panel? Is the gene on phenotypically relevant gene panels? The list of questions is long and beyond the scope of this case study but suffice to say that understanding the diagnostic landscape is an essential yet considerable undertaking that requires time and investment to do well.


The commercial team must be adept at developing and implementing successful patient diagnostic strategies globally. Success requires significant collaboration, cross-functional effort, and tactical pull through supported by research and analytics to enable a global testing resource customized to individual geographic areas as dictated by the commercial strategy.

How do you find a needle in a haystack? There are three approaches – you can recruit more people to help look, you can make the needle easier to see and you can decrease the size of the haystack. Which one is best? All of them.

It is not one of these components alone, but the cumulative effect of each part working towards the singular goal. Recruiting more people to look is essentially KOL Development [see Case Study 3]. Educated specialists are empowered to include a rare disease in their differential diagnosis if they are informed about how that patient will present in their practice.

Making the needle easier to see can be achieved on different routes. It is crucial to have an extraordinary understanding of diagnostic markers that lead to the correct diagnosis. While confirmatory tests like enzyme activity are necessary for the final diagnosis, it is rather unpractical to test every patient for enzyme activity if there is no clear suspicion of the disease. More useful are diagnostic markers that narrow down the patient population that require a confirmatory test. For specific symptoms that describe the disease, disease awareness is the correct tool, as the knowledge of each physician is the key to diagnosis. Specific laboratory markers however may be established in the diagnostic lab routine. So, instead of changing the behavior of the physicians, use it. That would mean identify tests that physicians routinely order for patients that have similar conditions and change those tests. For Example: implement genes into panels, add metabolites to mass spectrometry panels, or identify ratios of already measured parameters.

Making the haystack smaller is accomplished through enriched screening programs where physicians screen, past, current, and potential patients who fall into the enriched populations category for the rare disease you are trying to find. That requires a deep understanding of more common differential diagnosis that lack confirmatory testing or are more a symptom than a specific disease.

In addition to clinician-initiated testing and free or no-cost screening programs as well as prevalence studies, partnerships with laboratories and diagnostic experts are critical components of patient finding, which requires professionals who can talk to laboratory directors and diagnostic leaders in their own language.

Often in oncology and hematology we see a therapy entering multiple parallel studies in different tumor types.  Such approaches are scientifically wise for a compound that has demonstrated activity in pre-clinical and early studies – the race to see how many and which patients can be served by a novel therapy is an important contribution to patient treatment.  But which tumor type should be first and what are the factors that will contribute best to the long-term success of a single novel therapy?  Should a single brand or multi-brand strategy be employed?  When should these questions be asked and what are the inputs that help inform the optimal strategy?


Cross-functional, holistic assessment during the pre- and peri-launch periods is the best approach to ensuring maximum value creation for a multi-indication asset.  Early insight gathering can also de-risk a program by allowing for fine-tuning of individual trials and endpoints as well as determining where to invest in trial acceleration.

Without early commercial planning during development, timing and resultant outcomes for the asset program can be driven by clinical development timelines.  This can result in suboptimal achievement on returns/multipliers for what could be a portfolio in a product.  In instances with parallel trials, the first commercial activities may be driven fully by the fastest trial to read out which can impair price.

Careful consideration and scenario modeling must include a synthesis of all target indications:

  • Current and future competitor prices and clinical values;
  • Patient journeys;
  • Unmet needs;
  • Patient population and sub-population sizes;
  • Treatment durations;
  • Dosages; and importantly,
  • Individual study designs, endpoints, and velocity of the asset’s clinical studies.

While this example references oncology and hematology, the same principle of involving commercial planning early during development to drive optimal performance of a product holds true independent of the therapeutic area.

How many people think of the skeleton when they see a person? That is probably the last thing on their mind. But would the face, muscles, or voice be where they are and have the same collective impact without the skeleton that supports them? Operations is just that – the skeleton, the backbone of any commercial organization. Operations is a broad term that covers a multitude of areas, such as strategy & planning, business intelligence, HCP engagements, marketing, and congresses, as well as marketing and field operations – all of which must be delineated ahead of even building a marketing or field team.

However, operations as a function tends to be the last piece to considered in the development of a global commercial organization. This can lead to a lack of structure, well-rounded processes, and strategies. Most importantly, and with some trepidation, companies often learn along the way about how to be compliant, instead of being prepared in advance and preventing a host of issues.

There is also a difference between operations and operational excellence – not all operations functions are created equal. Building and running a best-in-class operations team requires a thorough understanding of all the functions and teams that fall under it, how these teams will interact with each other and the experience to know how and when to initiate and grow each team. 


RCP can leverage its launch excellency as well as commercial daily business expertise to help create an operational function, which will work cross-functionally (and globally, when that point in the organization is reached) across your organization and assure that business processes and strategies are built, implemented, enforced, and optimized regularly.

A growing commercial organization would save time, money, and resources if operations were to be built in the initial phases of a clinical study. This will ensure the organization has critical processes in place, such as the MLR/PRC process which reviews and evaluates externally and internally facing branded and unbranded materials well ahead of any launch. Moreover, it ensures business strategies are built, ahead of any field representatives being onboarded or marketing teams being created. This also rules out the danger of working in silos once these teams are created, as operations is the backbone that helps to keep these independent pieces working together. Being compliant is crucial to the entire organization and operational excellence ensures that compliance is integrated into business processes and strategies at the forefront.

A commercial organization with a well-established operations function will run in a smooth, lean, and efficient way, and provide critical support as the company grows and looks ahead to future expansion and product launches. Such a robust operations function sets up the organization for success. Processes that are implemented and learned early enable the team to grow while having already adapted to company policies rather than having to learn new processes and break bad habits.

Furthermore, it is imperative that the operations function is supported by efficient and scalable IT solutions. Operational strategy must be continuously refined, and focus should be given to optimizing the operational excellence team, structure, and day to day activities.

Before launching a therapy in the rare disease field, a lot is unknown. And while the common nature in humans is to preferably have knowledge before acting, a market launch for a rare disease therapy usually doesn’t allow for this comfortable situation. You often must act before you definitively know all the answers. One of the advantages of launching a rare disease product usually is the absence of competition, or the possibility to be the first in the market. However, the downside is, that there is no established market and therefore a lot of uncertainty.

So, while having answers makes planning much easier, one of the crucial points in rare diseases is to know the questions and when those questions need be answered. It starts with one of the most crucial questions in any strategy planning. How big is the market actually?

The market size in rare disease is basically the number of patients that can be treated. The general assumption in any rare disease is that most of the patients are yet undiagnosed, because the lag of general knowledge of specific rare diseases by general physicians. That is on the other hand a result of a missing treatment. Finding rare disease patients usually involves quite a lot of investment additional to the investment in developing the treatment. Investing always comes along with a certain risk, but risks want to be managed. So, knowing all the potential patients before developing a treatment would be fantastic, but it also involves a lot of upfront investment that could be gone if the clinical trials fail.  So how can you find patients without breaking the bank? Can you improve the regular diagnostics of that disease early enough and what to you need to spend? How good do I need the data to be at a certain point during my launch? Some rare disease companies try to get the most precise data early on, because better data usually leads to better decisions, but is that really the case?


Having questions when trying to launch a rare disease therapy is a good thing. You don’t need to have all the answers, but you need to prioritize them and know when you need the answers. Prioritizing questions will help to build the strategy. Since rare diseases are unique there is no “one size fits all” approach. However, the fundamentals are comparable. One approach can be working from top down, starting with what you want to know (for example market size). Then thinking through what you need to know to answer the question.

Using market size as the example, the series of questions might include: How many patients have this rare disease? Is the treatment I’m developing suitable for all of them? If it is not, then why? If the burden of treatment is larger than the disease in mildly affected patients it would not make sense from an investment perspective to search for mildly affected patients? When you know which patients you are looking for, you then need to ask, “How do I find them?” Can I use the same approach to identify all of them? How many patients already have a diagnosis and how many patients are estimated to be undiagnosed? For patients that already have their diagnosis, how do I find them? For patients who don’t yet have a diagnosis, what needs to change to enable a diagnosis?

The more you question and the more you challenge the “why?”, the more specific and unique your questions become. The better your questions, the better the answers will be in the end and ultimately the more refined your strategy will be. This is an area where RCP is well positioned to help provide guidance on the right questions to be asking at the earliest stages of commercialization and/or launch and confidence in securing the right answers. So go ahead. Start asking.