Over the last few weeks, we have reviewed some key challenges that, based on our interviews at various biotech congresses, appear to be at the forefront of Biotech executives’ thinking.

The first 3 articles focused on bringing rare and orphan diseases and targeted, advanced, novel therapies to market. We have explored the challenges of finding patients, the challenges with clinical trial design and recruitment, and regulatory requirements. Last week we shifted our focus toward the commercial challenges Biotechs face when bringing therapies to market, highlighting some of the long term revenue stream challenges arising in rare and orphan diseases. In this final article of the series, we focus on some of the challenges associated with commercialisation, exploring ideas around re-imagining what it takes for a Biotech with a novel therapy to successfully commercialise a product.

The idea of ‘going alone’ can be tempting; especially with a drug targeted at small, identifiable patient populations. Commercialisation feels ‘doable’ given the potentially lower clinical trial costs and smaller commercial organisation required for success. There are certainly many cases where Biotechs have built their commercial footprint and successfully launched products. For example Alexion with Soliris, a medication used to treat paroxysmal nocturnal hemoglobinuria (PNH); and Santhera with Raxone in LHON or more recently Alnylam with Onpattro; the first-of-its-kind targeted RNA-based therapy to treat polyneuropathy of hereditary transthyretin-mediated amyloidosis (hATTR amyloidosis).

However, too often we see Biotechs overly focused on the science and getting the product approved, without early consideration of the market, competitive and commercial implications. They frequently enter Phase 3 without considering the commercial implications e.g. indication prioritisation, market sequence, pricing and reimbursement strategy and organisational build plan, let alone the basics around their market development and/or launch plan.

It is well known in the Biotech world that pricing and reimbursement is potentially the biggest challenge to overcome. Orphan products in particular often demand an extremely high price. Take for example Takeda/Shire’s Orphan product Obizur for Acquired Haemophilia A, a rare form of haemophilia that typically affects 1.5 people per million. Although price varies per patient a course of treatment can often cost $200,000 - $500,000. Pricing is even more of a challenge when focusing on Orphan diseases, as often we do not have natural history data on these diseases, meaning we do not know how the disease is likely to progress. This makes it very difficult for companies to justify a high price and prove their product is making significant long term improvements to a patient’s life. However, as we have seen Orphan products often have a list price that is in the hundreds of thousands of dollars a year. This is further complicated for many advanced and gene therapies that offer the potential for ‘cure’. At the time of writing the health technology organisations in the US, the UK and Canada are collaborating to develop a methodology to ‘value a cure’.

Many Biotechs looking to commercialise their own products are well aware of pricing and reimbursement challenges. From our experience, it is often the critical commercial questions they are not addressing that leads to sub-optimal commercialisation. Those that do address these elements, often leave things too late and due to limited time, resources and finances, find it difficult to prepare for a successful launch.  

From our experience, the following six areas are often de-prioritised, overlooked, or tackled too late by many Biotechs. This is not exhaustive, but highlight some areas worth focusing on to optimise the chances of successful commercialisation:

Company vision and strategy :

Most Biotechs start life with a handful of passionate senior executives, and, as science is the focus at this early stage, clinical development scientists. As the company grows and the pipeline matures other functions come on board including a Chief Commercial Officer and the beginnings of a commercial organisation. This is a busy and critical time for any biotech who has made the decision to ‘go alone’. Not only are there a significant number of decisions to make, and a product to launch, but new staff members are added weekly who have none of the history or background, but clearly skills and experiences that the company seeks to add. Many emerging Biotechs, however, fail to take the time to reconsider their overarching vision and strategy at a company level. This is an extremely important part of engaging and aligning the growing team and can help enormously as an asset is ‘passed-over’ from development to commercial and as an emerging cross-functional team establishes itself. 

Regional capabilities:

One of the biggest decisions for Biotechs hoping to commercialise their own assets is deciding in which countries and regions they have the knowledge and capabilities (and desire) to commercialise themselves and where it would be beneficial to partner with a local entity. In reality, it is unlikely that any Biotech commercializes a product, especially a rare disease product, on a global scale on their own. It is important to consider a number of aspects when deciding where to go alone. In which markets do you have capabilities, or could readily build capabilities to launch? What will it take to be reimbursed and launch successfully in that country? Have you undertaken detailed patient journey mapping in these markets? What level of infrastructure, treatment algorithm, treatment centres exist? Which markets do you have relationships with KOLs? 

Many rare diseases have epidemiology hotspots. Are there countries that have a particularly high or low prevalence of the disease or concentration of patients? When all these aspects have been considered it is then important to consider launch sequencing. Where is best to launch first? Which countries to launch subsequently? Where will partnering be optimal? Are there territories in which launch isn't worth considering? This is a critical part of the commercialisation process that is often left too late, especially if you overlay the next section on follow-on indications and the opportunity for the future.

Cross-indication Thinking:

Biotechs working with targeted, advanced, novel therapies must consider the pipeline of indications coming for a particular asset.  We often see Biotechs so focused on their lead indication that they fail to consider the implications of these big decisions on their follow-on indications which may have greater strategic or financial potential. Blinkered decision making at this stage can cause considerable harm to the potential of follow-on indications; their access, reimbursement and overall launch success. Many Biotechs invest in prioritising their assets and indication sequence through development, but then forget to consider the wider indication strategy when commercialising. It is critical that the company considers future indications and markets when making crucial commercial decisions about the lead indication from dosing, device and pricing through to the scientific platform, the value proposition, positioning and messaging. If they don't, they risk impeding the success of their portfolio in a product. 

The scale of market development required:

A topic we focused on in part 1 and 2 of our series; awareness around rare and orphan diseases is often low, the healthcare infrastructure around the patient is often under-developed and their journey poorly defined.  Treatment centres may not exist, physicians may be poorly trained without clear pathways or treatment algorithms in place. Gaining a deep understanding of how underdeveloped a market is and what it will take to develop it is crucial for any company looking to commercialize a rare or orphan treatment given the significant investment it could take to raise awareness, to build infrastructure and ensure the market is ready for their new treatment

Detailed competitor understanding:

Although companies developing products for rare diseases may well have fewer competitors than traditional products it is important to consider present and future competitors in detail. Although many Biotechs may have an understanding of which companies are currently in their space few have undertaken detailed scenario planning. Doing this is likely to optimise long term commercialisation.

For a small team, many of these areas may require external support. Let’s not forget that Biotechs nearing commercialisation are rapidly expanding, developing capabilities and building operations. We often hear people describe “building the plane whilst it is taking off.”

Sometimes, however, it makes sense to slow down and take stock. Yes, there is a lot to get done, but starting earlier and taking time to define a clear cross-functional strategy, is critical to paving the way for a successful launch and overall faster growth, having made the right choices. It is vital for any Biotech to consider to what extent they need to build internal capability vs. partner as well as understanding whether it is critical they complete the work internally or invest in third party support.

In conclusion

As we have discussed through this series of articles, Biotech companies face multiple challenges when bringing targeted, advanced, novel therapies focused on rare and orphan diseases to market. At various points actions can be taken to improve the possibility of future commercialisation success.

Firstly, 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 does this allow them to understand the needs and unmet needs of the patients – it will allow sufferers to get to know the company and be advocates for the further development of the therapy. Their early involvement will also help inform and develop the infrastructure required to address the needs and build solutions that wrap around any biopharmaceutical product.

Secondly, engaging with other expert organisations in the space to help navigate the clinical trial recruitment and design challenge in particular when designing one of the first clinical trials conducted in a specific patient population is paramount. Biotechs will be wise to work with organisations such as NORD and those specialised in rare disease clinical trials design such as  IDEAL and ASterix. They will also work with companies utilising technology to improve the likelihood of success. Social media can be critically important in building relationships where patients and caregivers communicate and engage. Even in the early stages of development platforms such as Pulsar can ensure meaningful endpoints are built into the trial design.

It is also important to consider the current and future regulatory requirements from an early stage of development. This is paramount in orphan drugs and novel therapy development where regulations are often changing. There are multiple agencies across the world that focus on providing drug regulatory and quality assurance services. They are able to provide guidance from an early stage of development in regards to national and international scientific and regulatory advice, Orphan drug applications and a number of critical regulatory hurdles that are likely to enhance the likelihood of future commercial triumph.

There is finally a need to carefully consider the company, product and pipeline strategy from early stages of development, whilst considering a well-defined launch strategy. It is important to review it with a specific perspective on potential future indications and trends in target markets. It may well be advisable to use consulting partners, like Cello Health to undertake deep scenario-based work to provide a deeper understanding of the future challenges the business will face. It is important to recognise your own capabilities, embrace partnership where it makes sense in the early stages of commercialisation.