Historically, orphan drug development has existed on the margins of R&D spend, but increasingly, this product class is attracting
attention and value. With the blockbuster model wearing thin, the pressure for lower cost drugs with better outcomes is growing.
It's time for the industry therefore to diversify its strategic approach.
The benefits of shifting focus to orphan drugs are many, including a streamlined approval process, patent extension and exclusivity,
tax credits, and smaller clinical trials based on narrow indications. But as competition moves into these niche spaces, everyone
will be looking for an opportunity to get an orphan-drug designation (ODD). This strategy may lead to additional scrutiny
and intensify the need to demonstrate the economic and clinical value of a product as it applies to a particular population
The pursuit of orphan drugs has implications for change across the entire business. It will require a new R&D approach that
addresses economic and clinical value data, and goes beyond randomized clinical trials for regulatory approval to alternative
types of data (e.g., observational or "real-world" studies that demonstrate product value over time in real-life scenarios).
Companion diagnostics used to identify the patient population most likely to benefit from orphan drugs represent another key
area that biotech and pharmaceutical developers will need to explore. This area may present licensing and acquisition opportunities
on both sides.
The growing emphasis on orphan drugs and more targeted diagnostics represent an increasingly personalized approach to medicine
in general. An inevitable impact will be shrinking target patient populations, where the majority of blockbuster drugs will
be suitable for a significantly smaller group of patients, the number of whom may well fall within the definition of rare
diseases (6–8% of world population) (1). As genomics define specific subpopulations within larger disease conditions (e.g.,
hypertension), bio/pharmaceutical manufacturers of all sizes will increasingly need to shift to thinking about drug development
within the context of the orphan model.
In this context, companies will have to seek indications for their products within narrower patient populations and build
a large population of patients incrementally, rather than as one single, huge population used in the rolling blockbuster model.
To develop a successful model based on orphan drugs, manufacturers will need to adopt a new approach to both product development
Rising product development costs, stingier public and private reimbursement, and increasing regulatory hurdles mean that companies
are struggling more than ever to bring new products to market at prices that sustain ongoing investments in innovation. Ongoing
waves of blockbuster-drug patent expirations are offering insurers cheap and effective generic drugs. Concurrently, rare but
significant side effects (as in the case of Vioxx) have eroded regulators' willingness to approve drugs for primary care indications
without prohibitively large and expensive clinical trials (2). Additionally, the situation is complicated by a shift in the
balance of power among industry stakeholders, each of which may require different evidence to be convinced of a product's
Instead of thinking big, innovators need to think small. If a company shrinks the denominator to just the segment of the market
that genuinely benefits, then the value element starts to look a lot better. This shift can mitigate business risk, as well.
Rather than seeking a single indication for one, large group of patients, the rolling blockbuster approach for orphan drugs
segments the market for a drug more minutely, creating a large number of target populations in which the drug's value can
be assessed. Such an approach reduces the risk inherent in clinical trials because the binary outcome (reimbursed/not-reimbursed)
applies only to the small segment under consideration. The population becomes the sum of those small segments, eventually
comprising a much bigger population.
Compared with the bleak landscape of aging blockbusters, the orphan-drug market is appealing, especially when considering
drugs that successfully made the leap from orphan to rolling blockbuster. Take, for example, Botox—a drug approved with orphan
status in 1984 to treat uncontrolled blinking, neck pain, and muscle spasms. Since then, FDA has approved numerous additional
indications, including the treatment of frown lines (2002) and migraines (2008). Today, there are 5 million doses of Botox
administered annually in North America, which translates into approximately $1.5 billion in sales.