More than 40 years ago in 1983, the Orphan Drug Act was passed in the US to support and incentivise the development of rare disease therapies. Despite the over 6,000 orphan drug designations (ODD) granted by the FDA since then, it is estimated that only around five percent of rare diseases have an FDA-approved drug and up to 15 percent of rare diseases have at least one drug that has been developed for the treatment, diagnosis or prevention of the condition. The gap between unmet need, designation, and approval creates a clear opening for a growing number of rare-disease-dedicated pharma companies looking to pick up the last mile where others have left off.
A New Breed of Buyer
Companies like Zevra Therapeutics are emblematic of a new breed of specialty players that have come into being which purely focus on strategically acquiring assets in the rare disease therapeutic space. “The company had brought together several assets and businesses at different stages of development. The opportunity was to pull those pieces together, focus on doing a few things really well, and drive real value for patients,” details the company’s President and CEO, Neil McFarlane. “That became the strategy. We acquired companies and assets, aligned around the highest-value priorities, and focused execution where it mattered most. By doing that, we were able to start unlocking value,” he adds.
Similarly, Mirum Pharmaceuticals focuses on rescuing overlooked drug programs to treat rare diseases, especially those affecting the liver. “We are very focused on medicines that tend to be overlooked by Big Pharma because they do not meet the threshold of being expected multi-billion-dollar products. These are often high-impact medicines where there is a misunderstanding of the patient population, the demand, or the real-world disease burden,” explains Chris Peetz, the company’s co-founder and CEO.
Theseplayers argue they are better equipped to advance certain rare disease therapies than the entities that discovered them. “One pattern we identified early in our rare disease pursuit involved innovators holding one approved product alongside a development pipeline, essentially trying to operate as two distinct types of companies. Typically, growing organisations excel at one or the other. Because our expertise lay heavily in commercialisation, we would approach these companies to acquire their approved products. In our view, we could provide a more dedicated effort, particularly when integrating the product into a focused commercial rare disease portfolio,” says Matt Heck, CEO of Sentynl Therapeutics.
On the Hunt for the Overlooked
For Peetz, the story began with the express purpose of finding the right diamond-in-the-rough opportunity and eventually led to the formation of a flourishing multi-product company. “One of Mirum’s founding investors was Frazier Life Sciences, which has a company creation model where they work closely with entrepreneurs to start new companies,” he explains. “They invited me to lead a search focused on overlooked rare or liver disease programs. I spent a little over a year looking through large pharma pipelines to understand what had been deprioritised or underappreciated. That process ultimately led to the creation of Mirum.”
In December 2025, Mirum announced the acquisition of private liver disease biotech Bluejay Therapeutics for USD 620 million, showcasing what Peetz describes as the company’s ability to take externally sourced assets and unlock their full potential. “External sourcing is really part of who we are. It’s how the company started, and it plays to our strengths.”
Sentynl applies a similar externally sourced model, beginning with a systematic screen of the regulatory landscape. “To begin, we navigate the FDA regulatory orphan drug database to review all orphan drug designations, which demarcate rare disease product candidates. That is the most concise way to describe our initial search mechanism.” From there, the priority is fit, explains Heck. “The secondary phase involves assessing strategic fit. Over 50 percent of those designations are likely within oncology, which is not our primary area of focus. We filter the remainder to locate our thematic focus, which currently spans pediatric neurology to metabolic disorders. That said, we remain open to expanding into other disease states in the future.”
Like any business development decision, ensuring a right fit for an opportunity within the organisation was key in Mirum’s case as well. “The Bluejay acquisition and the asset brelovitug are a good example of how we approach these opportunities. Before the acquisition, we had followed Bluejay for a couple of years. The data was always very compelling and seeing a 100 percent response rate in any setting gets your attention…Still, one of the big questions was simply: how many patients are there? That is where we felt we had a different point of view. As a team that understands patient finding, referral patterns, and treatment dynamics in rare liver disease, we believed the opportunity could be more substantial than previously understood. This creates a mutually beneficial opportunity for both Mirum and Bluejay, and most importantly, for the patient community.”
Small by Design
Beyond just determining a strategic opportunity fits within the organisation’s capabilities, navigating the healthcare landscape and a fragmented stakeholder network is a factor of success in rare disease that these players recognise as key. “There is often a deficiency in support and understanding for these rare conditions,” says Mirum’s Peetz. “Since acquiring these therapies, we have focused on improving awareness and diagnosis of these rare diseases, so patients who may be affected can be accurately identified and appropriately treated. This is a common thread across rare diseases. By supporting disease awareness, genetic testing, and diagnostic pathways, we have seen more patients diagnosed and treated with these therapies,” he adds.
McFarlane of Zevra affirms that focusing squarely on rare disease requires a close collaboration with the specialists and centres who are uniquely suited to tackle the awareness and diagnostic issues. “For us, it means concentrating our efforts on roughly 40 centres of excellence across the US…Our goal has been to ask a very simple question: how can we best support these centres of excellence and provide a fully integrated platform that truly meets their needs?”
From a commercial standpoint, building a dedicated network which they can continuously leverage across products is what allows these asset-gathering companies to be efficient and succeed where larger pharma may not. As McFarlane puts it, “There is a high degree of overlap among the stakeholders involved. That allows us to take a high-touch, high-support, non-traditional approach that is really required in rare disease, where patient populations are small and every case is complex. We have been very deliberate about not expanding into larger or less focused rare disease markets. With a relatively small team of about half a dozen people each in sales, patient services and medical affairs, we are able to deliver what these centres and patients need.”
Heck of Sentynl agrees that expertise, not simply scale, is the key to creating impact for patients. “The disease states and distribution channels are immensely complex, and we simply could not succeed without the dedicated experts on our staff,” he points out. “We currently have 20 personnel, and together we provide access to critical medications in more than 40 countries globally.”
And of course, collaborative effort internally and direct partnership with organisations close to patients is the ultimate mark of a strong approach. “This success relies entirely on our collective team, our consultants, and our external partners across distribution, access, and advocacy,” asserts Heck. “I must also highlight that patient foundations are absolutely critical. There are no greater experts in the field.”
Purpose as Strategy
Bringing rare disease therapies to patients can be extremely challenging, meaning that a strong sense of mission is vital to getting them over the line.
“It’s really important to me that the team has the same level of care and excitement about what they are working on,” says Mirum’s Peetz. “Talking about patient stories, getting these treatments approved, and supporting finding patients and diagnosis is the motivation for the team….Ultimately, what we are trying to do is bring truly game-changing medicines to patients with limited to no options. It all comes back to supporting disease awareness and diagnostic education to help ensure patients are appropriately identified.”
“The most meaningful aspect of our work is our ability to ensure the ongoing viability of therapies that other companies struggle to either maintain on the market or bring to fruition,” adds Heck. “Knowing that we are addressing fatal, genetic, pediatric rare diseases makes this the most meaningful work imaginable. It is the reason we all get up in the morning… Our legacy will be defined by the products we continue to add to our portfolio, as well as the advancements we achieve with our current therapies.”
Zevra’s McFarlane concludes: “What we do in this industry is not easy. We face more failures than successes, and that is the reality of developing therapies for rare diseases. But when you invest in people who are deeply mission-driven and passionate about the work, and you give them the support to be their best, it is remarkable what we can achieve together.”
