Dr. Vivian Cheung is in the relatively unusual position of being a rare disease researcher who lives with a rare disease. In many professions, personal experience in a field only strengthens expertise — but for scientists, clinical investigators and physicians, the perception can be a little different.

“I think in medicine and in science, there's this idea that people should be perfect, and that somehow spills over into the idea that people should also be physically perfect. It makes people very unwilling to disclose a disability,” said Cheung, a pediatric neurologist and professor of pediatrics at the University of Michigan who heads up the Vivian Cheung Lab there.

“We somehow want to be different from the patients that we care for, which really is too bad,” she said.

Cheung has a very rare mutation of the LTBP4 gene that has affected her vision and balance. She’s also experienced firsthand the challenges that come with such a diagnosis in a way most scientists and physicians do not.

She filed a discrimination lawsuit against the Howard Hughes Medical Institute after the research organization declined to renew her contract in 2018 when she was diagnosed. The trial is scheduled to start December 4. A Maryland Circuit Court recently denied HHMI's motion for summary judgment. Cheung’s team, which studies “the shape and structure of RNA and related rare diseases, mostly neurologic diseases that affect children,” discovered differences in RNA-DNA sequences beyond what was already known.

“My lab studies how the sequences of RNA affect the function. We used to think that DNA is just kind of the blueprint of everything, so when we go from DNA to RNA to protein, all the sequences are the same. But my lab found that the RNA actually are much more complicated,” she said. “The sequence and the structure of RNA are really important because we cannot make medicine out of RNA unless we know the sequence and the shape of those [RNA] arms.”

However, in some ways, perceptions of Cheung’s disability have overshadowed her work. In getting diagnosed, one of her medical procedures accidentally left her with a spinal cord injury, requiring her to use a wheelchair for a little over a year.

As a result, Cheung had trouble commuting back and forth between Maryland, where she was establishing a project for children with ALS with collaborators at the NIH, and her lab at the University of Michigan. Eventually, Cheung said HHMI offered her medical retirement.

She said HMMI “told me that I should accept the offer for medical retirement.” She wasn’t even 50 years old at the time.

“I did not accept their offer to retire — I went up for the renewal, and they did not renew,” she said.

A spokesperson for HHMI said in an email that “the record clearly supports our position that Dr. Vivian Cheung’s allegations have no merit.” The organization employs a “rigorous process” of peer review for appointment renewal that includes written submissions, an oral presentation and an assessment of scientific accomplishments and breakthroughs, the spokesperson said. “HHMI believes strongly that science needs to be inclusive of scientists from all backgrounds and perspectives, including scientists with disabilities.”

Firsthand experience

Cheung has transitioned many of her patients into wheelchairs over the course of her career as a pediatric neurologist, but never really understood what that meant in a practical sense until she started using one herself.

There are challenges, of course, like discrimination and physically navigating inaccessible spaces, but also subtler things like “getting used to society looking at us differently.”

“I still remember showing up at work the first time in the chair and all of the eyes that fell on me,” she said, adding that she had to learn to “deflect those eyeballs … knowing that the person in the chair and the person standing up is the same person.”

Yet for all the struggles that come with having a rare disease and disability, it has also offered her professional advantages.

“I think it makes me understand much more acutely why it is so important to understand a disease,” she said. “Instead of it just being a career, I … am closer to my patients because I understand the day-to-day.”

She feels the same way about her work as a researcher.

“Compared to that younger version of me, I certainly am much more focused, and I feel that urgency to solve problems,” she said.

An industrywide issue

Cheung’s experience highlights a larger issue within academia and research: a lack of disability representation.

Increasing diversity in the life sciences is a buzzy topic, and rightly so. But disability often seems to be forgotten in that conversation, both when it comes to clinical trial participation and the researchers themselves.

“As a scientist with a disability, I certainly have to work harder … to prove I deserve that seat at the table,” she said. “It's hard to be a woman, a woman of color and have a disability.”

New research in the journal PLOS Global Public Health is calling for a “diversity factor” to evaluate scientific journals and research papers. This metric considers the demographics of the researchers who perform studies, as well as the patients who participate in them.

Today, most researchers are white, male and from wealthy countries, the authors noted.

“What happens when all of the authors involved in a project are alike is that they’re going to have the same blind spots. They’re all going to see the problem from the same angle,” co-author Leo Anthony Celi, a senior research scientist at MIT’s Institute for Medical Engineering and Science, said in a statement. “What we need is cognitive diversity, which is predicated on lived experiences.”

They’re also mostly able-bodied, and even the new “diversity factor” doesn’t explicitly mention disability.

The value of lived experience extends to disability, but Cheung notes it’s difficult to determine how many scientists and researchers are in that boat, especially since many people are afraid to disclose their disabilities.

The numbers that do exist, though, paint a bleak picture. Cheung points to one study showing that just 1.2% of NIH grant applicants had principal investigators who reported a disability. As many as 27% of adults in the U.S. have some type of disability.   

In filing her lawsuit and advocating for herself, Cheung wants “things to change for scientists with disabilities,” especially since she often sees students and trainees with disabilities questioning whether they belong and even leaving to pursue other fields.

“I think that having us in the biomedical field is really important,” she said. “I am hoping that this will give us a chance to think about what really can be done so we can truly have a more diverse biomedical workforce.”

The U.S. rare disease market is cultivated by a set of regulatory incentives like the Orphan Drug Act and others that allow pharmaceutical companies to reap the benefits of aiming at targets with very small patient populations. Many pharmas are taking the bait, which is good for patients and adds up to a quickly growing segment of the life sciences sector.

It comes down to this: While each rare disease is only present in a small number of patients, about 10% of the U.S. population is afflicted with one of these diseases. With 30 million Americans and many more globally suffering from rare conditions, the market is wide and deep, accounting for more than 700 medicines in the biopharma pipeline.

AstraZeneca, one of the leaders in the space, saw rare disease drug sales contribute $7.1 billion to its revenue total in 2022, growing 10% from the previous year. Pfizer has a strong pipeline of rare disease candidates with 10 currently in the clinic, three of which are late-stage gene therapies, and executives have cited the space as a major contributor to future growth.

The global rare disease treatment market reached more than $195 billion in 2022, according to a report from GMI Insights. With a conservatively estimated compound annual growth rate (CAGR) of more than 8.5%, GMI expects the market value to reach $435 billion by 2032. Other reports in the past have estimated the decade's CAGR to surpass 12%.

That growth is less of a surprise when considering how wide open the rare disease space really is. With more than 7,000 rare diseases and 400 million people affected by them worldwide, about 90% of these conditions have no treatment, according to another rare disease leader, Roche.

New approaches

Plenty of rare disease research happens outside of the Big Pharma realm, but with the growth of the market, giant drugmakers are bringing some of their assets in through M&A. AstraZeneca's $39 billion purchase of Alexion in 2021 is one of the biggest in recent years. Amgen's $28 billion acquisition of Horizon Therapeutics sent the M&A watchers abuzz as the largest merger of the year in 2022.

And while companies like Pfizer have been pushing into this rare disease market growth through their pipeline, the company has also pivoted to a more nuanced approach to the wide and unfocused area.

"We have rethought our approach to rare disease and will move from having a standalone research unit to aligning key programs with other therapeutic areas," said Dr. Mikael Dolsten, president of worldwide R&D and medical at Pfizer, on the company’s most recent quarterly earnings call. "We plan to externally advance rare disease programs that do not fit into a core therapeutic area of focus — at the same time, we plan to tap into the expanding external innovation ecosystem by actively pursuing biotech innovation and emerging innovation that fits strategically and accessing external assets that are differentiated."

Fueling the growth of rare disease research is the faster pace of innovation and lower costs of genetic solutions. For example, the cost of genomic sequencing has fallen from billions of dollars for a single human genome in the early 1990s to less than $1,000 currently. Genetic conditions account for about 80% of all rare diseases, according to a report from IQVIA.

A long-term study of the FDA's orphan drug program found that 5,099 treatments were granted the designation between 1983 and 2021, and each decade grew stronger, more than doubling in each era. About 37% of these were for oncology, 13% in neurology and 9% in infectious diseases. Across rare diseases, almost a third were granted for pediatric designations.

"The dramatic rise in overall orphan designations over the past four decades suggests we may continue to see an upward trajectory in designations leading to an increased number of approvals for drugs and biologics designed specifically for diagnosing, preventing, and treating rare diseases in the coming decades," wrote the authors of the 2021 article published in the Orphanet Journal of Rare Diseases.

Despite seismic growth in rare disease drug development and regulatory approval, the space isn't without challenges, mostly around the notion of patient access and pricing. Gene therapies in particular, which present a potential cure for rare diseases, also come with a hefty price tag — every gene therapy approved in the U.S. has become the most expensive drug in the world upon the regulatory go-ahead.

Although obstacles remain in the rare disease sector, the market forces that drive innovation and patient care appear strong and poised for further growth in the coming years.

Life sciences companies are leaning into the rare disease space, with the market expected to grow at a compound annual growth rate of 12.8% between now and 2030. Still, more than 90% of the 7,000 known rare diseases lack a treatment option.

And, as the industry is all too aware, there’s no silver bullet for filling these gaps. Despite the increased investment, numerous roadblocks along the drug development pipeline continue to hamper efforts to bring therapies to patients.

In a recent PharmaVoice poll, industry leaders were divided over where the biggest barrier to rare disease drug development lies — designing and enrolling patients in clinical trials, pushing treatments through regulatory approvals or launching the drug into the market.

Recently, regulatory and research advancements spurred by COVID-19 have helped overcome some of the most glaring obstacles to rare disease drug development.

Clinical trial concerns

With restrictions on in-person clinic visits during the pandemic, pharma companies were forced to think outside the box and utilize decentralized trial approaches and real-world evidence to keep research flowing. Once the infrastructure kinks can be worked out, these new techniques could provide a more effective framework for designing rare disease clinical trials with small patient populations

According to Hassan Kadhim, senior director and head of clinical trial business capabilities at Bristol Myers Squibb, DCTs could allow companies to recruit more patients in trials because “they don’t have to be geographically located with the different sites.”

Similarly, Will Maier, the vice president of rare disease at ICON, told us in August that real-world evidence can be used to supplement the small patient cohorts that participate in rare disease trials.

“In rare disease, where you might not have much in the way of patient numbers or where diagnosis might be quite difficult, we often will just look at medical records to figure out who the patients are,” Maier said. “Sometimes those registries evolve into a post-approval safety study that is used as part of the condition of approval.”

Regulatory requirements

Operation Warp Speed allowed the federal government to accelerate the development of needed vaccines and therapeutics at the onset of the COVID-19 crisis. The same tactics implemented through that initiative could soon be applied to expedite the approval of rare disease medications, Dr. Peter Marks, the director of the FDA’s Center for Biologics Evaluation and Research, told attendees of the 2023 Biopharma Congress.

Among the regulatory challenges drug developers face in the rare disease space is collecting enough evidence in small population clinical trials to show efficacy and safety, and then communicating the information quickly with regulators.

In October, the FDA announced a pilot program to help sponsors address these problems and better determine endpoints to assess the efficacy of a drug. Under the Rare Disease Endpoint Advancement (RDEA) Pilot Program, the FDA will accept one proposal for an active pre-IND or IND for a rare disease and will conduct ongoing meetings with the sponsor to evaluate the endpoint. Eventually, findings from the program could be used in an agency guidance document or workshop to improve the industry’s overall understanding of rare disease endpoints.

Additionally, Marks said the FDA hopes soon to “allow the clinical development (of rare disease drugs) to happen in constant communication and sharing of potential results before a submission of an NDA or BLA. That’s the idea — to move things as fast as possible.”

Market viability

Rare disease treatments that make it to launch often come with a hefty price tag. For instance, CSL Behring’s gene therapy Hemgenix for hemophilia B was approved in November and given a $3.5 million price tag.

While the high list prices aren’t likely to change, companies and governments are searching for better financing mechanisms to reduce out-of-pocket costs for these types of medications. Some of the innovative methods include voucher programs, value-based pricing, public-private partnerships, patient assistance programs and targeted grants. In the case of Bluebird Bio’s Zynteglo for the blood disorder beta thalassemia, which entered the market last year with a list price of $2.8 million per treatment, the biotech opted for an outcomes-based pricing approach, meaning it will refund up to 80% of the drug’s cost if it is not effective for the patient.

Still, as patient healthcare costs rise, developing new financing models to improve patient access to rare diseases is likely to become more important for both governments and private entities. 

Much attention has been paid to orphan drug rules in recent years as regulators and pharma work to get more rare disease medications to market. But as of late, the FDA’s approach to exclusivity has proved a key sticking point.

After over a year, the FDA last month broke its silence on how it intends to review orphan drug exclusivity in light of a 2021 appeals court decision that rebuked its longstanding approach to the issue. But the new clarification likely won’t give much peace of mind to rare disease drug developers in limbo over how to navigate exclusivity. That’s partially because the agency isn’t changing its approach — and it could see even more litigation over exclusivity in the next few years, according to attorneys.

In its 2021 Catalyst Pharma., Inc. v. Becerra decision, the U.S. Court of Appeals for the 11th Circuit found that the FDA’s policy of applying exclusivity to the uses and indications for which a drug is approved, rather than the entire disease area, violated the original intentions of the Orphan Drug Act. Specifically, it held that by greenlighting Jacobus Pharma’s treatment for the autoimmune disease Lambert-Eaton myasthenic syndrome (LEMS) in pediatric patients, the agency breached the orphan exclusivity it had previously granted to Catalyst Pharma for a similar treatment in adult populations.

Until last month, the FDA stayed quiet on the ruling and even delayed deciding on pending orphan drug exclusivity applications in hopes that Congress would deliver a legislative fix to codify its interpretation of the statute. When lawmakers failed to pass such a measure, the FDA said in a Federal Register notice it would comply with the Court’s decision in Catalyst, but “in matters beyond the scope of that court order,” intends to continue applying the narrowly focused, indication-based approach for orphan exclusivity.

And while the announcement lends much-anticipated clarity to how the agency will move forward with orphan drug approvals, it has surfaced more questions about the policy’s legal future.

“People will be looking at this issue very closely and those people that are adversely affected — either (because) FDA approved somebody when another company was already granted orphan exclusivity, or the FDA denies approval based on this — you've got companies on both sides and they're certainly going to sue FDA over this” said David Rosen, a partner at Foley & Lardner.

On one hand, FDA has said its approach is intended to incentivize the continued development of medications for all people affected by a rare disease even after a drug has been approved for one population. But some argue that the circuit court’s more expansive view of the law could make orphan drug exclusivity more valuable by giving drugmakers assurance that they could recoup their investment in the larger patient population. Whichever way the law ultimately lands could have broad implications for how pharma companies approach rare disease drug development.

Uncertain ground

On the surface, the FDA’s announcement makes clear the agency will apply its historical interpretation to all future orphan exclusivity cases. However, in light of the Catalyst decision, its interpretation of the statute now also stands on shakier legal ground, especially in Alabama, Georgia and Florida where the 11th Circuit’s decision is legally binding.

Therefore, companies with narrowly defined exclusivity for an orphan drug could use the Catalyst ruling to challenge the agency’s approach. So, although the FDA’s view of exclusivity is firm now, future legal cases could once again throw it up in the air.

At the same time, the agency could seek legislative reforms to the Orphan Drug Act to prevent these future lawsuits. Although FDA Commissioner Dr. Robert Califf said during a recent fireside chat hosted by the Alliance for a Stronger FDA that this one of “the smaller fixes” he’s hoping to accomplish, it’s unclear if the measure would pass in a divided Congress.

In the meantime, Rosen said it’s important for rare disease drug developers to account for the potential uncertainty such lawsuits could bring by ensuring their drug applications cover specific patient populations. He also suggested drug developers try to “tease out FDA’s position” on the indications and extent exclusivity could be granted but warned that such conversations could also turn out fruitless.

“FDA generally won't talk about anything doing with respect to exclusivity, until the product is ready to be approved or is approved,” he said.

Future legal challenges

While future litigation is anticipated, the facts of any case used to challenge the FDA’s interpretation of exclusivity will matter a great deal. Catalyst, for instance, came about 40 years after the Orphan Drug Act was created because of confusion over whether a pediatric indication could truly be considered different from an adult indication.

“It's just that FDA’s interpretation in this one impacted somebody, and it hasn't been a clear cut, close decision in the past,” Rosen said.

For a future case around exclusivity to spark, similar questions about whether two drugs approved for different indication areas actually treat the “same disease or condition” would need to arise.

Litigants could “be looking at stages of disease, for example, and whether that's going to be enough,” Rosen said. “If I get approval for a product in stage one and you want to go for approval in stage four, is that the same indication?”

Money will also come into play. Rare disease drugs target small patient populations, and companies that might consider suing the FDA over exclusivity will need to consider whether going through lengthy, expensive litigation is worth the reward. At the end of the day, Rosen said its “all a matter of timing,” when it comes to a company’s decision to forfeit cash for the extra years of exclusivity they might have left.

Still, Rosen and other attorneys have suggested it’s not a matter of if future litigation against FDA’s orphan exclusivity interpretation will pop up — but when and where.

If a similar case to Catalyst lands at another circuit court, and if that court rules differently than the 11th Circuit, the issue could even wind up in front of the Supreme Court, Rosen said, adding that whatever happens, “it's going to be interesting in the next few years when the next case in this situation comes up.”

Researchers in any field know that careers are forged not necessarily from once-in-a-lifetime "eureka" moments but from a series of iterative observations that add to a body of work — discipline, patience and perseverance are the key to scientific discovery.

For Sindhu Ramchandren, director and clinical leader of neuroscience at Janssen, keeping that perspective is especially important in developing drugs for rare diseases, where a community of patients await breakthroughs that take time and commitment from a core group of devoted minds.

"I think the eureka moments come, but they are few and far between. It's very easy to get emotional because you see the community and it's very easy to hope for the best," Ramchandren said. "But as a scientist, those moments where you say, 'I'm seeing a signal,' can only come at the end when you're looking at the vast majority of data altogether."

Ramchandren turned a fascination with neurology and how specific parts of the brain impact certain parts of the body into a career in the rare neuromuscular space. Patients with diseases like muscular dystrophy, myasthenia gravis and chronic inflammatory demyelinating polyneuropathy (CIDP) have been her specialty since her days in academia at the University of Michigan and as director of a clinic for rare neurology.

"I always was very privileged to take care of these individuals with a lot of life lessons learned from them — how they handle diversity and how they maintain hope that there is something coming in the future that will improve if not for them, than others with this disease," Ramchandren said. "That's something I always carry with me."

And today, she carries those lessons into the drug development arena, leading clinical programs to treat neurological diseases like myasthenia gravis with a therapy called nipocalimab, which is designed to block receptors that lead to the miscommunication between nerves and muscles.

Harnessing the immune system

Janssen showed in a mid-stage clinical trial that nipocalimab significantly improved symptoms in patients with myasthenia gravis, which is associated with trouble walking, swallowing, breathing and sight. This is a result of autoantibodies that form in the spaces where the brain speaks to the muscles, causing the patient's own immune system to disrupt those signals.

"The body starts recognizing itself as foreign — in myasthenia gravis, what happens is that the immune system forms autoantibodies that target muscle proteins that are responsible for communicating with the nerves," Ramchandren explained.

The standard of care for a disease like myasthenia gravis or CIDP is currently broad immunosuppression, which comes with many side effects. Drugs like steroids or those used in chemotherapy can also take a long time to start working. And suppressing the immune system can leave a patient vulnerable to infections and other risks.

"About 20% of patients with myasthenia gravis don't respond to the current standard of care, so there's an unmet need where we need something that's more specific and faster," Ramchandren said.

Nipocalimab, on the other hand, is not an immunosuppressant but rather an immunomodulator. Thus, patients who cannot tolerate a weakening of the immune system — elderly, pediatric or pregnant patients, for instance — might have a better chance with nipocalimab.

For Janssen, which has a deep pipeline in neuroscience, nipocalimab represents not just a chance to treat patients with one or two rare diseases, but potentially a wide range of diseases including hemolytic diseases of fetuses and newborns.

"The specific opportunity that Janssen saw with nipocalimab was that it could be a very unique product to address multiple rare diseases simultaneously," Ramchandren said. "Pharmaceutical companies have many options out there for them to say, 'What should we go after?' and I think the unmet need in rare neurology and the fact that this molecule could address so many different diseases was very attractive."

Rare disease roadblocks

Challenges in addressing rare diseases are numerous, and one of the greatest hurdles is in diagnosing and finding patients. Not every disease has a biomarker that can be pinpointed. In patients with myasthenia gravis, there is often an autoantibody present, but not in all patients, Ramchandren said. What's more, a general physician does not always know to look for the rarer indications of the disease. Thus, it can take years for a correct diagnosis.

Beyond these challenges, Ramchandren said that development considerations for rare disease drugs, such as a disconnect between a trial design and what patients need, are so complicated they can limit investment.

"There's not a very good algorithm to take those calculations into account," Ramchandren said. "So there needs to be a larger discussion beyond showing what is effective in a clinical trial to looking at the endpoints that the rare disease community really wants us to be looking at, and how to show the value to the larger group of stakeholders to bring these drugs into the market."

In studying nipocalimab for myasthenia gravis, Janssen explored not only the levels of autoantibodies but also a measure of daily living that indicates symptom severity. Both improved in the phase 2 study.

The pharma giant is enrolling a late-stage study in adults with myasthenia gravis. Two ongoing mid-stage nipocalimab studies include those in pediatric patients with myasthenia gravis and adult patients with CIDP.

"As a physician, this is such an exciting time for autoantibody diseases that we have these new mechanisms," Ramchandren said. "We're really excited and hopeful about the future of public health."

When Tamar Thompson’s husband was diagnosed with prostate cancer, she knew better than most what kinds of testing and care he’d need. As vice president and head of corporate affairs at Alexion, AstraZeneca Rare Disease, Thompson is intimately familiar with the healthcare world. And as a decorated officer in the United States Air Force, her husband should have received the best, most cutting-edge care.

Despite all these advantages, Thompson still struggled to get her husband the genetic testing she knew was available.

“I had to fight for that. It wasn't offered right up front,” she said. “I don't know that it would have been (like) for someone who was non-African American. But I know that for him, I had to fight for a number of things. And thank goodness I work in the space to know what to ask for. But I saw the misses along the way.”

Thompson even pulled her husband out of their local health system for fear that he wouldn’t get adequate care as a Black man.

These challenges — including lack of access, missed care and subpar treatment at small or rural hospitals — are common healthcare experiences for people of color.

They’re also common for rare disease patients, and Thompson sees those parallels every day.

For instance, some rare disease patients live in rural communities without access to an academic medical center, she said, and that’s true for minority patients, too.

“Black and brown patients generally can't travel more than a 50-to-75-mile radius from their home,” she said.

They often face similar financial hurdles, too.

“Rare disease patients may live on one income, often because one person has had to give up a job to be a caregiver. And that's very similar to some of the challenges you see in the minority communities as well,” she said.

Those parallels are some of the reasons why Thompson was drawn to working with the rare disease patient population at Alexion.

An unconventional path

A rare disease biopharma company that was acquired by AstraZeneca in July 2021, Alexion has five approved medications for seven rare diseases, including the blockbuster first-in-class C5 complement inhibitor Soliris (which was, at one time, the most expensive drug in the U.S.), and the second-generation C5 complement inhibitor Ultomiris. Its pipeline also consists of potential medicines for more than a half dozen rare therapeutic areas, including hematology, neurology, cardiology, nephrology, bone metabolism, metabolics and ophthalmology. 

Thompson leads the government affairs and policy and communications functions for the company, working to amplify the voices and experiences of rare disease patients, advocate for needed policy changes, create access opportunities for patients and partner with rare disease organizations.

Prior to joining Alexion in 2019, she worked as the head of federal executive branch strategy and state government affairs for Bristol Myers Squibb. However, her path to healthcare policy was much more unconventional.

At first, Thompson studied nursing, but soon realized that she wasn’t quite suited for it. Sticking a needle in someone’s arm and telling them, “Suck it up, buttercup? That probably isn't the best bedside manner,” she laughed.

Instead, she shifted her focus to healthcare administration and the revenue cycle side of healthcare, eventually pivoting to the life sciences and policy advocacy. But it was working at Bristol Myers Squibb that first exposed her to the rare disease community and opened her eyes to the parallels between the experiences of rare disease patients and the healthcare inequities that minority communities face.

For instance, she notes that it often takes rare disease patients roughly five years to get a diagnosis, and that missed or delayed diagnoses are also common among ethnic minorities. Such diagnostic disparities are well documented in academic research, from dementia, to autism spectrum disorder, to appendicitis, to breast cancer and many other conditions.

Too often, health complaints of people in the Black community — especially Black women — are dismissed, Thompson said. In fact, she had a close family member who died from a disease because they didn’t get a diagnosis until it was too late.

That’s why, when she had the opportunity to move to Alexion and advocate on behalf of the rare disease community, she took it.

“It felt really aligned and parallel with my family journey, with what I've seen in my community, so I was drawn to it,” she said. “I've never looked back. I'm still loving every minute of it and appreciating the opportunity and the privilege that I get to come in every day and search for disease patients.”

Rare disease progress

Now, as the U.S. commemorates the 40th anniversary of the Orphan Drug Act, as well as Rare Disease Day later this month, Thompson is reflecting on how far rare disease treatment has come — and how far it still needs to go.

“We can point to more than 500 unique therapies that have come through the pathways under the Orphan Drug Act,” she said. “I think the Orphan Drug Act is really an example of when you get policy right, it can be a motivator and a simulator for innovation, and it's good for patients at large.”

However, she expressed concern that certain provisions within the new Inflation Reduction Act (IRA) could inhibit future progress in rare disease research.

Although the National Organization for Rare Disorders called the IRA “a significant step forward in helping ensure that individuals and families with rare diseases have access to the comprehensive health care they need to survive and thrive,” Thompson said provisions within it undermine part of the Orphan Drug Act.

Part of the IRA allows the CMS to negotiate the prices of certain Medicare and Medicaid covered pharmaceuticals and biologics. However, orphan drugs that are indicated for “only one rare disease or condition,” are exempt from price setting, which could discourage companies from studying products for secondary or tertiary conditions. 

“We have drugs that are useful for multiple disease states: One therapy, but useful for multiple rare diseases. We wouldn’t fall under the exemption for that under IRA,” Thompson said.

Still, she remains hopeful about the future of rare disease treatments and health equity for all patients.

“If you look across industry at what's in development, 40% of that is rare by some definition. So that’s promising for a community with more than 7,000 unique rare diseases and roughly 5% (that have) approved treatment options,” she said. “If you're telling me that 40% of the pipeline in development is touching that, that is a call for excitement and enthusiasm within itself. That means hope and promise.”