The Importance of Drug Development for Rare Diseases

FDA defines rare diseases as “a disease or condition that affects less than 200,000 people in the United States”. 1 The development of treatments for these diseases has unique challenges that can lead to a lack of options for patients. PharmTech spoke with Elisabeth Gardiner, PhD, chief scientific officer of Tevard Biosciences, about these challenges and what makes treatments for these conditions so important.

Because rare disease treatments target a small number of people, there can be little return on investment for pharmaceutical companies. This can be set off by incentives given by regulators and governments,2 but it’s still can be a gamble for some companies. Gardinar suggests that a therapeutic approach that can be applied to multiple rare diseases may create the opportunities companies are looking for that can also help additional people.

“The ironic thing is that when drug hunters think about looking at targets for new drug discovery projects, they really look to rare diseases to get hints for targets and for this deep underlying biology that might be really interesting and exciting,” Gardiner says. “An example of this is PCSK9 inhibitors. They were originally found by looking at familial hypercholesterolemia that was actually quite rare. Homozygous familial hypercholesterolemia was discovered in the 1930s. This observation has yielded not only Nobel Prizes, but some of the most successful drugs that we have. Really understanding the work that was decoded by Brown and Goldstein, you know, that work earned them the Nobel Prize. That was on LDL [low-density lipoprotein] receptor mutations, and essentially, these genetic insights led to the development of PCSK9 inhibitors that can dramatically lower LDL. And in fact, there's even a genetic, medicine now, being brought forward by Verve. It's a CRISPR-based editor. It essentially, it can address familial hypercholesterolemia, but the way it's working in the clinic, it may be applicable to anybody with hypercholesterolemia. It's incredibly exciting.”

References

1. FDA. Rare Diseases at FDA. FDA.gov. Nov. 21, 2024. https://www.fda.gov/patients/rare-diseases-fda
2. FDA. Designating an Orphan Drug Product: Drugs and Biological Products. FDA.gov. August 12, 2025. https://www.fda.gov/industry/medical-products-rare-diseases-and-conditions/designating-orphan-product-drugs-and-biological-products

About Elisabeth Gardiner, PhD

Elisabeth is chief scientific officer at Tevard Biosciences, joining the leadership team in 2025 to spearhead the company’s pioneering tRNA-based gene therapies for rare diseases with high unmet need. With more than 25 years in the biopharmaceutical industry, she has directed and managed drug discovery and development efforts yielding 11 IND filings, four Phase I/II trial candidates, and one Phase III candidate. Prior to Tevard, Elisabeth held senior R&D leadership roles at Tactile Therapeutics, Alterome Therapeutics, Aravive, and Kinnate Biopharma, where she directed multidisciplinary teams and advanced programs from discovery to clinical-stage development across neurology, oncology, and rare disease. Elisabeth gained experience in tRNA biology while working at aTyr Pharma and at Scripps Research Institute in the lab of Paul Schimmel. Elisabeth’s commitment to the ethical development of effective and accessible medicines is her key focus in life. In addition to her professional work, Dr. Gardiner acts as a patient advocate in the rare disease and oncology space. Elisabeth earned her Ph.D. from the University of Wisconsin-Madison and holds a B.S. and an M.S. from Texas A&M University.

Transcript

Editor's note: This transcript is a lightly edited rendering of the original audio/video content. It may contain errors, informal language, or omissions as spoken in the original recording.

Hi, I am Elisabeth Gardner. I'm CSO of Tevard Biosciences. There is a significant unmet medical need to address rare diseases. Given the challenges in developing treatments, especially disease-modifying treatments for rare disease, it's critical to be able to have an approach that can efficiently target multiple rare diseases.

I think that part of the problem is, you know, when you're going after a single rare disease, you don't actually get as much, bandwidth, much addressable population. So, if you have a therapeutic approach that can actually address multiple rare diseases, potentially rare diseases with the same sort of underlying genetic mechanism, then you really have an excellent opportunity to help a lot more people.

And I think rare diseases are very poorly named. It's only rare until it's your loved one that has the rare disease, and then all of a sudden you realize that you're part of this club that you really didn't want to be part of, and you're suddenly part of a really large community of people that are desperate for answers and desperate for cures.

The ironic thing is that when drug hunters think about looking at targets for new drug discovery projects, they really look to rare diseases to get hints for targets and for this deep underlying biology that might be really interesting and exciting.

An example of this is PCSK9 inhibitors. They were originally found by looking at familial hypercholesterolemia that was actually quite rare. Homozygous familial hypercholesterolemia was discovered in the 1930s.

This observation has yielded not only Nobel Prizes, but some of the most successful drugs that we have. Really understanding the work that was decoded by Brown and Goldstein, you know, that work earned them the Nobel Prize.

That was on LDL receptor mutations, and essentially, these genetic insights led to the development of PCSK9 inhibitors that can dramatically lower LDL.

And in fact, there's even a genetic, medicine now, being brought forward by Verve, Verve one oh one. It's a CRISPR-based editor. It essentially, it can address familial hypercholesterolemia, but the way it's working in the clinic, it may be applicable to anybody with hypercholesterolemia. It's incredibly exciting.

I think thinking about rare diseases, they provide insights for the larger population, but, I mean, there's just a huge unmet need. There's so many rare diseases out there.

There are three main challenges that I think everyone working on rare disease encounters. One is the lack of reliable models, either animal models or cellular models. Two is the complex biology of the disease, and three is the lack of funding. So many rare diseases do not have a cellular animal model that can permit drug screening or testing to be done in a way that's actually translational to the human condition.

It's tough, actually, to know if one cell line that is available or one mouse model that you might have access to is going to be representative of the human pathology that you're trying to treat.

It's a really black box. I mean, it's a lot of guessing. It's expensive and time-consuming to actually develop the models that are most relevant, and money and time are often in very short supply when you're trying to be innovative, and certainly, the patients can't wait that long.

One of the reasons why rare disease, medications take so long to get to the clinic is because we have very specific guidelines about how we bring drugs to the clinic, and part of that is, you know, we need a cellular model, we need an animal model, we need to do the toxicity testing, and then we can put it in humans.

I think all of that is, is really important, but when you talk about rare disease, you really need to think out of the box. I love actually what the FDA is doing right now. They're really trying to streamline the process for rare disease. They're well aware that the animal models may not be there.

They're focused on cell model development, and in fact, there's a whole coalition that's kind of working on not just thinking about how to move rare disease medications forward, but really thinking about how to build the cellular models, how to build the pediatric models, that, that might be key for, for getting things, into the clinic without having to build the animal models. And so, changing that timeframe, you know, changing that delay.

So, for rare disease research and development, the lack of funding is really a tricky thing. I think often this comes because of the complex biology of the disease, so investors may be loath to jump into investing in something that has such complex biology.

They look at it, and they think: "That's gonna take a long time for me to get return on my investment." And I think that's logical.

But when, when you think about it, you know, genetic diseases are not just one thing. It may be just one gene that is the causative gene that's making the pathology relevant to the patient, but often you're not dealing with a simple situation.

So that one genetic malformation may cause a whole cascade of biological problems, and so you're dealing with a potentially very fragile patient population.

And so that's another reason why people may have difficulty, actually getting into rare disease biology and thinking about it from a drug discovery perspective.

Often, patients are on another type of drug to manage symptomology, and this can actually mask the benefit of a potential new medication. It may actually exacerbate the condition, too.

So, for example, you may be on a genetic therapy that's very helpful to cure your disease by modifying the gene, but if that genetic therapy is causing liver damage, that could kill you. And so, you may have a patient that ultimately could be helped, but ends up having an exacerbation that leads to a lifetime of illness, unrelated to the original genetic cause.

So, I think that there's a lot of problems, you know, this sort of, this thought process that I have, you know, this one mutation that's caused me to have epilepsy.

But all of my organ systems are now disturbed because my epilepsy has actually damaged my brain, and so that could be GI issues, that could be verbal issues, that could be issues responding to other medication because brain chemicals are changed by the constant inflammation.

There's a lot of reasons why the complex biology of the disease just makes rare diseases very tricky, and that gets to the lack of funding. So, it really takes a lot of money and highly trained people to make a rare disease treatment work well.

One example, quite recent, that was highly successful was the Baby KJ story. This was highly publicized. It was truly a tremendous scientific effort for one baby, you know, with one rare disease. And stories like this catch the attention and, you know, really fill people with a lot of hope and excitement.

But the reality is that this took a tremendous amount of money and a tremendous amount of effort, and I would say altruism, on the part of a large number of people.

If you look at the paper, there's a lot of names, you know, on the author list, but everybody behind that, you know, this kid's parents, all the caregivers, all the nurses, therapists, rehab folks, everybody who worked with this kid, and, I mean, he didn't spend one night at the hospital.

He spent a long time at the hospital trying to make sure that the therapy was working and actually working through any, potential ramifications of the genetic, medication that he got.

I was so impressed when I read this because what a tour de force, right?

But a success story like this really hammers the point home that this is big business. I mean, it requires a lot of money to work efficiently. They took so little time to get that done, and honestly, the FDA worked with them in a tremendously efficient way.

But when you're an investor, you think, "Okay, that's just one patient. How am I going to get return if I throw millions of dollars at this? Will I be getting millions of dollars back? Will I be getting billions of dollars back? Is there that big a market?"

I think that the way that we can think about this is, you know, a lot of times you think, "Well, I can charge three million dollars for a single treatment," but when you're the patient, or the patient's family, and, or an insurer, and that's your option, you may not be very interested in that. I mean, that may be out of reach.

And so, I think that we need to be able to think long term and think about expanding out from the original patient population into the broader population, similar to the PCSK9 story. You know, from an investor standpoint, understanding how much return on investment you're going to get is a really sensible question. But I think it's important to be creative and having a real understanding about the complex biology so that you can expand and show the investors that we'll treat these 10 patients or maybe these 100 patients, but this potential therapy can be broad spectrum.

You know, we can really look across a lot of disease states if we can actually tackle this one disease state.