Quest for rare disease treatments drives researchers

The woman had many large, pale spots on her skin; her face was crooked; her bones were riddled with lesions; and she had gone through puberty at an early age. At the time, the cause of the syndrome was unknown, so Taylor and her colleagues were forced to treat her symptoms — with recurrent surgeries for bone deformities, for example — without addressing the underlying cause of the condition. Taylor wished she could do more to help.

Now she works at the Novartis Institutes for BioMedical Research (NIBR), where scientists are working toward treatments for more than 40 rare diseases. Her years in the clinic gave her an understanding of the impact rare diseases have on individuals and families — and for their cumulative prevalence. More than 300 million people suffer from one or more of the approximately 7,000 known rare diseases, and Novartis scientists hope to make a difference in some of their lives.

In her current role as global head of the NIBR Program Office, Taylor looks across the organization’s portfolio to ensure that projects are aligned with the overall research approach. In a recent conversation, she discussed the promise and challenge of rare disease research.

Definition of a rare disease

By definition, a rare disease affects just a small fraction of the population — fewer than 200,000 persons in the United States and fewer than 1 in 2,000 in Europe. Why does Novartis work on diseases that affect so few individuals?

Taylor: “It’s not a business decision. We follow the science and evaluate the unmet medical need when selecting projects, which often leads us to rare diseases. We typically focus on a specific molecular pathway, develop a compound that impacts the pathway, and then ask, ‘Which diseases are associated with dysregulation of the pathway?’ It’s very exciting to be working for a company that encourages you to go after a disease that makes sense, even if the potential market isn’t big.”

Why does the science often lead you to rare diseases? 

Taylor: “Some rare diseases have uniform underlying causes, with defects in a single molecular pathway to blame. Common diseases, on the other hand, tend to be more heterogeneous and mechanistically complex, with multiple pathways involved. If we test our drug in a rare disease with a single defective pathway, then we can see if it works as intended before expanding to common diseases where the pathway is one of multiple variables.”

You mentioned that unmet medical need factors into project selection at Novartis. Can you elaborate on that in relation to rare diseases?

Taylor: “Rare diseases were historically overlooked by pharmaceutical companies, and many of them still aren’t understood. There are relatively few approved treatments for them. We’d like to expand the therapeutic arsenal for doctors to use in helping patients. We concentrate on rare diseases that are debilitating where the scientific understanding is strong and where we believe new treatments could significantly improve the lives of patients with these diseases.”

Is there a danger of overpromising?

Taylor: “We have to be extremely careful not to overpromise. If it’s a devastating disease without an approved therapy, patients and their families get very excited about the prospect of a treatment. It’s important for us to convey the clinical research process, including the long timelines involved, and to make sure that patients understand there’s no guarantee that an experimental treatment will work. We can partner with patient advocacy groups — which frequently encourage participation in clinical trials — to help set expectations that match reality.”

How has Novartis adapted clinical trials to address the needs of patients with rare diseases?

Taylor: “Instead of asking patients with a rare disease to visit a separate contract research organization site to participate in a clinical trial, we work to integrate the research into their regular care. We find the experts in a particular disease, clinicians who may or may not have experience in clinical research, and we provide them with infrastructure and training to set up a study site.”

What else can be done to facilitate clinical trials in rare diseases?

Taylor: “We need to do a much better job of characterizing the natural history of these diseases so that we can measure whether or not new treatments are working. Take McCune-Albright syndrome, the disease I encountered at Mass. General. The underlying cause of the syndrome was discovered in 1991, but we still have not found a treatment. If we did have a specific therapy, we would still need more information to figure out how to run a clinical trial. We don’t always know how quickly the average patient with a particular rare disease gets worse, making it difficult for us to determine if an experimental treatment is slowing the rate of progression. To run an effective clinical trial, we must be able to score success.”