Accelerating Breakthrough Discoveries into Medicines

BioMotiv Blog

Developing Treatments for Rare Disease

By: Erin Reese

February 28 is Rare Disease Awareness Day – an international day of recognition to raise awareness about rare diseases and the impact they have on the lives of patients and families. Here at BioMotiv, our mission is to accelerate breakthrough discoveries into medicines for the patients who need them most. Very often, those patients are living with one of more than 7,000 identified rare diseases — many of which have no available treatment.

I recently sat down with BioMotiv’s Chief Medical Officer, Jeff Edelson, MD, to learn more about what goes into developing treatments for rare diseases.

Jeff Edelson, MD

Jeff Edelson, MD

What are some of the challenges in developing a treatment for a rare disease?
Development of therapies for rare diseases often requires exploration of novel or unprecedented molecular targets and pathways, an absence of validated cellular or preclinical models of the disease, and, generally, no clinical or regulatory agreement regarding the definition of what a clinical benefit would look like in a relatively small patient population.

Can you describe the typical process for developing a treatment for rare disease?
Drug developers in this space need to precisely define the group of patients who might benefit from the proposed therapy and undertake an in-depth understanding of what causes the disease and its progression to identify biologically valid, potential targets for therapeutic intervention. The early drug development team will attempt to identify agents that can potently and selectively engage the target with the goal of restoring normal function. The potential agent will be tested in pre-clinical studies to define its safety, tolerability and activity in restoring function and treating the disease. Later clinical studies explore the drug’s safety, tolerability, and efficacy in defined patient populations. Testing in humans is especially challenging when the disease population is very small or is comprised of individuals incapable of  providing informed consent due to age or mental incapacity.

Despite the progress that has been made in rare disease drug development, it’s important to note that the process takes time. The journey from identification of the genetic abnormalities underlying Cystic Fibrosis to understanding the cellular and tissue abnormalities in the disease, to development of targeted therapies took over 20 years.

What role do patients and patient advocacy organizations play in the process?
Patients are key partners in any drug development program. This role is especially important in drug development for rare diseases. The development of patient advocacy efforts, beginning with well-informed groups of patients who are able to articulate their views and preferences, provide input on their perception of clinical benefit, development programs, study design, and, importantly, inform discussion of clinical trial endpoints and outcomes that are important to them, have all helped development of deep and meaningful collaborations involving patients, pharmaceutical sponsors and regulatory bodies. Such dialogue is essential for successful planning and execution of clinical studies. Patient involvement also allows for realistic discussion and calibration of potential benefits and harms, and helps resist the potential for individual patient coercion in studies of diseases with very high unmet need.

In addition, disease-focused organizations have developed registries of rare patient populations that inform the understanding of the natural history of the condition and may be used as historical comparisons when defining signals of drug activity early in drug development and registrational programs. The National Organization for Rare Disorders provides  powerful, informed, integrated, advocacy, organizational and policy resource for  patients, patient organizations, industry, clinicians and legislators. The development of venture philanthropy capabilities, with the access to state-of-the-art capabilities in drug development (for example, the CF foundation) has accelerated the availability of therapeutics for specific populations of interest.

What drew you to work in the rare disease space?
My personal interest in rare disease drug development stems from the ability to focus on conditions characterized by high unmet medical need despite available therapy, in addressable patient populations. As a pulmonologist, sequential and rapid scientific and clinical developments in therapies for cystic fibrosis has added decades to the median survival of such individuals and inspired translational research approaches for other rare diseases. It is exciting to join with a diverse group of industry experts, patients, regulators, and other stakeholders in this journey.

Erin Reese