Closing the Rare Disease Innovation Gap

For the 30 million patients in the U.S. with a rare disease and few treatment options, the low probability that any treatment will ever be available for them in their lifetime is daunting and at times devastating, as if the world has left them behind. Drug development for rare diseases can be exceedingly difficult, and patients are depending on policymakers, regulators and the scientific community to offer solutions. One possibility is greater use of the Accelerated Approval pathway.

The Food and Drug Administration recently approved a novel therapy for Duchenne muscular dystrophy utilizing this special pathway when the science is imperfect but the disease is deadly. We support the approval but also note that the development program left many questions unresolved. Given the severity of the disease, the data obtained and the demonstrated safety of the product, the FDA made a difficult but correct decision that could encourage increased use of the Accelerated Approval pathway while maintaining FDA’s strong standards for safety and science-based decision making.

The decision to approve eteplirsen as a treatment for DMD was not without substantial ongoing controversy within the FDA and among the public. Rare disease drug development is one of the most risky, complex, and challenging scientific endeavors in the world of biotechnology. Duchenne drug development has been notoriously difficult for serious biological reasons with genetic muscle diseases. Due to low disease prevalence and limited information about disease characterization, progression and evaluation, conducting Duchenne or any rare disease studies can be extraordinarily difficult relative to traditional clinical trials. To counter these challenges, we need to use new methods of evaluating rare disease treatments including biomarker tests or, as used in the Duchenne case, muscle biopsies that measure important biomarkers of disease. Biomarkers are compounds found in the body such as a blood, X-ray or muscle biopsy test that can be used to precisely measure disease activity and, in some cases, the impact of a treatment.

The increasing role of patient experience and risk preferences as another key input in the drug development process is particularly important for making a decision regarding an accelerated approval. There were many challenges in the eteplirsen development program but in the end, the balance tipped toward approval and Janet Woodcock, who leads drug review at FDA, made a difficult decision, but one which we support.

The use of disease-specific biomarkers can improve the speed and efficiency of treatment development, but for rare diseases, qualifying a biomarker has been extremely difficult. For patients with DMD, a biomarker protein critical for proper muscle function called dystrophin is very deficient in muscle samples and increasing its level was the key measure that played an important role in the approval decision of eteplirsen. The clinical study was small, and other methodologic issues created concern about the veracity of the results. The safety and the benefit: risk preferences of patients were also factors that should play into these difficult decisions.

For other diseases, the Accelerated Approval pathway has been largely underutilized due to lack of guidance on how to qualify new biomarkers for use in drug development programs. Thought leaders in the advocacy community have been calling for additional guidance on behalf of the patients and researchers who wish to accelerate the pace of medical innovation. We believe that patients with rare diseases deserve a chance of receiving a treatment in their lifetime. For many, the Accelerated Approval pathway represents their only hope.

The old models of developing medicine have served us well, providing breakthroughs in cancer, diabetes, and heart disease, but if we are to solve the challenges posed by rare diseases, we must use novel approaches and ensure regulatory agencies demonstrate flexibility in decision making. In fact, in 2012, Congress signed into law legislation that provides the FDA the authority to consider novel approaches to drug development, especially in cases of rare or ultra-rare diseases. This shift in thinking will be essential in closing the innovation gap that currently exists for the patients still waiting for a treatment.


Emil Kakkis, M.D., PhD, is the founder and president of the EveryLife Foundation for Rare Diseases (Novato, Calif.), a nonprofit organization dedicated to accelerating medical innovation for patients with rare diseases.

Max G. Bronstein, MPP, is the senior director of advocacy and science policy at the EveryLife Foundation for Rare Diseases.

Morning Consult welcomes op-ed submissions on policy, politics and business strategy in our coverage areas. Submission guidelines can be found here.

Morning Consult