How patient registries contribute to the development and approval of new therapies for orphan drugs. 

Contributed Commentary by Eric Gemmen

July 8, 2016 | When developing a new treatment for a rare disease, the first thing developers should do is build a patient registry for their target patient population. Rare disease patient registries are online platforms where patients and caregivers record information about their diagnosis, condition, and treatment experience. These platforms give developers a mechanism to gather valuable insights that will shape their research and help them demonstrate effectiveness to regulators and payers as part of the approval process.

Setting a Baseline

Ideally, developers set up these registries as a first step in their research process. Starting early (e.g., while the product in development is in Phase I or Phase II trials) enables them to build out a robust population and gather meaningful baseline data on the current state of the disease and the impact of existing treatments (if any). They can use this data as a control group against which to compare future trial results, which, in turn, can eliminate the need for a placebo arm and provide demonstrable proof of improved quality of life.

This early data can also help registry developers validate the choice of primary and secondary endpoints for clinical trials, which is critical in rare disease studies where meaningful endpoints can be difficult to define. For many of these diseases, endpoints are often related to functional improvements, such a six-minute walk test—used to evaluate progress among patients with Duchenne muscular dystrophy—or extended life expectancy rather than definitive biomarkers to demonstrate efficacy.

This results in a more streamlined research program, giving researchers greater access to potential trial recruits, and more confidence that their trial design is aligned with the needs of patients, regulators, and payers.

We have already seen many biotech companies pursuing these registries in an effort to optimize their rare disease programs. True North Therapeutics, a clinical stage biotechnology company, recently launched the COMPASS Registry in collaboration with PatientCrossroads to support its efforts to develop novel therapies for Cold Agglutinin Disease (CAD), for which there are currently no approved therapies available. Executives with the firm say the COMPASS Registry will provide them with deeper understanding of the natural history of CAD, help them characterize clinical biomarkers, and engage early with patients and physicians to accelerate development of new therapeutics.  

“The COMPASS Registry is a leading example of how a patient registry can serve as an important and powerful tool for collecting data on a defined group of patients who share a particular disease,” Kyle Brown, CEO and Founder of PatientCrossroads, a registry developer, said in a statement. The registry will enable the researchers to collect data about the disease and to foster greater collaboration with patients and physicians to improve clinical outcomes.

Support For Approval

Once a rare disease trial is launched, the patient registry continues to contribute valuable data to the research process while giving developers a channel to communicate with patients and caregivers to drive improved engagement with the research.

Over time, the collection of real-world results allows researchers to explore quality of life changes in patients using the drug and to make comparisons among patients on different treatment regimens or who have varying genetic backgrounds or co-morbidities. They can also track adherence to the drug and the occurrence and impact of side effects. All of this data can be used to support label claims and pricing requests, giving regulators added proof that a drug meets safety and efficacy requirements of regulators and effectiveness demands of payers.

In some cases, this research has been shown to be a deciding factor for regulators considering a submission. In 2003, for example, the European Commission authorized an expanded indication for Cerezyme (imiglucerase, Genzyme) to include Type 3 Gaucher disease, the chronic neuronopathic form of the disease. This decision was reached thanks in large part to data generated from the Gaucher Registry, which has been tracking clinical outcomes for 2,500 Gaucher patients worldwide since enzyme replacement therapy was introduced in 1991.

And in 2010, Myozyme (alglucosidase alfa, Genzyme), was approved by the US Food and Drug Administration (FDA) as the first treatment for patients with Pompe disease on the basis of two studies with historical controls where the Pompe Registry was used to create a subgroup-matched historical control based on certain prognostic factors.

Tracking long-term results

Even after a rare disease drug receives commercial approval, registries can continue to offer vital data to demonstrate that the ongoing benefits of the drug outweigh its risks. This is a common requirement for rare disease drugs, especially those that have received accelerated approval and/or rely on smaller clinical trials to demonstrate safety and efficacy.

One such example is Myalept (metreleptin for injection, Aegerion), which was approved in 2014 as replacement therapy to treat the complications of leptin deficiency in patients with lipodystrophy. As part of the approval, FDA is requiring a Risk Evaluation and Mitigation Strategy (REMS) that includes gathering data through a long-term product exposure registry of patients to assess for the immunogenicity, and to track reports of serious risks related to its use.

Start early, stay connected

Building a patient registry requires additional time and resources, but the long-term benefits are clear—especially for rare disease research where any supporting patient information adds value to the process. Investing in a registry at the outset of a development program enables researchers to understand the disease journey, test research questions and gather data to support their label claims, all of which can speed the approval process. And when you are developing a drug for which there is likely no other viable treatment, such speed can save lives and improve the quality of life of patients around the world.

Eric Gemmen is senior director of epidemiology, Quintiles. He can be reached at Eric.Gemmen@Quintiles.com.