Translational Science Highlight
- NCATS partnered with patient organizations to create a web-based platform of patient-focused rare diseases translational science resources, many of which also are applicable to other diseases.
NCATS is committed to engaging patients and their support organizations as essential partners in the therapeutics research and development process. To bolster these efforts, the Center partnered with members of the rare diseases community to create the NCATS Toolkit for Patient-Focused Therapy Development. The Toolkit is a platform of online resources to support patient groups seeking information about the process of therapy development and provides them with the tools they need to advance their research.
On Sept. 8, 2017, more than 230 patients, caregivers and other community members participated in the official launch of the Toolkit on the NIH campus in Bethesda, Maryland, and via videocast. In opening remarks, NCATS Director Christopher P. Austin, M.D., called the Toolkit the “crowning achievement” of NCATS’ commitment to involving patients in everything the Center does.
“NCATS recognized there were many effective, patient-focused resources on therapy development available and wanted to support the patient community by combining them into one accessible and user-friendly online resource,” said Petra Kaufmann, M.D., M.Sc., director of the NCATS Office of Rare Diseases Research, as she unveiled the live portal at the meeting. “It’s my sincere hope that our new Toolkit will help accelerate the path from discoveries to better treatments for our patients.”
Ronald J. Bartek, who co-founded the Friedreich’s Ataxia Research Alliance (FARA) after his son was diagnosed with the rare neurodegenerative condition, helped lead the Toolkit’s development with Annie Kennedy from Parent Project Muscular Dystrophy (PPMD). For nearly two years, they collaborated for with NCATS staff and a diverse range of other patient groups to identify and evaluate existing resources. The tools range from general guidance to educational videos to key scientific papers.
“This Toolkit initiative is for us, by us,” Bartek said.
Accelerating Early Discovery
One challenge in rare diseases research is the relatively small number of patients with the disease, who are often geographically dispersed. Patient registries help patients and families find one another, bring rare disease communities together and help them to connect with research opportunities. Through registries and natural history studies, researchers can follow a group of people with a specific disorder over time to learn more about a condition. Registries can also involve patients in the clinical studies and therapeutic development process.
Megan O’Boyle, who has a child with Phelan-McDermid syndrome (PMS), is the principal investigator for the PMS Data Network. She shared her experiences with launching the PMS International Registry for this rare genetic disorder that causes developmental delays, admitting that she didn’t know what a patient registry was when another parent first called to ask for help in establishing one. That request began a long journey that included contacting more than 30 other rare disease groups for advice and guidance. Today, the PMS registry is helping researchers and clinicians discover important insights about this condition.
“If I were starting from scratch, frankly, I probably would have hung up on the woman that called me,” O’Boyle admitted. “But today, I would go to this fabulous Toolkit,” she added while highlighting the “Starting a Patient Registry” resources on the Toolkit Discovery page.
Preparing for Clinical Trials
Another challenge in rare diseases research is that some pharmaceutical companies may be hesitant to take on the risk of developing a potential therapy for a condition that affects a relatively small number of people. NCATS and many patient organizations work to make therapeutics development less risky for industry and help develop the foundational science needed to prepare for clinical trials.
Jennifer Farmer, executive director of FARA, described how the alliance was well-poised to help when Reata Pharmaceuticals, Inc., approached them with a promising new therapy for Friedreich’s ataxia in 2014. FARA connected Reata with expert clinicians in its research network and facilitated early discussions. The alliance stayed involved in many aspects of the clinical trials for the therapy, such as determining which outcomes to measure in the trial and conveying why those endpoints were chosen to the U.S. Food and Drug Administration (FDA).
The Toolkit’s Preparing for Clinical Trials page has information on many of these activities, including how FARA led the development of an international network of clinical research centers.
Speeding Clinical Trials and FDA Review
Kenneth Hobby, president of Cure SMA — spinal muscular atrophy — discussed the essential role patients played in getting the first treatment for SMA approved by the FDA in 2016.
SMA, which leads to progressive muscle weakness, affects a wide range of patients from infancy to adulthood and leads to a wide range of severity in symptoms. Placebo-controlled clinical trials to evaluate a group of similar patients may, in some cases, be the best way to test whether a drug is effective. But it can be difficult to recruit and keep patients in these kinds of studies, since some of those accepted are randomly assigned to not receive the investigational therapy.
Cure SMA’s close-knit community, which emphasizes care and support as well as research, maintained support from parents for placebo-controlled clinical trials that only evaluated a narrow age range. While this was a tremendous sacrifice for some patients and their parents, the resulting strong data helped get the therapy approved more quickly. In turn, Cure SMA worked with the involved pharmaceutical company and the FDA to make sure the therapy was approved for use in all patients with SMA — from infants to adults — using additional data from other studies in the development program.
Information about participating in FDA meetings and recruiting participants for trials can be found on the Toolkit Clinical Trials and FDA Review page.
Improving Access and Affordability after FDA Approval
Although FDA approval of a treatment is often seen as the end goal, Kennedy emphasized that there is still a lot that patient groups can do once a therapy is on the market. She discussed PPMD’s efforts to ensure patients with Duchenne muscular dystrophy have access to and can afford the first two recently approved therapies.
For example, PPMD used data from its registry to conduct a burden-of-disease study. This type of study establishes how much it costs to live with a condition over a lifetime, including lost wages for caregivers and costs to modify a home environment. PPMD used these cost estimates when discussing with insurance companies how much coverage they will provide for the new treatments. Kennedy said these estimates are especially important to justify the high upfront cost of some treatments, such as gene therapies.
The After FDA Approval section of the Toolkit has information on conducting burden-of-disease studies, working with payers for reimbursement, creating therapy and care guidelines, and developing programs to speed diagnosis.
Strengthening the Patient Community
“Do not get overwhelmed: Get started!” was a major theme throughout the meeting. Participants agreed the Toolkit will help make taking those first steps easier and will energize them to make further progress. That was certainly the case for Beth McGinn, whose daughter has a rare leukodystrophy commonly referred to as LBSL — leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation.
“The Toolkit is exactly what I need,” said McGinn, whose foundation, A Cure for Ellie, is working with other families, researchers and clinicians to develop a mouse model that will be used to test drug therapies already being investigated in similar conditions. “We are nearing a stage where we will need to form a registry, so to have all that information in one place is super useful.”
Partnering with others in the community was another lesson of the day. For example, rare disease organizations with extremely small numbers of patients can partner with groups with similar conditions to pool their resources to make progress. The Toolkit can facilitate these connections and enable patient groups to learn from others’ successes — as well as missteps — to work faster and more cost-effectively.
“You have this cycle where newly diagnosed patients or their families reinvent the wheel over and over again,” said Sarah Hogate Bacon, a writer and patient advocate living with lymphangioleiomyomatosis. “To have a roadmap of all the steps that they can turn to is a real salvation.”
The Toolkit: An Evolving Site
NCATS and the patient community emphasized that the work was not over, and there was significant discussion about how the Toolkit could be improved or expanded. Attendees had plenty of suggestions for “Toolkit version 2.0,” such as adding information on repurposing existing drugs and how to ensure clinical trials include diverse populations. Still, suggestions for evolving the site did not detract from the consensus that the Toolkit initiative marked an important milestone for patient-focused research.
Matthew Toth, Ph.D., from the Barth Syndrome Foundation, summarized it well: “I’ve never seen anything like this before, and I think it has changed the way we look at how drugs are discovered, how they are going to be used and how they are approved in the future.”
Posted October 2017