MDF’s Interim Chief Science Officer Dr. John Porter knows firsthand what it takes to develop rare disease therapies, from basic research all the way to clinical trials. His wealth of professional experience – as a former academic researcher, a program director at the National Institutes of Health (NIH) and the CEO of a patient advocacy organization – makes him uniquely suited to further our mission of Care and a Cure for myotonic dystrophy (DM).
We spoke with John to find out more about the importance of patient advocacy in driving treatment development.
A New Partnership Model for Drug Development
MDF has a critical role to play in forging partnerships between the DM community, pharmaceutical companies, academic institutions, and funding organizations like the NIH, says John.
Gone are the days of academic researchers toiling in isolation, while commercial drug developers independently pursue a parallel track. Researchers on both sides of the aisle need each other, and they need the patient community even more, says John. MDF is uniquely positioned to bring these players together for the benefit of all, and the DM community in particular.
“No single entity has all the resources to make it happen” when it comes to developing new therapies, John noted. "It requires partnerships among all the players in the field, especially for rare disorders like myotonic dystrophy"
Leading the Way to Drug Trials
“We have to be a leader on trial readiness,” John says.
Reducing the risk that drug companies face in developing rare disease treatments is one way that advocacy groups like MDF can take the lead. For example, proving that a compound targets a specific disease mechanism and causes measurable changes in a mouse model can make the difference between a drug company’s agreeing to develop a treatment or not.
John points to DM1 therapy development as an example of partnering and “de-risking” done right. In 2009, Dr. Charles Thornton, a DM researcher at the University of Rochester in New York, and colleagues, published a paper in the journal Science showing that treatment of mice with a disease resembling type 1 DM (DM1) using a compound called an “antisense oligonucleotide” had potential in treating the disease.
The project, which had been funded by both the NIH and patient advocacy organizations, showed that the antisense strategy reversed many of the damaging molecular effects of the DM1 genetic flaw, and also reduced myotonia (difficulty relaxing muscles after use) in the mice. The success of the mouse project, and the cachet that public and non-profit funding provided, attracted the attention of drug developers Ionis and Biogen and ultimately led to the first trial for a DM treatment.
Another critical piece of trial readiness is developing meaningful and measurable endpoints to accurately judge the effects of an experimental treatment. Clinical trial networks that do this work are a major selling point for drug developers and grant providers, like the NIH. “This is a huge part of what we have to do,” John says.
The Myotonic Dystrophy Clinical Research Network (DMCRN), funded by MDF and other organizations, includes six medical centers with significant proficiency in DM care and research, all of which can work together to carry out a large-scale DM clinical trial.
“It doesn’t make sense for each company to reinvent the wheel on, say, an endpoint,” John says. Endpoints and other measurements, as well as the general “natural history” of a disease like DM, are often referred to as “precompetitive space,” in that they are difficult to achieve by any one group but can be readily adopted by all who develop drugs. Precompetitive space tools, like endpoints, are best developed with leadership from groups like MDF, and then made available to all companies working in DM.
Potential molecular and physiological endpoints are in place for IONIS-DMPKRx and being tested in an early-stage clinical trial by Ionis and Biogen through the DMCRN. The molecular endpoints are changes in the splicing of specific messenger RNAs in response to the drug, and a physiological endpoint is the degree of myotonia of muscles, measured by an electromyogram (EMG). Later, John notes, functional endpoints (such as stabilization or improvement in mobility) will be necessary before IONIS-DMPKRx or any other DM drug can be approved by the U.S. Food and Drug Administration (FDA). Identifying and validating those endpoints has to be a high priority goal.
Community Power in Action – Taking Part in Something Bigger
Of course, at its roots, a patient advocacy group is made up of patients and their families. It’s the power of this community that gets things done: raising funds, participating in clinical trials, and advocating for DM with Congress, the NIH, the FDA, and even medical students and doctors in training. John encourages all community members to attend the 2016 MDF Annual Conference where MDF will host a patient-focused drug development meeting so affected families can share their perspective with the FDA.
“It’s a powerful and critically important opportunity for the FDA to better understand myotonic dystrophy, which will enable them to better advise companies, and we’re going to have a better chance of getting drugs approved,” he says.
This opportunity to share treatment concerns with the FDA was a direct result of action taken by MDF. In 2015 the FDA began to seek input from patients on drug treatments through its Patient-Focused Drug Development (PFDD) Initiative. Myotonic dystrophy wasn’t included in the original series of disease-focused meetings, so MDF submitted a comprehensive Letter of Inquiry (LOI) in late 2015 to request one. MDF is now hosting the first-ever FDA Externally-Led PFDD meeting in September 2016, and you are invited.
The financial support of patient advocacy groups often makes the difference between a project’s success or failure, a phenomenon that John saw play out numerous times during his decade managing grants at NIH. “Some of the big therapy development grants that were funded through me while I was at the NIH would encounter snags at particular points, where other money was needed, John says. “Patient advocacy groups were able get an early stage projected started or jump in later and keep a project like the antisense for DM1 study going until it got to a point where industry would take it and run with it.”
“I feel that my most important role is as a facilitator, to see opportunities and challenges and help leverage the resources and expertise that allow others to succeed,” John says. “I feel pretty good if I have a small role in something very big happening.” At MDF, he says, “That’s what I’m trying to do.”