Many MDF community members are aware of an important, multi-year MDF effort -- MDF 3.0: Accelerating Drug Development -- because we published an article on the launch of this initiative in early 2015.

As you may know, the goals of MDF 3.0 are to:

• Strengthen capacity and infrastructure in DM clinical care to drive more accurate clinical trial design, improve capacity to evaluate drug efficacy and advance understanding of disease course
• Deepen and strengthen the research and development bench to drive more myotonic dystrophy discoveries
• Expand the drug development pipeline with additional pharamceutical partners, additional translational research and more critical data
• Incentivize investment in myotonic dystrophy via key studies, data collection, industry partnerships and a targeted and immediate advocacy effort with federal agencies and legislators

Below is a first-year report on how elements of MDF 3.0 got launched and how we are doing to date.

1.   Expand the Fellowship Program

First launched in 2009, MDF's Fund-a-Fellow (FAF) program was designed to:

• Attract new investigators to the field of myotonic dystrophy (DM) research
• Increase interest and activity in the field of myotonic dystrophy research
• Expand knowledge and understanding of DM
• Increase the number of labs and academic programs engaged in or expanding their engagement in DM research

To date, MDF's FAF Program has funded seventeen postdoctoral research students, providing over $1,700,000 to DM research focused on enhancing the quality of life of people living with DM and advancing research focused on finding treatments and a cure for this disease.  

And for 2016, an unprecedented six new fellows have been funded, who are pursuing research projects ranging from understanding the cognitive effects of DM to making a mouse model of DM2.

2.  Conduct a Prevalence Study

A major objective of MDF 3.0 is to determine how common the DM1 and DM2 mutations are in the general population. Many have quoted the figure “1 in 8000” as the “prevalence” of myotonic dystrophy—that is, how many people may have the disease at any given time—but this number comes from studies done in other countries, and it also relies on diagnosed cases of DM. Given that the diagnostic odyssey can take as long as 14 years in myotonic dystrophy, it is likely that diagnosed cases represent the tip of the iceberg.  

An accurate understanding of the occurrence of DM in the population, both diagnosed and undiagnosed, is a fundamental building block for efforts to improve treatment resources and develop a cure for DM. In 2015 MDF released a “Request for Applications” to fund the first of a two-part project to understand how common these mutations are in the population.

In October, MDF announced that funding for the first phase of this project will go to Dr. Nicholas Johnson at the University of Utah. Dr. Johnson will focus on making sure that he can scale up his diagnostic testing method to process 50,000 or more total samples at a reasonable cost.  

In the next phase of the project, which will be announced in the spring of this year, MDF will invite investigators to submit their plans for screening a random sample of the population for mutations that cause DM1 and DM2. Results are expected in early 2017.

3.  Create access to tissue samples 

Early in 2015, MDF began hearing from members of industry that they were having difficulty obtaining biological samples, particularly cell lines, from people with DM that they could use to identify drugs that might be developed into therapies.

To help address this problem, MDF partnered with Orig3n, a new biotechnology start-up company that is specializing in creating cell lines from rare disease patients. Under a memorandum of understanding (MOU) between MDF and Orig3n, the company came to the 2015 MDF Annual Conference and drew blood from approximately 50 volunteers. The company intends to create cell lines over the next 12 months. The majority of Orig3n samples are from current Myotonic Dystrophy Family Registry members and can be tracked to their registry records anonymously through a unique identifier number, providing useful additional information about the cell line donors.   

MDF is working with Dr. John Day’s group at Stanford University and other investigators with biobanks to raise visibility and promote more community and researcher participation in them.

4.  Drive drug discovery through an assay development and screening project 

In June MDF issued a Request for Applications to help identify possible new drugs for myotonic dystrophy. This led to collaboration between academic investigators with in-depth DM knowledge and industry and industry/government entities with drug development experience and scale-up capabilities.

A panel of experts in drug screening and therapy development reviewed the proposals submitted and chose the team that will receive a $200,000 award over the next year. The successful applicants will be announced in the next issue of the DM Research News.

5.  Accelerate identification of appropriate DM biomarkers and clinical endpoints

Biomarkers and clinical endpoints are different ways of measuring changes that occur as a consequence of a disease, over the course of a disease or in response to an intervention.  A biomarker is typically evidence of a physiological change that has occurred, often detected in blood or tissue samples, that is relevant to the disease process. A clinical endpoint is some way of measuring how a patient “feels, functions or survives.”  

Biomarkers that provide early evidence that a drug is working are crucial for making drug development economically feasible. This is especially true for diseases that progress relatively slowly, like DM.

Biomarkers are also useful in creating better trials (by selecting people with DM who have specific characteristics for trials or making sure those characteristics are balanced in the different groups that make up the trial).  

MDF held a meeting in Fall 2014 to explore the status of biomarkers and endpoints for myotonic dystrophy, addressed biomarkers at the FDA regulatory workshop in the Fall of 2015 and will issue a Request for Applications in Spring 2016 to provide support for the development or refinement of biomarkers for myotonic dystrophy.  

In addition to the need for biomarkers, the need to identify an appropriate primary clinical outcome measure for new therapeutics is becoming an urgent priority as the DMPKx phase I/II clinical trial moves toward completion.   

The primary clinical endpoint is the test that will be used by the Food and Drug Administration to determine if an experimental treatment actually works. For example, a clinical endpoint could be the time it takes someone to get up from a chair and walk 30 feet, or it could be a person’s score on a survey about the severity of his or her symptoms. The scientific community has proposed various endpoints.  

In November 2015 MDF released a request for applications to support projects to develop new endpoints for myotonic dystrophy or to further refine endpoints already in development. Successful applicants must demonstrate how they will work closely with FDA staff to ensure that the work will be useful from a regulatory standpoint. Successful applicants will be announced in late Spring 2015.

6. Federal Advocacy

Regulatory Advocacy

As part of the three year 3.0 effort, MDF launched a significant advocacy effort targeting US congressional leadership, federal agencies involved in the drug review and approval process, agencies leading research investment and policy, and international bodies with impact and influence on the drug development and approval processes. 

MDF hosted the first-ever meeting of stakeholders involved in drug development to look at the regulatory pathway and better understand how potential DM therapies will be reviewed and assessed by the Food and Drug Administration (FDA), the European Medicines Agency (EMA) and others. More than 80 participants from academia, industry, the FDA and other federal agencies joined MDF in September 2015 to review progress toward the development of biomarkers and endpoints for DM clinical trials, the design of clinical trials, and to hear feedback and information from the FDA to help guide their drug development efforts. 

As a part of that meeting, MDF also contracted with Silicon Valley Research Group to conduct the first-ever benefit-risk study for myotonic dystrophy potential therapies, to introduce first-phase information on what therapy benefits are most important to DM patients and what risks patients would be wiling to accept for those benefits. The findings from this study were presented at the FDA workshop at the suggestion of the FDA. 

Because the patient perspective is becoming increasingly important in the overall drug development and approval process, this benefit-risk study will be followed with other MDF efforts to present the patient voice and perspective to the FDA and other regulatory and federal bodies in the months ahead.

The meeting helped industry get current thinking from the FDA, and was followed by a half-day workshop of just industry and academic participants to discuss what they heard, explore common areas of potential partnership or barriers to progress. MDF is working with a professional science writer to finalize a draft publication of the proceedings from the all-day workshop, and plans to submit it for publication in early 2016. 

Legislative Advocacy

In early 2015 MDF hired a public policy firm in WA, DC to help define and deliver a comprehensive strategy to drive Care and a Cure through 2017. A key recent effort involved crafting report language and direction that will be proposed for insertion into the 2016 US federal budget to influence research investment and other policy work that is important to the DM community. MDF also engaged the team to bring congressional leadership to the first-ever legislative briefing MDF held on Capitol Hill in conjunction with our 2015 MDF Annual Conference and Hill Day, and to develop the materials used to educate Congress about critical DM issues. MDF will continue this work in 2016 with outreach and education efforts with key congressional leaders and additional grassroots and grasstops advocacy work in partnership with the MDF community.

Federal Agency Advocacy

People living with DM often struggle with the application process for Social Security disability benefits. MDF investigated and then met with the Social Security Administration (SSA) to explain the issues we experience and how the SSA can improve the process and outcomes for people with DM. MDF staff, DM physician Dr. Ami Mankodi and DM community members (Larry and Hunter Lord, and Loraine Dressler) participated in the meeting.

MDF will build on this work with education programs for the 2,500 SSA staffers who review claims in the field, and will create a Toolkit for community members to make the application process easier.

MDF also attended a number of Muscular Dystrophy Coordinating Committee (MDCC) meetings, applied for a position on the MDCC coordinating committee, supplied several rounds of proposed edits to the current MD CARE Act Action Plan (which the MDCC oversees), and held partnership meetings with key federal agencies including the National Institute of Neuromuscular Disorders and Stroke (NINDS) and other National Institutes of Health (NIH) agencies that influence the advance of DM science and research funding.

Grassroots and Grasstops Advocacy

MDF built on its first ever grassroots advocacy efforts in 2014 with a second Hill Day, bringing more than 80 community members to Capitol Hill to educate legislators and their staff on issues important to the DM community.  This work will expand significantly in 2016 with one-on-one meetings with key policy makers.

In short, 2015 was a great kick-off year for MDF 3.0, and we look forward to more high-impact work in 2016. We will keep you apprised.

Questions?

Please contact MDF. We would love to hear from you.