MDF Advocate Has Impact

The Peer Reviewed Medical Research Program (PRMRP) consumer advocate Glen Wiggans, MD recently participated in the evaluation of research applications submitted to the PRMRP sponsored by the Department of Defense. Glen was nominated for participation in the program by MDF. As a consumer reviewer, he was a full voting member (along with prominent scientists) at meetings to help determine how the $330 million appropriated by Congress for Fiscal Year 2018 will be spent on PRMRP research.

Ensuring the Patient Voice in Grant Review

Consumer reviewers are asked to represent the collective view of patients by preparing comments on the impact of the research on issues such as diagnosis, treatment, and quality of life for a broad range of topic areas. When commenting on serving as a consumer reviewer, Glen said that, “I found this experience to be most enlightening. The scientific reviewers were very knowledgeable and participation on the panel provided insight into how scientific proposals are carefully evaluated for funding”.

Consumer advocates and scientists have worked together in this unique partnership to evaluate the scientific merit of research applications since FY99. Colonel Stephen J. Dalal, Director of the Congressionally Directed Medical Research Programs, expressed his appreciation for the consumer advocate’s perspective during the scientific review sessions. “Consumer advocates are an integral part of the CDMRP’s scientific review process. They provide a key ingredient to the review process, the patient’s perspective, which is real and urgent. The collaboration of Consumer advocates alongside the scientists’ subject matter expertise is a truly unique collaboration that is difficult to find in most medical research programs.”

Important New Federal Funding Source for DM Research

Scientists applying propose to conduct innovative research that has the potential to profoundly impact the development and implementation of medical devices, drugs, and clinical guidance that will enhance the precision and efficacy of prevention, diagnosis, and treatment across a wide range of disciplines. The PRMRP fills important gaps not addressed by other funding agencies by supporting groundbreaking, high-risk, high-gain research while encouraging out-of-the-box thinking.

More information about the DOD’s PRMRP is available here!

Thank you Glen!

Additional Funding Opportunities for Myotonic Dystrophy Researchers

MDF is thrilled to announce that myotonic dystrophy (DM) is now officially included as an eligible research area in the Fiscal Year 2019 Peer-reviewed Medical Research Program (PRMRP) of the U.S. Department of Defense. Legislation including the PRMRP, H.R. 6157, was signed into law on September 28, 2018.

PRMRP: a $300M Research Program

The PRMRP, part of the Congressionally-directed Medical Research Program (CDMRP), was launched to support a broad range of scientific and medical research, but only for diseases that are approved for inclusion in the program. The budget for the program is over $300M, and researchers involved in listed diseases may submit requests for funding.

Myotonic Dystrophy First Included in PRMRP in 2018

MDF and our community advocates worked for over 2 years to successfully list myotonic dystrophy as an eligible disease for PRMRP funding in the 2018 budget, and reached out to Senators Feinstein and Durbin to pursue listing in the 2019 budget as well. PRMRP disease listing has to be pursued and approved annually, and we are committed to an ongoing effort to maintain our eligibility for funding.

You Can Help!

Learn how you can help advocate with your congressional representatives for important projects like this. MDF will host an advocacy webinar and training on November 13 to provide updates on our current advocacy efforts and explain how you have a critical role to play in convincing congressional leaders to support our requests. Click here to register.

Thank You!

This critically-important research funding source would not be possible without the support and efforts of our Congressional champions, Senators Durbin and Feinstein, and our grassroots advocates across the country, who called and met with their congressional leadership. Thank you – you have made great things possible in myotonic dystrophy research!

Will Accelerate Discoveries in Myotonic Dystrophy and Related Genetic Diseases

The Myotonic Dystrophy Foundation (MDF) announced today that the U.S. House Appropriations Committee included a MDF led provision in the fiscal year 2023 Labor, Health and Human Services funding legislation (page 153) that will help establish a new Repeat Expansion Disease Initiative (REDI) at the National Institutes of Health (NIH) to increase federal funding for research on repeat expansions like myotonic dystrophy including new funding mechanisms across multiple institutes to support scientific discoveries that will lead to treatments and cures for myotonic dystrophy and related genetic disorders.

In related MDF research advocacy news, efforts continue to secure continued eligibility (sixth year in a row) for myotonic dystrophy research as part of the Department of Defense Peer-Reviewed Medical Research Program (PRMRP) and for a new myotonic dystrophy research funding line-item in the Congressionally Directed Medical Research Program (CDMRP). Advocacy continues as the Senate Appropriations committee considers their version of this legislation and a final bill that includes details on these programs are expected in the fall.

In the House report, the committee recognized the rapidly emerging science on DNA repeat expansions and cited myotonic dystrophy (DM1 and DM2) as being a paradigm for a class of diseases caused by repeat instability and toxic RNA. Based on the opportunity to advance new groundbreaking research, the Committee is asking NIH to establish a trans-NIH Repeat Expansion Disease Initiative (REDI) to increase federal funding for research on repeat expansions including new funding mechanisms across multiple institutes to support scientific discoveries that will lead to treatments and cures for myotonic dystrophy and related genetic conditions. Under the legislation, NIH is required to provide the committee with an update on these efforts in early 2023 as part of the President’s fiscal year 2024 budget justification.

Congressional report language provides more detailed guidance to departments and agencies than is provided in appropriations bills. The REDI provision reflects the final views of the House Appropriations committee and will take effect upon the start of the new fiscal year 2023 in October. MDF and our advocates are urging the Senate Appropriations committee to include identical language in their fiscal year 2023 report which is not yet finalized although companion Senate report language is not required for this initiative to move forward. MDF will be working with the NIH, Congress, and our research community help with the implementation of this exciting new research initiative. 

Repetitive sequences comprise most of the human genome and have been a major roadblock to obtaining the full sequence of the human genome. It was only recently that the NIH-funded T2T consortium was able to generate full, end-to-end sequencing of all human chromosomes, published in Science, in April 2022. These repetitive sequences are the source of over 50 (and growing) distinctive disorders caused by DNA repeat expansions. Myotonic dystrophy type 1 and 2 are repeat expansion diseases and have served as paradigms for a class of diseases caused by repeat instability and toxic RNA, which includes C9ORF72/amyotrophic lateral sclerosis/frontotemporal dementia, Huntington’s disease, and many common forms of dominantly inherited ataxia. Over the past several decades, researchers have begun to understand how these mutations drive pathogenesis in many of these diseases, but new repeat expansion diseases continue to be discovered, and the recent genome sequencing data described above provides a new roadmap for both normal and pathologic functions of repeats.

Myotonic dystrophy type 1 (DM1) and type 2 (DM2) are caused by a CTG repeat expansion in the DMPK gene and a CCTG repeat expansion in the CNBP gene, respectively. These repeats are typically present in <30-50 contiguous copies in healthy individuals, but can expand to hundreds or thousands of copies in patients. These expansions prevent cells in the muscles, heart, and brain from functioning normally, leading to symptoms of myotonic dystrophy. Affecting as many as 1 in 2,100 individuals, myotonic dystrophy is the most common form of adult muscular dystrophy and considered the most variable of all known conditions; however, there is currently no cure and there are no approved treatments.

While U.S.-based researchers at the University of Florida, University of Rochester, Stanford University, Emory University, Baylor College of Medicine, and others are making progress to study how repeat expansions disrupt healthy gene regulation and cause disease symptoms, federal funding and coordination have been limited. Recognizing the current exciting landscape in biomedical research, the recently completed full sequence of the human genome, and emerging broad interest in repeat expansion diseases among patient advocacy groups and basic scientists, the Myotonic Dystrophy Foundation and our Scientific Advisory Committee urges Congress and the NIH to establish a new trans-NH Repeat Expansion Disease Initiative (REDI) within the Office of the NIH Director to fund new research and accelerate scientific discovery in this important new field. 

For example, we believe new federal research investments in the use of short- and long-read sequencing, high-throughput/high-resolution imaging, high throughput DNA synthesis technologies, and use of patient-derived cell biological tools/reagents will help scientists to better understand how the repeating RNAs cause a myriad of symptoms in virtually all tissues of the body, including skeletal, cardiac, and smooth muscle, and tissues of the central nervous system. We believe that new investments in studies of DM pathogenesis and RNA regulation will accelerate efforts to identify treatments and eventually cures for DM and other related diseases. 

The Myotonic Dystrophy Foundation (MDF) was founded in 2007 by families seeking answers and support. The MDF mission is "Community, Care and a Cure,": We support and connect the myotonic dystrophy community; We provide resources and advocate for care; We accelerate research toward treatments and a cure. Through direct services, research, education, and advocacy, MDF empowers the DM community, improves access to effective healthcare, and eliminates barriers to drug development. MDF is the leading global advocate helping individuals and families navigate the DM disease process and is often the first resource contacted by newly diagnosed patients, their families, their social workers, and their physicians around the world.

To learn more visit: www.myotonic.org

Click here to learn more about MDF's advocacy efforts.

Learn more a

Beginning in September 2016, MDF met with senior officials at the Social Security Administration (SSA), both at their headquarters in Baltimore, Maryland and via conference call, as part of our efforts to improve the process of applying for Social Security disability benefits for people with myotonic dystrophy. As a result of many months of meetings with the agency, MDF is extremely pleased to announce that Social Security Commissioner Nancy Berryhill has agreed to add congenital myotonic dystrophy as one of three new conditions newly-included in the agency’s Compassionate Allowances program. Read the SSA press announcement here.

For individuals with congenital DM and their caregivers, this means we can eliminate much of the red tape involved in applying for disability status and successfully receiving benefits. The Compassionate Allowances program is designed to quickly identify serious medical conditions that very obviously meet Social Security's standards for disability benefits and expedite a favorable decision on benefits.

We have long recognized that navigating the Social Security disability benefits application process is long and difficult, and it can take many attempts to be successful. The MDF Social Security Admininstration Toolkit and our Warmline live phone support for SSA applicants are two ways that we have worked to improve our community's access to SSA benefits. 

The September SSA announcement is a major step forward in our efforts to improve the process for our community. This was a hard fought effort, but we know that more work remains to be carried out on behalf of other MDF community applicants. We will continue to work to improve the program for everyone in the DM community.

"We will not forget your faces or your stories. Please know that all of your efforts will make a contribution to making [the regulatory review] process go smoother when a new treatment comes to the FDA to be reviewed."  -Dr. Larry Bauer, regulatory scientist, U.S. Food and Drug Administration (FDA)

DM PFDD Meeting Report Submitted to FDA

As many of our community members know, MDF held the first myotonic dystrophy (DM) Patient-Focused Drug Development (PFDD) meeting with key senior leaders from the Food and Drug Administration (FDA) as part of the 2016 MDF Annual Conference in September 2016. The DM PFDD meeting, which was the first Externally-Led PFDD Meeting sanctioned by the FDA as well as the first PFDD meeting focused on DM, presented community member perspectives on the most burdensome and most prevalent DM symptoms and what affected individuals would consider meaningful benefit from future therapies.

Well over 200 community members, industry professionals, academic researchers and FDA representatives attended the DM PFDD meeting live and via the live stream MDF provided. FDA leadership including Dr. Janet Woodcock, who oversees all drug evaluation and research at FDA as the Director of CDER; Dr. William Dunn, who is the Director of the Office of Drug Evaluation 1 – Division of Neurology Products, the division that will review all DM therapies; Dr. Jonathan Goldsmith, Associate Director of the Rare Diseases Program, Office of New Drugs, CDER/FDA; Dr. Larry Bauer, a regulatory scientist in the Rare Diseases Program; and a number of additional representatives from the Office of Health and Constituent Affairs, the Office of Translational Sciences, the Study Endpoints team, and others also attended.

The final task in the DM Externally-Led PFDD initiative was the creation and submission of a Voice of the Patient Report (VOP) to the FDA with comprehensive results of the meeting, including a comprehensive summary of the meeting and discussions, detailed polling results, audience demographics, a listing of FDA participants and panelists, as well as a report on the Benefits/Risks Study MDF conducted with the Silicon Valley Research Group in 2015. MDF submitted the VOP to FDA in May 2017 for distribution to internal FDA leadership, dissemination to the Neurology Products Review Division for inclusion in the benefit/risk framework used to assess potential DM therapies, and to ensure that FDA decisionmakers understand DM disease impacts as described by those living with the disease, and what our community would find clinically meaningful from future therapies.

MDF thanks our PFDD panelists, FDA leadership who helped bring the meeting to life, and Ionis Pharmaceuticals for providing attorney and former FDA professional James Valentine as a consultant on the project.

Questions?

Contact Molly White at MDF via email or phone  415-800-7777.

Related Articles and Blog Posts

• DM PFDD Meeting - Bringing Your Voice to Therapy Development
• Help the FDA Review Potential DM Therapies
• Big Changes Ahead for the FDA Could Benefit MDF Dystrophy

The AHCA

In March, Republican Members of the U.S. House of Representatives’ Committee on Ways and Means and the U.S. House Committee on Energy and Commerce introduced legislation, entitled the American Health Care Act (AHCA), that would repeal and/or replace major parts of the Affordable Care Act (ACA). The ACA (also known as Obamacare) expanded health care coverage for more than 20 million vulnerable Americans and prohibited health insurance plans from discriminating against individuals with pre-existing conditions like myotonic dystrophy (DM). MDF is committed to advocating to help ensure that all persons with DM have affordable, comprehensive health insurance.

MDF Response and Your Opportunity to Act

MDF has reviewed the legislative proposal and identified significant concerns about how the proposed changes would limit access to affordable, quality health insurance coverage and vital medical care, especially for individuals living with rare, complex and costly conditions like DM. As Congress debates repealing and replacing the ACA, we urge our community to inform their elected Representatives and Senators to carefully consider any significant changes to health care and ensure that the interests of all Americans needing health care, especially those with special needs, including persons with DM and their families, are fully protected.

Potential AHCA Impacts to DM Families

The Congressional Budget Office (CBO) AHCA Cost Estimate released on March 13, 2017, estimated that, in 2018, the AHCA legislation would change the number of people who obtain federally-subsidized health insurance through Medicaid, the nongroup market and the employment-based market—an estimated 14 million more Americans would be uninsured under the AHCA legislation than under the current ACA law.

The Congressional Budget Office estimates that the AHCA would tend to increase average premiums in the nongroup market prior to 2020 and lower average premiums thereafter, relative to projections under current law. Medicaid enrollees, according to the CBO estimates, would decrease by $880 billion over the 2017-2026 period, as the result of lower enrollment culminating in 14 million fewer Medicaid enrollees by 2026. Under the legislation, beginning in 2020, the federal government would no longer share in the open-ended financing of Medicaid. The AHCA would establish a limit on the amount of reimbursement it provides to states, with states bearing all of the burden for increased costs. 

Specifically, MDF is concerned about the following AHCA provisions:

• Insurance Subsidies. For individuals and families seeking health insurance who do not have group-based/employer-based coverage, AHCA would provide tax credits that would vary on the basis of age (not household income) between $2,000-$4,000 for individuals (more families) that could be used to purchase health insurance. These tax credits will be significantly lower than those currently offered under the ACA and could make it more difficult for lower-income individuals and families to afford health insurance. 
   
• Continuous Coverage Penalty. The AHCA requires nongroup or small-group market health plans to impose a substantial late enrollment fee (a surcharge equal to 30 percent of their monthly premium for up to 12 months) for individuals who reapply for coverage after going more than 63 days without health insurance coverage. 

The likelihood of having interrupted coverage is greater for those changing jobs, including people living with DM who may change or lose employment due to the significant physical and cognitive impairments. The AHCA thereby penalizes individuals with DM and other chronic conditions.

• Medicaid Expansion & Caps. Under the ACA, many states expanded eligibility for Medicaid coverage that was supported by additional federal funding. This would end in 2020 under the proposal, and many individuals currently receiving Medicaid coverage would lose coverage. Medicaid currently requires coverage for persons who qualify based on their income and their disability status. 

MDF is concerned that eliminating expansion funding and capping the federal contribution to state Medicaid programs could result in persons with DM losing coverage, and those who keep their Medicaid coverage could see a reduction in covered medical services and higher out-of-pocket costs. 

• Age Rating Rules. Beginning in 2018, AHCA would increase the limits on how much insurers in the nongroup and small-group markets can vary premiums on the basis of age. For example the premium for a 64-year-old could be three times to five times higher than the rate a 21-year-old is charged. This could adversely affect the adult-onset DM population.

MDF is pleased that the AHCA retains the following ACA provisions:

• Pre-Existing Condition Protections. Health insurers would still be prohibited from denying critical insurance coverage to individuals who have a “pre-existing” medical condition like DM, heart disease, diabetes and cancer. 
   
• Young Adult Coverage. Parents could keep children up to age 26 on their health insurance policies. 
   
• Lifetime & Annual Caps. Insurers would continue to be prohibited from setting annual and lifetime limits on health insurance expenditures they cover.

Next Steps - Get Involved

MDF will continue to advocate in a bipartisan manner to help ensure that all persons with DM have affordable, comprehensive health insurance with access to high quality medical care and therapies. Since it is anticipated that AHCA will be amended as it advances on its legislative journey to become a law, we will continue to closely monitor the evolving bills and offer our expertise. However, it is imperative that members of the MDF community become actively involved in advocating for ensuring access to affordable quality medical care for individuals with DM in their local areas as ACHA will likely include greater state-based choices.

Questions?

Contact MDF for more information at 415-800-7777, or info@myotonic.org.

Thanks to the hard work and commitment of advocates from the MDF community and many others, the 21st Century Cures Act has just been signed by U.S. President Barack Obama. This legislation is designed to enhance the drug review process and accelerate the approval of therapies to treat and cure rare diseases like myotonic dystrophy (DM). Thank you to all of you who who met with your members of Congress during our annual Hill Days, wrote your congressional leadership during our 500 Voices Campaign and helped raise the profile of the Act in Congress.

Bipartisan Effort

The 21st Century Cures Act was a bipartisan effort that originated in the U.S. House of Representatives under the leadership of Energy & Commerce Committee Chairman Rep. Fred Upton (R-MI) and ranking member Rep. Diana DeGette (D-CO). The legislation is intended to improve the Food and Drug Administration's (FDA) regulatory review process and provide an additional $8.75 billion over 5 years to the National Institutes of Health (NIH), to help put the NIH on a path to long-term growth and continued investment in medical research.

Funding and Regulatory Impact

Among the many stipulations of the Act, it:

• Authorizes the CDC to create the National Neurological Conditions Surveillance System to better track neurological diseases;
• Authorizes $500 million over 10 years to accelerate regulatory review through the initiatives included in Cures (below);
• Requires the FDA to issue data upon approval of a product stating how patient experience data informed the review process and decision;
• Requires issuance of additional guidance on how to collect and utilize patient experience data as a patient-focused drug development (PFDD) tool;
• Establishes a pathway for review and qualification of biomarkers/drug development tools;
• Allows applicants developing products for rare disease to include data from previously approved submissions involving the same or similar underlying technology to accelerate development and delivery of rare disease therapies; and
• Extends the Pediatric Rare Disease Priority Review Voucher to Sept. 30, 2020, and allows issuance of vouchers through 2022 if a designation for a candidate therapy was provided before Sept. 30, 2020.

Thank you!

Together we have made a difference! Thank you for all you do to drive Care and a Cure for DM!

In November, MDF staff met with the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) and the National Institute of Neurological Disorders and Stroke (NINDS) senior leadership and program/policy staff to discuss research opportunities and federal support for myotonic dystrophy (DM). Discussions focused on two areas: the scientific workforce and biomarker and registration endpoint development.

MDF reviewed efforts to support the scientific workforce through the MDF Postdoctoral Research Fellowship program and expressed support for NIAMS and NINDS efforts to extend their R01 paylines for new investigators. Dr. Steve Katz, Director, NIAMS, noted that 58% of K award recipients successfully transition to R type awards and encouraged clinical researchers in DM to utilize the K award mechanism. Dr. Walter Koroshetz, Director, NINDS, noted that 22 academic medical centers currently held NINDS R25 awards to support resident’s research in neurology; he encouraged faculty working on DM at these medical centers to take full advantage of the R25 awards.

MDF also encouraged NIAMS and NINDS to consider mechanisms to support young faculty seeking to renew their initial R01 awards. This is often a critical stage for young investigators (and NIH data bear that out), as they have had to set up their lab, produce on proposed projects, and gather preliminary data for specific aims of the renewal within the initial five or fewer years of funding. The NIAMS and NINDS directors indicated that they were sensitive to the issue. Dr. Katz noted the NIAMS STAR Program (Supplements to Advance Research from Projects to Programs). This program provides up to $150,000 per award in administrative supplements to young faculty on their initial R01 who need additional time and data to obtain either a renewal or a new R01 award. Young faculty with an initial R01 from NIAMS should review the program announcement.

MDF staff also reviewed the Foundation’s role in addressing opportunities and challenges along the entire therapeutic development pipeline. The potential for development and qualification of biomarkers for use in early phase clinical development was highlighted as a timely opportunity in DM. Likewise, overcoming the challenges in developing registration endpoints for drugs and biologics under development for DM were identified as a critical need.

NIAMS Staff pointed to RFA-AR-17-009, Research Innovations for Scientific Knowledge (RISK) for Musculoskeletal Diseases (R61/R33), a program designed for high-risk projects, as a potential means of funding biomarkers and clinical endpoints in DM. NINDS has a continuing program targeted at clinical trial readiness (including biomarker and endpoint development): PAR-16-020, Clinical Trial Readiness for Rare Neurological and Neuromuscular Diseases (U01).

Since the NIAMS initiative has only one application date, and the NINDS initiative is intended for mature projects, such as biomarker qualification efforts, MDF staff strongly encouraged both institutes to consider an initiative to facilitate early discovery and development of biomarkers and endpoint measures for DM. MDF believes the existing funding opportunities are important, and should be considered by investigators, but noted that early stage discovery projects in these areas may not compete well with hypothesis-driven applications and that a targeted initiative is a critical need for the DM field.

Taken together, MDF will remain engaged with the NIH, meeting on a regular basis to ensure that opportunities and critical needs in the DM field receive attention. DM researchers are encouraged to make opportunities and needs known to MDF staff so they can be incorporated into discussions with NIH leadership and program staff.

The MDF community is an amazing network of volunteers and advocates who inspire us all with the work they do to advance Care and a Cure for DM. Each year at the MDF Annual Conference we honor those who are doing outstanding work with Community Leadership Awards.

Congratulations and an enormous “Thank you!” to this year’s winners!

Advocacy Champion Award Winner

Carolyn Valek: community member with the most outstanding contribution to promoting awareness of DM this year

Carolyn Valek is one of MDF’s original Phone Buddies. She uses her experience as a patient advocate to dispense critical information to those in need. Her warm personality and deep concern for the community help newcomers quickly feel at home.

Carolyn runs the MDF Ohio support group and is an integral part of our newly launched Virtual Caregivers Support Group. She is one of our most devoted advocates, calling representatives on Rare Disease Day, writing letters to Congress to support the Orphan Drug Act, and attending MDF Hill Days in Washington, DC.

Congratulations and thank you Carolyn!

Team MDF Volunteer Award Winner

Loraine Dressler: community member with the most outstanding contribution to ensuring that the people in the best position to help have the knowledge they need to make a difference

Loraine Dressler’s dedication to supporting the DM community and her glowing positivity make her an inspiration to others. Loraine runs MDF’s Orange County support group and will also be participating in MDF’s Virtual Caregivers Support Group.

She takes part in our Grandparents’ Day awareness and fundraising campaign and is a long-time advocate who has met with members of Congress to advocate for DM funding and has provided testimony on the impact DM has had on her family to the Social Security Administration.

Congratulations Loraine! You are wonderful!

Humanitarian Award Winners

Taylor and Eric Jensen: community members with the most outstanding contribution to amassing resources for Care and a Cure

Taylor and Eric Jensen are a formidable grassroots fundraising team. They have turned their annual friends and family crawfish boil into a much anticipated and highly successful community celebration to support Care and a Cure. “Pinching Tails for a Cure,” has raised more than $110,000 since it began in 2013.

The Jensens also do all they can to help raise visibility for DM. They share their family’s story with reporters, participate in MDF awareness campaigns and speak at key events like the Ionis Pharmaceuticals Rare Disease Day employee event to help educate the world about DM.

Congratulations Taylor and Eric! We truly appreciate all you do!

"We will not forget your faces or your stories. Please know that all of your efforts will make a contribution to making [the regulatory review] process go smoother when a new treatment comes to the FDA to be reviewed."

- Dr. Larry Bauer, regulatory scientist, FDA

Optimizing the Review & Approval Process for DM Therapies

As many of our community members know, MDF held the first myotonic dystrophy (DM) Patient-Focused Drug Development (PFDD) meeting with key senior leaders from the Food and Drug Administration (FDA) as part of the 2016 MDF Annual Conference. We designed the meeting to build on the work MDF has been conducting with the FDA to define and optimize the regulatory pathway for potential DM therapies.

The DM PFDD Meeting – Why Do It?

The DM PFDD meeting, which was the first Externally-Led PFDD Meeting sanctioned by the FDA as well as the first PFDD meeting focused on DM, was conceived to follow on these earlier meetings, and particularly the full-day workshop in 2015, by moving from reports and discussion from regulators, academic researchers and industry professionals to insights and information provided directly by people living with DM and their caregivers. Decision-makers are increasingly realizing that the voice of the patient is a critical element in understanding how to develop and approve therapies that provide clinically-meaningful benefit to those living with a particular disease. Without patient insights, the FDA’s ability to assess the benefits and risks of a particular therapy, and its ability to provide real benefit to patients, is significantly impaired.

Laying the Groundwork – Earlier DM FDA Meetings

Earlier MDF meetings in 2014 and 2015 focused on the status of biomarker and endpoint development, insights and challenges with regard to DM clinical trial design and other key regulatory questions. The full day regulatory workshop MDF hosted in September 2015 included presentations from leading DM clinicians and researchers, and FDA representatives in divisions and offices that impact the regulatory pathway of DM therapies, including the Study Endpoints Team, the Office of New Drugs, the Office of Drug Evaluation 1 - Division of Neurology Products, which will be in charge of the actual review of potential DM therapies, and a number of other functions in the Center for Drug Evaluation and Research (CDER) at FDA.

The Largest PFDD Meeting Ever

Well over 200 community members, industry professionals, academic researchers and FDA representatives attended the meeting live and via the live stream MDF provided. FDA leadership including Dr. Janet Woodcock, who oversees all drug evaluation and research at FDA as the Director of CDER; Dr. William Dunn, who is the Director of the Office of Drug Evaluation 1 – Division of Neurology Products, the division that will review all DM therapies; Dr. Jonathan Goldsmith, Associate Director of the Rare Diseases Program, Office of New Drugs, CDER/FDA; Dr. Larry Bauer, a regulatory scientist in the Rare Diseases Program; and a number of additional representatives from the Office of Health and Constituent Affairs, the Office of Translational Sciences, the Study Endpoints team, and others also attended.

DM PFDD Meeting – Engaging the Audience

MDF held the DM PFDD meeting on Thursday, September 15, 2016 from 1-5 PM ET in a conference hotel located near the FDA campus. James Valentine, a former FDA professional who helped launch the PFDD process at FDA and who now works in private practice advising industry and others in the therapy development arena, facilitated. The meeting began with a review of disease manifestations and a clinical overview from Dr. Charles Thornton of the University of Rochester. We then moved to audience polling to understand the demographics of those attending the meeting, either live in the conference room or via live stream.

Attendees provided information on their diagnosis (DM1, DM2, CDM), whether they were a patient or caregiver, when they were diagnosed, first experienced DM symptoms, their age range, etc. MDF has no information on who the specific attendees were and how they voted; however the demographic information allows us to tie specific polling responses to the demographic particulars of participants - for instance patients versus caregivers, DM1 versus DM2 respondents and much more. Only patients and caregivers were allowed to vote during the polling sessions; academic, industry and federal agency attendees were not.

All polling results displayed immediately on the screen at the close of polling for each question, so that attendees in the room and participating remotely could see how the full audience was voting, and how their answers and experiences aligned with others.

Living with DM – What the FDA Wants to Know

The first panel presentation, entitled Living with DM, took attendees to the heart of the meeting agenda. This session began with remarks from four panelists selected by MDF to represent key elements of the DM community, including patients with DM1 and DM2, caregivers, individuals with congenital or childhood-onset DM, etc.

The Living with DM panel questions were:

• What 1-3 symptoms of DM have the most significant impact on your life?
• How do they affect your life on a typical day? On your worst day?
• Are there specific activities that are important to you that you can no longer do or do as well because of your condition?
• How have your symptoms changes over time?

MDF panelists for panel one included Glen Wiggans, Athens, GA; Judy Marks, Raleigh, NC; Lee Baker, Roanoke, VA; and Sarah Clarke, New York, NY. Each panelist gave five minutes of prepared remarks responding directly to the questions posed to the Living with DM panel, providing personal stories and examples that painted compelling and vivid pictures of life with DM1, DM2 and the experience of caregiving for family members who live with the disease. Their stories were factual, detailed, moving and sometimes funny, and added immeasurably to the perspective and understanding of those in the room who were there to learn.

Panel One Audience Input

Attendees in the room and participating via live stream also responded to the panel one questions via live and remote polling, and via moderated audience discussion. The audience polling and moderated discussion provided additional voices and perspectives to the FDA and enabled the facilitator to probe more deeply around topics highlighted as particularly significant by the polling responses.

Dr. Janet Woodcock, MD, the head of research and drug evaluation at FDA and a strong proponent of including the patient voice in drug development and evaluation, addressed attendees, congratulating MDF on hosting the first Externally-Led PFDD meeting and outlining additional opportunities for productive patient advocacy engagement in the regulatory environment.

More Community Insights – Challenges of DM, a Short Film

A picture (or short film) is often worth a thousand words, so MDF screened Challenges of DM, a short film we created specifically for the FDA as an educational tool. The film included short interviews with DM community members around the country who do not attend MDF events, and featured voices and experiences we felt were critical to creating a holistic picture of the DM disease experience.

Panel Two – Current and Future Treatments

Four new panelists presented on strategies and interventions currently used in their families to manage disease symptoms, how effective or ineffective these are, drawbacks and side effects, and what they would most like to see from future therapies.

Panel Two questions included:

• What current treatments or therapies do you use for symptom management?
• How well are these therapies or treatments working?
• What are the downsides, if any, to these treatments or therapies?
• What do you want from an ideal treatment?

Panelists included Pat Dinsmore, WA, DC; Suzette Ison, Morristown, IN; Joachim Boekelmann, Princeton, NJ; and Tom McPeek, Chillicothe, OH. Their presentations highlighted the significant lack of effective treatments and interventions available to people living with DM and the importance of finding and approving effective therapies soon. Audience members responded to the panel two questions during the polling session and moderated discussion, rounding out DM community perspectives regarding disease management strategies and community hopes regarding eventual therapies.

FDA Feedback – Well Done

Dr. Jonathan Goldsmith, MD, who is Associate Director of the Rare Diseases Program in the Office of New Drugs, CDER, FDA, wrapped up the meeting by reflecting on what he, as an FDA participant and listener, had heard from the panelists and attendees. He touched on the very real need that exists for effective therapies, and the profound and ongoing struggles families with DM live with every day. Dr. Goldsmith demonstrated, through his summary remarks, that DM is understood to be a real and specific disease for FDA attendees, and not just "muscular dystrophy".

Perhaps equally compelling, MDF received an email from Dr. Larry Bauer the next day, in which he congratulated MDF on the quality and scope of the DM PFDD meeting, stating:

"Please know that all of the FDA attendees were enlightened, deeply moved and educated about the realities of living with myotonic dystrophy. We will not forget your faces or your stories. The meeting also made it extremely clear how much a treatment is needed for DM. Please know that all of your efforts will make a contribution to making that process go smoother when a new treatment comes to the FDA to be reviewed."

Our Thanks to You

We at MDF would like to thank all our community members who made time to attend the meeting, either in person or via live stream, and participate in the polling that created specific feedback for the FDA. We are incredibly grateful to the panelists who spent significant time writing and editing their remarks, participating in practice sessions and helping represent the DM community to the FDA.

There Is Still Time to Share Your Thoughts

MDF is currently assessing the polling results and analyzing the responses received against the demographic information provided, to understand better how, for instance, DM1 versus DM2 patients responded to key questions, how caregiver input differed from patient input, any interesting regional differences, etc. We will create a Voice of the Patient Report this fall, which we will deliver to the FDA for use in future drug review processes. The Voice of the Patient Report will be critical content the Neurology Review division will take into account when assessing the benefits and risks of specific drugs, and whether they will provide therapeutic benefits that are meaningful to patients.If you were unable to participate via live stream or in the meeting on September 15th, you can still provide answers to the questions posed to panels one and two. MDF will accept emailed or telephone responses to the questions until 5 PM PT Saturday, October 15th, 30 days after the DM PFDD meeting.

Questions?

Contact MDF via email or at 415-800-7777.