Matt’s Promise is dedicated to making a difference
in the lives of young people affected by terminal illnesses.
Our cornerstone project is to find a cure for Duchenne Muscular Dystrophy (DMD).

Matt’s Promise is dedicated to making a difference in the lives of young people affected by terminal illnesses.
Our cornerstone project is to find a cure for Duchenne Muscular Dystrophy (DMD).

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The Impact Initiative: Actions to Increase our Odds

The Impact InitiativeOverview

Since 2005 our sister organization Charley’s Fund — with crucial support from DMD community organizations — has directed more than $35MM to medical research and drug development with the intention of developing treatments for Duchenne. Today, 10 years in, there are still no FDA approved treatments to improve and lengthen our children’s lives. The clock is ticking ever louder for all boys with this dread disease. We have to work smarter and better to get safe and effective drugs developed and approved for use by all kids with Duchenne.

The array of scientific projects they have funded are varied — from assays to high throughput screening to animal model studies to human clinical trials. Our support has resulted in significant interim achievements: They now have a more sensitive assay that can screen drugs against known therapeutic targets. They have concluded two clinical trials using drugs that are FDA-approved for other medical conditions. Two molecules have new formulations, a crucial step that redirected them from scrap pile to promising clinical path. A clinical trial is underway at five sites in the US to test the first drug that could treat all kids with Duchenne, regardless of genetic mutation. These are important advances, but they are intermediate steps toward our ultimate goal: safe and effective treatments that are approved for use by all who can benefit. So why aren’t we there yet?

Prompted by the milestone of our 10th year, they took a look at the “shots on goal” that have been taken, or — to drop the metaphor — the list of drug development and medical research projects they have supported with the intention that they would translate into treatments for the boys. They identified 15 potential “wins” that could have resulted from their work. For fourteen of the projects, a “win” is defined as regulatory approval of a new treatment. For the fifteenth, it is FDA validation of an objective, highly sensitive outcome measure for clinical trials that can be used at any stage of disease progression. To date, not one of those 15 potential wins has crossed the finish line. Why?

Perhaps surprisingly, only three of the 15 projects hit a dead end because the science did not merit pushing ahead. Two of the 15 are moving along well, but it is too early to consider either of them a win. That leaves ten out of 15 initiatives not moving forward efficiently for reasons other than the quality of the science.

It became clear that in addition to funding the best “shots on goal,” they must also invest resources — both financial and human — in solving the problems that make it so hard for those shots to sink into the net. This concept itself is not a new one: problem solving and roadblock removal are part of Charley’s Fund’s DNA. Some examples: To move HT-100 from discarded molecule on a shelf to promising clinical candidate, they had to acquire the drug, reformulate it, and build a team to take it to the clinic. When a talented academic team discovered that a peptide found in spider venom could potentially regulate calcium influx but didn’t know how to translate this finding into a drug development plan, they helped craft and implement a development program and have now identified the appropriate dose level for use in human trials. Facing FDA confusion about how to interpret exon-skipping data, they educated the Agency, informed Congress, and rallied the public to demand timely and clear communications from the FDA to the drug companies.

What is new is the scale on which they must now apply this strategic problem-solving approach. We cannot wait for problems to present themselves and then solve them one at a time. We must apply lessons learned over the past ten years and be proactive in heading future problems off at the pass. We need fast, effective clinical trials that value our boys’ time and muscle, and we need a clear path to regulatory approval. But paving this path for impact requires work, and to increase our odds we need to act now by thoughtfully and strategically laying the right groundwork.

While elements of this effort have been underway for some time, this year — in an effort to amplify their impact — we are codifying this effort into a program with a name, key deliverables, and realistic look at the resources required. The Impact Initiative will identify and then solve systemic problems that make drug development slower, more difficult, and more costly. Importantly, this Initiative seeks to increase the odds of success for the entire field of medical research and drug development programs that various foundations, both on their own and through the Duchenne Dashboard, are supporting.

Execution

The Initiative will have three phases (the three D’s):Discovery, Definition, and Delivery. Structured in this phased approach, they aim to keep our “eyes on the prize” and ensure any action undertaken has a clear rationale and represents the shortest, best way to accelerate research.

Each phase has a clear objective and aims to inform the strategy and shape of the next phase. The findings researched, analyzed, and synthesized in Discovery (phase 1) will inform the plans shaped in Definition (phase 2) and executed in Delivery (phase 3).

Phase 1: Discovery

Objective: Research and understand the institutional and structural roadblocks that keep promising therapies from advancing through the drug development pipeline swiftly and efficiently; identify solutions.

Timing: 2Q 2015; progress underway, mid-point check-in planned for May

Phase 2: Definition

Objective: Define and refine courses of action needed with associated budget and timeline

Timing: 3Q 2015; to be refined ongoing as Discovery proceeds

Phase 3: Delivery

Objective: Implement the program(s) identified and defined in the first two phases and deliver results

Timing: 4Q 2015, to be confirmed as Discovery and Definition proceed

This first phase, Discovery, is already underway. Building on the objectives and timing defined at the start of the project, a more detailed framework governing this phase includes the following key questions, activities, and resources. As Discovery proceeds, a similar framework will be established to inform the Definition and subsequently Delivery phases.

Phase 1: Discovery

Objective
  • Research and understand the institutional and structural roadblocks that keep promising therapies from advancing through the drug development pipeline swiftly and efficiently, and identify potential solutions
Key Questions
  • Where do our current outcome measures and approaches to advancing drug development fall short? Is it scientific precision? Practical challenges? Lack of regulatory understanding? Or something new? What are “low-hanging fruit” opportunities to solve these shortcomings, and where is it simply necessary to identify/develop something better?
  • Where do new tools — including EIM, MRI, emerging biomarkers — offer promise in both scientific/regulatory merit and meaningfulness to the patient community (e.g., avoiding biopsies)?
  • How do we prioritize, and what does a roadmap for results look like? What suite of actions offers the shortest, best route to advance treatments to boys with Duchenne, and what resources are required to enable success?
Key Activities
  • Survey DMD key opinion leaders in academic and industry world for input on gaps, strengths, weaknesses, and opportunities
  • Conduct secondary research on use of relevant outcome measures in other indications, relevant regulatory standards, case studies and guidance for clinical outcome measures in DMD; identify examples to learn from and short cuts to apply
  • Identify external drug development regulatory expertise resource and collaborate to further shape strategy and approach
  • Synthesize research and external inputs into proposed roadmap for next steps

 

 

Convergence Medical DevicesConvergence Medical Devices

As promising treatments enter the clinical development stage, it is increasingly clear that better outcome measures are needed to help determine the efficacy of an experimental medication. Currently, the most common outcome measure is the six minute walk test, which has notable drawbacks. For example, that test can only be used in ambulatory patients, which significantly limits the pool of patients available for clinical trials.  One potentially powerful solution is being developed by a company called Convergence Medical Devices.  CMD was formed to optimize and develop an incredible technological advancement discovered by Dr. Seward Rutkove, Director of Neurology at Beth Israel/Deaconess Hospital in Boston. Based on electrical impedance myography (EIM), the company is developing a portable, hand-held, non-invasive device that a physician or researcher could place over a muscle and get measurements that correlate with the health of the muscle. With our help, Charley’s Fund is financing an initiative to explore the use of this technology as an outcome measure in clinical trials.

For more information please visit Skulpt Health