Parliamentary Duchenne Rare Exon Meeting Report 26th March 2013
In Spring of this year, PPMD and other Duchenne stakeholders from around the world, convened a meeting with the UK's Shadow Minister of Health, Andrew Burnham, at Parliament. The purpose was focused on Antisense oligonucleotides (exon skipping) and developing an expedited pathway for all children with ‘fixable’ mutations. The meeting included particular reference to "rare exons." Click here for the report produced outlining the discussion and next steps.
On March 26, PPMD President Pat Furlong, along with other members of the Duchenne community (internationally, including those like Pat that traveled from the U.S.) met with the UK's Shadow Minister of Health, Andrew Burnham in a meeting at Parliament.
Setting the Stage
The meeting opened with a video, that of a 4-year-old boy, Jack, diagnosed in October 2011. His parents Alex and Andrew Johnson rolled up their sleeves and started the Joining Jack Foundation, focused on accelerating treatments for Jack and for all people with Duchenne. Today’s meeting happened because of their advocacy, telling their story, and connecting with the Shadow Minister of Health in the UK Parliament.
The video shows Jack in the pool – smiling, laughing, playing and the ask, “JOIN JACK” to help, to hope, to end Duchenne. As the video played, his mom stared at the computer watching her small son and hoping with all her heart, that Jack would never stop walking, never stop playing, never stop…
Shadow Minister of Health
Champions in Government
Andy Burnham started the meeting by saying that this particular meeting was focused on Antisense oligonucleotides (exon skipping) and developing an expedited pathway for all children with ‘fixable’ mutations.
“Is there a collective will to move forward?”
Everyone in the room – the patient community, EMA/FDA representatives, clinicians, industry, government nodded in agreement.
Thomas Voit, MD suggested acceleration required novel designs for clinical trials with small numbers of patients, assurance of safety, endpoints based on defined timelines, an understanding around what constitutes a meaningful change, and an improvement in quality of life. He believes patients/families should have a very strong voice.
Emily Crossley (Duchenne Children’s Trust) asked about a pathway for industry to work together on rare exons – to ‘divide and conquer,’ that making decisions about specific chemistries for rare mutations be agreed upon by interested companies, with patients/foundations supporting development.
Representatives from EMA and FDA suggested that companies have approached the agencies in this way – to work together to develop compounds for rare diseases. Companies are able to request EMA and FDA act in parallel, reminding us that meetings should be early and often and that data drives decision. Though, they suggested it is too early to make definitive decisions, they first have to understand/have assurance of safety and understand margin of benefit.
Industry expressed concern about timelines for interaction and review and asked about ways to expedite meetings. EMA and FDA representatives suggested that the 75-day waiting period allows time for both agencies to meet so that they are able to align and reach harmonization with regard to the development program.
Prosensa has six compounds in development; Sarepta has four. Both companies suggested they have plans to treat all mutations amenable to the exon skipping strategy. They are hopeful that once the first compound is approved (anticipated to be exon 51 skip), regulatory agencies will allow them to extrapolate the data, expediting development of exons currently in the pipeline and others in their development plan.
The devil is always in the details – how to extrapolate to other exons, what is the degree of benefit required, what is the acceptable regulatory pathway (how much tox /animal data will be required), and what is the acceptable path for patients with no time to wait.
The plan will require regulatory flexibility and TIME – of which the patients have little of. TIME will depend on the burden of proof required. And the patients/families need to raise their voice, speak ‘early and often’ with regulatory agencies, and talk about risk tolerance (what they are willing to risk and what benefit they will accept), recognizing that these early compounds are a first step and that stabilization of disease IS benefit in a progressive, debilitating disease.
Regulatory agencies need to address what is negotiable and what is not as it would be useful and critical to have regulatory consensus about what is required for follow-on exons.
In the words of Thomas Voit: “The field needs to move forward in a plan-able way to optimize and rollout compounds for all who are likely to benefit.”
The Patients are waiting….
Pat Furlong, Founding President, CEO
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