‘Even against the greatest of odds, there is something in the human spirit, a magic blend of skill and faith and valour, that can lift men from certain defeat to incredible victory’ (Walter Lord Author)

Children and young adults living with Duchenne face certain defeat from a condition that will take their lives each and every time. But this week I was lucky enough to be reminded of the skill and faith and valour of a community of Duchenne patients, families, clinicians and scientists who are dedicated to lift the curtain of certain defeat by slowing or stopping Duchenne in its tracks.

Monday’s Advisory Committee meeting with the FDA was a difficult day for the Duchenne community as they listened to what is the predictable outcome of Duchenne then heard how a group of boys who had been receiving Eteplirsen for a period of 4 years had not only stopped getting worse but had in fact started to regain skills that they had lost: Aidan Leffler went from falling 2-3 times a day to not falling at all; Dr Anne Connolly a neurologist at Washington University said she would have classified her patient with the milder Becker Muscular Dystrophy had she not known him and the progress of his condition prior to his enrolment on Eteplirsen; we saw video diaries of boys gaining the ability to climb into their parents car unaided, we watched video footage of a non-ambulant, 16 year old Austin Le Clair lift his arm over his head, reach into  a backpack on the back of his chair and transfer himself to bed – skills he had lost some years ago.

We heard Duchenne experts – clinicians and scientists –  describe their findings: We heard Dr Elizabeth McNally (Director at the Centre for Genetic Medicine, Northwestern University) describe a ‘clear difference between treated and non treated’ and how ‘any increase in Dystrophin is beneficial’. Dr Lou Kunkel, Professor of genetics and paediatrics at Harvard medical school, said of the Dystrophin produced ‘0.9% is a remarkable amount, there is no reason not to approve’. We heard Dr Perry Shrieh, MD PhD Neurophysiology, Neurology and Neuro muscular Medicine, stress that the data is positive and he sees no reason not to approve.

But such positive outcomes from patients and expert advice was blatantly ignored by the FDA who provided misleading arguments for the non-approval of Eteplirsen. Eric Bastings, MD Deputy Director Division of Neurology and Drug Products with the FDA said ‘We are a science based organisation’ but yet they fail to take the advice of experts in the field. His colleague Ronald Farkas argued that ‘kids could walk if they put their minds to it’. Such utterances only serve to iterate that the FDA is not an expert on Duchenne – if only maintaining the ability to walk were a choice. If only he could see how hard the boys try to stay walking, if only he could understand the impact that losing that ability had on a life, perhaps then he would base his arguments on science and not simply on mere speculation that the boys in the trial perform better because they are ‘more motivated’ (his words not mine).

The outcome of Mondays meeting was a crushing defeat for the entire Duchenne community. For me it was like diagnosis day all over again as I was forced to accept that the reality that in all likelihood I will bury my son. Rigid practices by regulatory authorities and an unwillingness to hear expert testimony and personal experiences will continue to make it impossible for any rare disease drug to make it to market. Throughout our Duchenne journey I have always tried my hardest to ensure that hope takes precedence over my fear of what Duchenne will do to my son and to stay positive but I will admit that on Monday evening, my hope shattered and no matter how hard I try I cannot find the words to describe that feeling.

But losing hope isn’t an option and so I will resign myself to the fact that the fight for Eteplirsen is not over yet. The FDA will make their final decision on May 26^th and in that time we appeal to Janet Woodcock of the FDA, and ultimately the key decision maker, to urge her team not to make what she calls a type 2 error and describes as perhaps the most dangerous error the FDA can make i.e. failing to approve a drug that works. Janet herself questioned the integrity of the voting questions put to the panel, which ultimately led to a no vote. Ms Woodcock, we urge you to recognise the testimony of Duchenne experts with decades of experience in the natural history of the progression of the condition and listen to the patient voice. The Duchenne community is not a group of desperate parents who will try anything, we want safe and effective treatments for our children. We want treatments endorsed by experts and that will change the course of the disease and will improve our children’s quality of life beyond measure. Eteplirsen does just that. It has a perfect safety record, experts attest to it’s efficacy and the boys on the trial are living proof that the drug works. Our scientists have the skill, our doctors have the faith and our boys have the valour to lift our community from certain defeat by Duchenne. You have the power to help us and the potential to save a generation. Please do the right thing.

This morning I kissed my 2 sleeping little boys as I crept around the house before the crack of dawn getting ready to leave them for 4 days, longer than I have ever left them before. And I have to admit my heart is a little anxious. But my reason for leaving is necessary. Because for the first time since Duchenne entered our family over 60 years ago, we have an opportunity to be a part of history, a part of a movement that will push through a treatment with the potential to help slow the progression of Duchenne in around 80% of patients (Eteplirsen will help 13% but follow on drugs will help up to 80%), to show that the patient voice matters and to let regulators see that following archaic practices of drug development for rare diseases simply does not work and is in fact immoral, unethical and unjust. Especially given that the drug in question has an impeccable safety record and has been endorsed by 36 Duchenne experts, clinicians who have seen thousands of Duchenne patients, to have shown significant efficacy in slowing the progression of Duchenne in all the boys who have been receiving the drug in trial for the last 4 years.

Around two thirds of Duchenne cases are caused by a deletion of one or more pieces of the Dystrophin gene, meaning that children with Duchenne cannot produce an essential protein, Dystrophin, which is vital for muscle repair. Without Dystrophin, every muscle in the body simply wastes away, leaving patients like Luke paralysed and at severe risk of heart and lung failure. Eteplirsen is the first in a pipeline of drugs designed to ‘patch over’ the missing piece, allowing the body to produce a small amount of Dystrophin, but a tiny bit of Dystrophin is all that is needed to slow muscle damage and to add years to the walking ability of children with Duchenne. Which in turn adds years to their life expectancy.

Eteplirsen won’t help Luke and even if campaigners are successful in getting it approved by the FDA, it will only be available in the U.S.A. so why is it so important to us that it is approved?

The technical answer – Approval of Eteplirsen by the FDA will be a monumental step forward for the entire Duchenne, and in fact, wider rare disease communities for many reasons. Firstly, Eteplirsen is simply the first in a pipeline of drugs being made by Sarepta Therapeutics that use exon skipping technology to treat the underlying defect causing Duchenne. Together this pipeline has the potential to provide part of a cocktail of treatments for around 80% of Duchenne patients. If Eteplirsesn is not approved by the FDA, it will put paid to the hopes of hundreds of thousands of families who will witness the failure of the most advanced potential treatment for Duchenne, a 100% fatal condition for which there are no treatments. This failure will be made all the more heart breaking, given that the treatments works – it meets its primary objective of slowing the progression of Duchenne.

Secondly, the failure of Duchenne experts and families to convince the FDA of the efficacy of Eteplirsen will deter the bio tech industry from investing in research for Duchenne and many other rare diseases. After all, while the trial population was small, the drug has a perfect safety record and of the 12 boys who started out on the trial over 4 years ago (chosen specifically because their condition was deteriorating rapidly and they were likely to come off their feet imminently), 10 are still walking compared to a comparable group of Duchenne boys not receiving the drug and where only 1 out of 11 is still walking. If a drug like this can’t be approved then why should drugs companies spend millions developing drugs that work but that will never see the light of day?

Thirdly, the FDA have a moral duty to put patients before process. The FDA continue to use drug development processes implemented decades ago. These processes do not allow for innovation in medicines and certainly don’t create a platform for the approval of new innovative, personalised medicines, the only medicines likely to pave the way forward for hundreds of lethal rare diseases. By not granting Accelerated Approval for Eteplirsen, the FDA will be showing the world that they want to continue to live in the dark ages and their decision has the potential to deter a generation of innovative and life saving medical research.

The Duchenne population is limited, and these limitations are even more restricted given the personalised nature of exon skipping technology, so traditional trials consisting of hundreds of patients half of whom are on placebo is simply not an option. Who in their right mind would put their child through years of clinical trial procedures and painful risky muscle biopsies if there was a chance that all they were getting was water? Duchenne is a muscle wasting condition remember, these kids have little enough muscles as it is.

Fourthly, the approval of Eteplirsen will create a clear, transparent and usable way forward for future personalised medicines and will lead to an accelerated pathway for follow on exons, putting life saving drugs in the hands of children before it’s too late. Especially considering that there are no drugs in development designed to reverse the effects of Duchenne. Time is life in this situation.

Even though FDA approval will only make the drug available in the U.S.A, it’s approval there may make it more likely to be approved in Europe by the European Medicines Agency (EMA).  Approval will allow patients to work with Sarepta Therapeutics and the EMA to ensure that approval is granted as soon as possible and will bolster the argument of patients, advocates and families that the EMA should use accelerated pathways to approval, not just for Eteplirsen but for follow on drugs as well.

My ‘real life’ answer  – As I fly off today, I am filled with apprehension, nerves and excitement. Apprehension because I am all too aware that we may not be successful. Nervous because travelling alone to engage with a huge group of people is so far outside my comfort zone, and excitement because I can feel the enormity of the situation and I have an opportunity to be a part of history at the largest Advisory Committee meeting the FDA has ever seen.

Duchenne has broken dozens of hearts in my family, it has taken 4 boys from us including my only brother, and threatens the life of my son and my cousin. It has caused countless tears and sleepless nights, it has taken over my life and on a positive note it has perhaps moulded me into the person I am today. Someone who has had enough, someone who simply can’t sit back and take it anymore. It has given me my fight. But I wouldn’t have that fight if it weren’t for the promise of a treatment.

Eteplirsen simply has to be approved. Exon skipping technology has the potential to save Luke’s life. We are lucky in that the exon he needs skipped is next in the pipeline with trials having already started in the U.S.A. Eteplirsen’s approval will, in all likelihood mean Luke could have a treatment before he loses his ability to walk. The promise of exon skipping has been a life line to me since Luke’s diagnosis. It has been the one thing that has kept my hope alive and it is that hope that has given me the drive and passion to carry on knowing what the future holds for Luke. I spend countless hours researching, fundraising, campaigning, building awareness, all because I want to tell Luke that I tried. I want to teach him to never give up, to persevere, to push for what he wants in life but if Eteplirsen, and indeed the whole exon skipping technology, the most advanced potential treatment for Luke and that is still some years away, is refused approval, then I wonder where the hope will come from. I have no doubt that I will see a viable treatment for Duchenne in my life time but failure of Eteplirsen could mean that it will not come in Luke’s life time and that is a bite that is just too hard to swallow.

So to the FDA, I say look at the facts, the drug is safe and effective and 4 years of data and the real life experience of the children on the trial for 4 years prove that. The potential to save or indeed extend the lives of thousands of children is in your hands, don’t let your need to stick to rigid and archaic processes trump the lives of children. Don’t say that a generation of research has been wasted when this drug works. Don’t shatter the hopes of families with children with rare disease all over the world because you feel you can’t back down. See the real picture, listen to patients and families and do the right thing.

‘I’ll love you forever, I’ll like you for always, as long as I’m living, my baby you’ll be’ (Robert Munsch)

This is one of my favourite books to read to my boys, and it was the one Luke chose to read last night and the timing could not be more relevant.

Tomorrow, that crazy little boy I’ll love forever and Like for always, the one that made all my dreams come true when he made me a mum, will celebrate his birthday. I just can’t quite believe that it’s been 5 years since I first cradled that little 9lb 1oz bundle of love in my arms. Since my heart completely and totally belonged to the little boy who would grow to call me his mummy.

I think for most mums, birthdays bring a melting pot of emotions, they are happy and proud of their growing children but realise that childhood is short, and soon, their little ones will be all grown up. But when your child is life limited, birthdays become so much more significant and seem to come around much too quickly with each passing year.  Luke has had 5 years of muscles wasting, 5 years waiting for a treatment. He’s more than half way to the age that most boys with Duchenne become wholly dependent on wheelchairs, he’s 5 years closer to needing 24 hour ventilation just to keep him alive, 5 years closer to not being able to lift his arms to hug me, and 5 years closer to the inevitable end that Duchenne always brings.

But he is just like any other little 5 year old excitedly waiting for his big day. In his pure and perfect innocence Luke, my little sugar monkey, says all he wants for his birthday is icing (yip the cake topping lol). But my birthday gift to him will be much more than icing or the super cool go kart that he has recently learned to pedal. My birthday gift is a promise – a promise to always love him; a promise that his happiness will always be more important than my sadness over how Duchenne will impact on his life; a promise to renew my resolve to do whatever is in my power to make him proud, to keep him on his feet, to make sure he has the best chance at life. To keep his lungs breathing and his heart beating. And above all, a promise to give him as normal a life as possible. I promise to tell him off when he’s naughty and teach him right from wrong. I promise to teach him the value of life’s most important things – friends, family, love and hope and I promise to try my best to give him the independence all kids need when growing up and to teach him that dreams are worth fighting for – even the dreams that seem almost impossible.

While the last 5 years have moved Luke closer to the inevitable consequences of Duchenne, they have also been filled with wonderful happy memories. I’ve had 5 years of cuddles, and giggles, and little boy chats. 5 years of tripping over Thomas the Tank Engine trains and toy dinosaurs and I’ve watched the movie ‘Cars’ more times that I would want to count and I’ve loved every second of it.

So to my baby boy on your birthday, I promise to love you forever and like you for always. I will do whatever it takes to make you happy and to give you many many many more happy birthdays.