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by Molly White, Dyne Therapeutics
It has been a banner year for the biopharma industry, with record investment, groundbreaking COVID vaccine efforts and incredible scientific advances. It is a particularly hopeful time, both for the industry and for the people living with diseases that our companies are addressing. At the end of the day, though, it only matters if the resulting therapies drive real improvement in the quality of life of affected community members. To be truly transformative, drug developers must understand the burden a disease presents, what meaningful change looks like to the people living with it and how to design the resulting therapy with that information top-of-mind. That information is equally important to the regulatory agencies that seek to sensitively and effectively make drug assessment decisions based on what patients say matters most.
Achieving this requires dogged and continuous consideration of the end user, and the FDA’s Patient-focused Drug Development initiative is a powerful tool to facilitate this focus.
The newly-released FSHD Voice of the Patient Report is a case in point. The FSHD Society organized the externally-led PFDD meeting, partnering with other advocacy organizations to extend its reach and engagement. The report is now listed on the FDA website.
Capturing how profoundly FSHD changes people's lives
A pre-meeting survey gathered almost 600 responses to help hone and target the content and discussion. Despite the impact of COVID-19 and the necessity for a virtual meeting, the event went swimmingly, with illuminating panel presentations, inclusive conversation, and real-time polling feedback that demonstrated how diverse and geographically diverse the audience was.
More importantly, the report captures in compelling, visceral detail what living with facioscapulohumeral muscular dystrophy is like, and how profoundly it changes peoples’ lives:
- The impact of facial weakness on speech: “Each word I use must be weighed. Will it be difficult to pronounce? Is there another word that would convey the same emotion in a meeting that might be easier for me to use?”
- How quickly and profoundly the disease can progress: “Twenty-two was the last time I used a regular [bathroom stall] because I couldn’t stand without grab bars. [Age] 23 was the last time I drove because, I couldn’t pick my foot up off the pedals… Twenty-five was the last time I stood to take a shower because I fell often. Twenty-six was the last time I walked and … stood on my own.”
- The effect of chronic pain and muscle loss on everything from eating to maintaining employment.
The resulting picture of FSHD disease burden is thorough, explicit, and compelling. And the definition of what constitutes ‘meaningful benefit’ is clear.
We've shared the report with every employee
At Dyne, where we are laser-focused on developing transformative therapies for serious muscle diseases, we’ve already shared copies of the report with every employee. We know what a meaningful FSHD therapy must do. And the same will be true at regulatory agencies when FSHD drug development programs are submitted for consideration.
These meetings are huge undertakings, and we are incredibly grateful for the individuals, organizations, resources and hard work that made this one possible. To those who contributed to this report, you did a superb job of illuminating and elevating the face and voice of the FSHD community. We applaud you for increasing knowledge and understanding for those of us working on investigational FSHD therapies. Thank you.
Hello! Thanks, it was interesting to read. I recently got diagnosed with FSHD and my shoulders and triceps were very weak. Just like you, in sixth-seventh grade … I was a basketball freak than my muscles were getting weak and 3 years later (9th grade) I found out I had it and it tore me down. I’m still going strong but getting weak over time … I’m glad there is more and more FSHD research and there is a chance that our lives could become easier. God bless those who work for a solution.
Crystalizing the patient experience through meetings like this is so very important and I thank you for this report and commentary. I’m fascinated that speech – the ability to form words – might be a valuable endpoint to target for evaluating drug efficacy. Thank you for bringing this to public attention.
Thoughts about current progress toward FSHD treatment.
There have been all of these “breakthroughs” for the last 40 years since I was diagnosed and still absolutely nothing tangible at the clinic to counteract this disease. They say, well, these breakthroughs should give you hope and that’s something. I tell you with 100% certainty that all of the hope In the world does nothing to help me walk or dress myself or live in a dignified manner.
My analogy is that I am in the sea struggling to keep my nostrils an inch above water in an epic fight to keep life worth living. The research/medical community teases that they have tested ideas in the lab that show great promise to make a successful life preserver, but it will take many years or decades, or some undefined time to get it just right before they can get it to me. I say throw me a less than perfect life preserver now rather than a perfected one later when I will surely be dead anyway. This is what we all with FSHD scream from the top of our lungs to no avail.
Here is a recent article about a “new treatment” using gapmer technology “showing promise” to counteract DUX4. So they were able to administer this into a live rat with human FSHD muscle cells and measure 99% reduction in DUX4 and larger more functional muscle cells. Great, now how many decades am I supposed to hang on clinging to something not quite death but surely not a dignified life while this idea is bantered around throughout academia in powerpoints and symposiums before something tangible happens for someone suffering from FSHD?. 10 years? 20 years? 40 years? Never?
https://www.sciencedaily.com/releases/2020/06/200629164141.htm
We needed tangible therapies years ago. We cannot wait for another 5, 10 or 40 years.
Yes I understand what is involved with FDA approval and why this is required, but there needs to be a way to make this process happen in a time frame relevant to those who are currently afflicted. This clearly is not the case now. Yes, Covid vaccine development was an unprecedented effort, but it shows that a new idea in a lab can be developed and released in months instead of years or decades or in the case of FSHD, for all practical purposes, never. Sure there was risk to the 40,000 vaccine trial volunteers, but there is also a very unpleasant certainty for society if nothing is attempted. Where in the pursuit of a FSHD therapy, is someone afflicted even involved with discussion of accepting some risk to advance therapy vs. the unpleasant certainty of FSHD if no therapy exists? Why not emergency authorization for FSHD therapeutic trial. It is very much an emergency to us and those that care for us.
Today, we have people getting full face and limb transplants when there is a 50% chance of death to do so. We have a toxic chemical in our body killing our muscles with absolute certainty and along with it killing our ability to live a dignified life. And for some reason it’s inconceivable to accept some risk or do what is necessary to get a therapeutic to the afflicted quickly.
I’m writing from Melbourne Australia.
I’ve been living with the insidious effects of FSHD since l was about 10-11. I am now 61 and have been living in aged care for nearly 10 years. Thank goodness l have wonderful care staff and a supportive family. Just typing this has taken a couple of hours.
Now, V has absolutely nailed it. I don’t know how many briefings l’ve been to where they’ve said 5 years to a treatment. That started in the early 1990’s.
Still they now say 2025. 10-20-30-40 years – l suspect it’ll be at least 25 years. I doubt l’ll be around and if l am l’ll be way to compromised for any meaningful improvement. Hope is the only thing l’ve got. I know the FSHD scientific community are doing incredible research and that meticulous research takes time. What is the risk/ reward? I keep reading about CRISPR, what’s the deal there? Same thing with AI. When l read about grants for FSHD research I never see AI mentioned – why??
It’s interesting, I’ve been thinking a little about the time lines of how quickly the Covid vaccine has been produced, tested, trialled and approved and was exactly thinking how amazingly quick it was to do. It can be fast tracked seemingly if it impacts the right people.
Don’t get me wrong. I am eternally grateful for all those scientists, researchers, grad students, admin, those people that represent us before government, those involved in research funding, those people who donate to funding research ( l’m one of them ), those FSHD sufferers who donate time and muscle biopsies, their families and friends.
I often tell people, those that are interested or even care, that l’d take a 10% improvement if they could stop it dead. I accept the fact that l’ll probably never stand balanced on my two feet let alone walk or run again. Just holding a pen to sign my name is an ordeal. I’m tired of looking up, from a wheel chair, to everyone standing around me.
One thing l notice is the long pauses between updates. I understand research takes time, but gaps of 17-20 months for ‘promising’ targets is very frustrating. What do the long research updates mean or tell us? Does ‘silencing’ DUX4, for us unique FSHD sufferers, have any profound effects on other parts of our genome considering the mysterious world of ‘junk DNA’? ls silencing DUX4 way, way, way in the future – possibly never? One of my brothers who has FSHD is extremely skeptical – l must confess l agree with him. I’m not holding any hopes. I’ll just slowly ‘disintegrate’ to a point where l have an active brain and a totally useless shell of a body. I’m ok with that, don’t like it but l’ll plough on.
I get the impression DUX4 is like a tree. DUX4 is like the ‘visible’ tree trunk. Underground are all the roots heading off in different directions. When research is carried out on one of those roots they spawn their own set of roots. Will this ever end? Is AI the secret here? Conceivably, the parent/ child hierarchy of tree roots could be hundreds of layers deep. This would cause the 10-25 year treatment ( probably not cure ) timeframe.
Thanks for reading from ‘down under’.
Gerry, I am sure most people with FSHD are more or less infuriated with the total ineffectiveness of the medical establishment to provide a treatment for fshd in any meaningful time frame. Sure there may be various :roots” pathways to cell death from DUX4. And the current development process to target these is serial rather than parallel and each iteration takes years. 20 years might get you 3 or 4 iterations. Consider the idea that a muscle cell growth stimulator may be needed along with DUX4 suppression. My guess is that even though each of these will have been tested separately in the near future and maybe without significant effect separately, but to test the combination would require another ridiculous multi-year long drawn out process. The people with HIV/AIDS basically revolted against this system in the 1990s, took matters in their own hands and used drugs and combinations not approved to save themselves.
This ,in the end, trimmed years if not decades off successful therapies for HIV/AIDS.
It’s so ridiculously ironic to hear about all of the years that are needed to do safety studies on some of these potential therapies as if DUX4 induced muscle cell death is some kind of a safe alternative. Consider Fulcrum’s 1 year phase 1 for a repurposed drug that had already been successfully safety tested on 3500 people previously. They are so worried that this may be unsafe for us with fshd we have to wait another year to safety test a drug that had already been safety tested. Same with this starfish testosterone/rHGH study. The safety profile of these is already known and I could already be taking these for other conditions at the same time regardless of having fshd or not. Is there any wonder why many with fshd are infuriated and disgusted with the medical establishment. I think infuriation and disgust with the medical establishment would be the prevailing voice of those afflicted with fshd.
Gerry, the only thing more infuriating than the impact of the FSHD disease on your body is the total lack of effectiveness of the medical system to get a treatment to those that suffer from it in a relevant time frame. I think most people with FSHD, for good reason, feel totally let down by this system and that’s why most do not “engage” with it. Doing everything possible to avoid thinking about this horrendous disease when you can is less infuriating than “engaging” the system and reading about how science can fix this in a mouse model multiple ways but it will be many years or decades until these ideas will be used to treat a human if at all. Facio Therapies a few weeks back had a “5 years to a therapy” banner on their home page. I asked them what that meant as I am interested to see if there is anything beneficial on the horizon relevant to the time frame of my life. Does this mean 5 years to get something preclinical into a mouse model? 5 years to an IND filing? 5 years to commercially available? 5 years until I could have access during trials via expanded access program for those severely affected? I asked about the 5 years itself. Does that means 1Q26? If I look at the web site 6 months from now and it says 5 years isn’t that different than when I look at it now? They wrote me back and said they are not far enough along to make a prediction about the time frame of their program. I also looked at their web site recently and there is no mention of 5 years anymore.
FSH Society had a 5 year count down going on their home page which, unlike Facio, at least had an actual end date. But now I see no count down. 2025 is still mentioned for now. Let me give you an example of why I am cynical.
There currently is a trial testing testosterone with rHGH(human growth hormone) in men with FSHD. The first documents for this trial were written in 2017 and phase 1 trial will not be completed until this year. Really? 4-5 years to test known, readily available compounds with well established safety profiles? And we are supposed to believe there is some kind of urgency to find a treatment for FSHD?
Like you, I appreciate the individual efforts of those working on this. I also see the absolute possibility of science getting to an effective therapy, but unfortunately, I see a system that is totally ineffective and cumbersome and likely will not produce tangible results in the time frame relevant to most of us who are currently alive and suffer from this.
Hi V………can l ask a couple of personal Qs? How long have you had FSHD and are you still walking/ standing?
Not sure if giving a time frame is a help or hinderance. Probably helps if you’re newly diagnosed. Definitely a frustration for those who have followed the news and trials for many years. Get all excited about some breakthrough then nothing. I’ve learned to take things as they come.
Regarding the testosterone with rHGH (human growth hormone) trial, you need to be able to walk 6 metres. No good for me, l’m wheelchair bound.
About research, have you been following ‘CRISPRoff’ – now that’s really interesting. Try this site New, reversible CRISPR method can control gene expression while leaving underlying DNA sequence unchanged (phys.org)
Keep your head up – is what it is……….Gerry
40 years, no longer walking
The point about testosterone/rHGH is that the trial is taking many years longer than it could or should. And this is for a simple, widely used already known compound.
Walking is a criteria for the trial since it is possible/easier to measure changes to walking performance and this would be a direct functional benefit. If the trial was successful, at some point, the therapy would almost certainly benefit and be available to all adult males with FSHD regardless of severity.
Outstanding blog post! Dyne truly understands the patient community. Thank you!
A very important topic. I think it is very important for people with FSHD to share their problem with other people with the same diagnosis. Undoubtedly, scientists are working on an effective treatment, but if only it were that simple.
I hope with each development the therapy will become more and more effective and efficient.