Tag: MLD

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Advocacy Awareness Clinical Care General Research Therapies

MLD Gene Therapy Approved in Europe

MLD gene therapy approved in Europe banner

Gene therapy for early-onset MLD patients has been approved in all 27 EU member states as well as the UK, Iceland, Liechtenstein, and Norway for early-onset (late infantile and early-juvenile) patients.

Congratulations to the San Raffaele, TIGET, and Orchard Therapeutics teams, the clinical trial families, and the entire MLD community on this significant milestone! MLD Foundation first started working with the San Raffaele/TIGET researchers in 2005 and has been fully engaged and actively supporting the project throughout its pre-clinical phase and subsequently nearly a decade of human trials. The results in the target patient population have been outstanding. We are excited to continue on the journey toward approval & access across the EU … and throughout the world.

Dean Suhr, President & Co-Founder, MLD Foundation

Following the receipt of a European Medicines Agency (EMA) positive opinion last November recommending full marketing authorization for Libmeldy™, the gene therapy becomes the first gene therapy for eligible patients with early-onset MLD, and MLD’s first commercial therapy.

LATE-INFANTILE & EARLY-JUVENILE FORMS

Presymptomatic late-infantile and early-juvenile forms of MLD are included in the approval. The approval also includes early-juveniles with early clinical manifestations (symptoms) who are still able to walk independently and have not started to decline cognitively.

OTHER FORMS of MLD … and ACCESS IN OTHER COUNTRIES, INCLUDING THE USA

Orchard has a clinical trial underway studying Libmeldy in the late juvenile form of MLD, however, it should be noted the late juvenile and adult forms are not covered by this commercialization approval.

Patients outside the EU and with later-onset forms of MLD are able to request Orchard for access to Libmeldy via Orchard’s Pre-Approval Access/Compassionate Use programs. Orchard reviews each request on a case by case basis. MLD Foundation will help you advocate for access for your loved loved ones.

THERE IS STILL MUCH LEFT TO DO

Access and reimbursement … EMA and EC approval is a huge milestone, but it is not the finish line. MLD Foundation will continue to work directly with Orchard, EU partners, and country officials as each EU member country undertakes its own Libmeldy price and reimbursement review to make the therapy formally made available to its citizens.

FDA (USA) … MLD Foundation has been in communication with the FDA and is in full support of Orchard’s IND activities that we expect will lead to a BLA request for review and eventual approval in the US.

Newborn screening … MLD Foundation is leading an MLD newborn screening development, validation, and implementation effort to identify patients pre-symptomatically. We need your participation to make this effort successful. Click here to learn more and join us!

Subscribe to this blog to be kept updated on gene therapy and other therapeutic advances, and ongoing efforts to improve other aspects of MLD quality of life.

Orchard Therapeutics Press Release

* Libmeldy is the EU commercial name for the gene therapy and is a trademark of Orchard Therapeutics.
* The image on this page is a screen capture of Orchard Therapeutic’s homepage featuring one of the first MLD gene therapy patients.

Categories
Action Alert Compassion General

Giving Tuesday – It’s Our Day

Did you know that today, Tuesday, December 1st, is Giving Tuesday?

After a month of “Black Friday” and yesterday’s “Cyber Monday” frenzy, it’s a day to focus on our loved ones!

We aren’t asking for your donations …

MLD Foundation knows that MLD families have their hands full with their loved ones so for the past two decades we’ve made it our practice to not directly ask you to be our primary source of financial support.

But with that said, we are so thankful for the many families over the years who have organized events and fundraisers … and we are so humbled to be remembered when loved ones get their angel wings.

We are asking you to please share with your friends, extended family, …

Today we’re asking you to share with your extended family, friends, neighbors, co-workers, and social networks how important and impactful MLD Foundation has been to your family. We need your help to ask for their support!

How we use donations …

We are frugal with all donations … they go directly to expenses surrounding our core We C.A.R.E.™ mission …

We C.A.R.E.™ … Compassion for families, increasing Awareness, influencing & funding Research, and promoting Education for metachromatic leukodystrophy, a very rare terminal genetic neuro-metabolic disease where over half the cases affect infants.

Since our founding, we have not had any paid staff, all of our work has been a labor of love … no donations have gone to salaries.

2021 will be busy and productive

As we highlighted in last week’s Thanksgiving blog, 2020 has been a very productive year, and 2021 is looking to be the same.

We have a major multi-year project underway making newborn screening a reality for all families worldwide so children have the broadest and optimal choice of therapies while their loved ones are pre-symptomatic and therapies are most effective.

But that’s not all – we are working to assure access and reimbursement for the gene therapy emerging in the EU, we’re supporting the submission and review of gene therapy by the FDA in the USA, increasing physician and family awareness, improving clinician education, developing an MLD Standard of Care, and supporting a number of new therapies in development and under clinical trial at nearly a half dozen biopharma companies, and so much more.

Please share … a few moments of your time will allow us to to keep serving you!

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Compassion General

We’re thankful – even in 2020!

We heard earlier this week that nearly 4 in 5 people are already looking forward to putting 2020 behind us. The pandemic (family safety, work, school, loss of loved ones, individual and community response, social isolation, etc.), US elections, income, health, … it is affected every one of us, and it’s overwhelming.

But we are still thankful…

… not for MLD, not for loss, but for all of you – our friends, family, the MLD Family™, the greater MLD community, the MLD researchers and clinicians, regulators, policymakers, and the rare disease ecosystem who supports us.

The MLD Family™ …

… is supporting each other. There is advice, compassion, and the sharing of excess or needed supplies. We can’t meet in person, but we’re connecting with regular men’s, women’s, and now couple’s calls and so much more as we adapt to new ways of connecting.

MLD Research is progressing …

Orchard Therapeutics has achieved EMA/CHMP recommendation for approval of gene therapy in Europe. They have also filed an IND with the US FDA, a key stepping stone formalizing communications with the FDA as they move one step closer to US review and approval.

Takeda continues its ERT clinical trial. Homology Medicine continues to make pre-clinical progress with their gene therapy. And we are working with several other biopharma companies, too!

MLD Newborn Screening …

We have to diagnose children earlier in order for them to have good viable life-saving therapy options!

The MLD Newborn Screening program is making great progress. New York is right on the cusp of launching an MLD pilot study into parts of their state. The MD NBS Expert Advisory Group is meeting monthly. Many of you are participating with the Working Focus Groups – you can still join us for our December meetings!

MLD Cinical Care Continues to Improve …

We are blessed to have many wonderful and knowledgable MLD clinical researchers … we still need more, but those who do support our community are open, supportive, and often go the extra mile as they care for our loved ones in person or remotely. We worry about their health as they are called into care situations where additional COVID resources are necessary – let’s all keep doing our part to keep these COVID care needs minimized and our clinicians safe!

In 2020 we started to lay the foundation for creating an MLD Standard of Care so we can all more easily get approval and reimbursement for better, more consistent, and more appropriate MLD clinical care.

Let’s keep connected …

Subscribe to this blog to be kept updated on therapeutic advances and ongoing efforts to improve other aspects of MLD quality of life.

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General

Gene Therapy Recommended for Full EU EC Marketing Authorization Review

Gene therapy for early-onset MLD patients passed a huge milestone yesterday when the European Medicines Agency (EMA) Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion recommending full, or standard, marketing authorization for Libmeldy, by the European Commission (EC), which has the authority to grant marketing authorization for Libmeldy* in the European Union (EU). The EC is anticipated to make a final decision by the end of 2020. If approved, Libmeldy™ would be the first commercial therapy and first gene therapy for eligible patients with early-onset MLD.

LATE-INFANTILE & EARLY-JUVENILE FORMS RECOMMENDED

Presymptomatic late-infantile and early-juvenile forms of MLD are included in the recommendation. The recommendation also includes early-juveniles with early clinical manifestations (symptoms) who are still able to walk independently and have not started to decline cognitively.

THERE IS MUCH STILL LEFT TO DO

After the EC marketing authorization is approved, each EU member country will have to do its own Libmeldy price and reimbursement review before the therapy is available to its citizens.

MLD Foundation is leading an MLD newborn screening development, validation, and implementation effort to identify patients pre-symptomatically. We need family participation to make this effort successful. Click here to learn more and join us!

Subscribe to this blog to be kept updated on gene therapy and other therapeutic advances, and ongoing efforts to improve other aspects of MLD quality of life.

Orchard Therapeutics Press Release

* Libmeldy is the EU commercial name for the gene therapy and is a trademark of Orchard Therapeutics.

Categories
Advocacy Awareness Compassion General Policy Research

Capitol Hill, BIO, 21st Century Cures, Airbnb, and one more thing … Reflecting on my DC week

The first rule of blogging is to post good content on a regular basis.  The second is to keep your posts short, to the point and to not mix multiple topics into one post.  Oh boy, am I in trouble …
jetitup2016-11
My 6th trip to DC this year ended reflecting at 35,000′ with a Crater Lake Hazelnut Espresso Vodka courtesy of gold status on Alaska Airlines as I flew non-stop back home to Portland Friday evening.

Icratelakevodka admit I was stoked because of so many good people, connections, meetings, and events that I had experienced over the past three days.

And then I connected to Alaska’s WiFi …

Before I tell you what I learned from the world below,  let me share a few of the other highlights … each of which I will share much more about in coming posts.

13 Senate ofice meetings in one day

Jay Griessing of Biomarin set up and attended 14 Senate us-senateoffice meetings and one House meeting with me … 13 Senate meetings on Wednesday alone!  I have been to Senate offices many times over perhaps a decade – my prior max was 6 or 7 meetings. And better yet, because Congress is in recess (out campaigning) the two of us were very efficient as we meet with the staffers who do the real work on the Hill.

21st Century Cures is alive

curesnowpictWe discussed 21st Century Cures, its history and what we hope to accomplish over the next few weeks during the lame duck Congressional session.  The short update … there is a lot of enthusiasm on both the Senate and House side to get #CURESnow passed.  It might be slimmed down a bit but we’ll take it.

Rare Policy

rarepolicy-home-pages-draftA missing voice was identified at 21st Century Cures strategic planning meeting held two weeks ago duringmy 5th trip to DC at the NORD Rare Disease Summit.
We need the voice of the patients, families, caregivers, and general public to push CURES to the finish line.  I am about 24 hours away from launching a platform that lets this audience contact Congress with 1-click in a much more impactful way … and gives those of us managing these programs a lot more ability to build on these grass-roots networks.  I spent three late nights last week communicating with a development team in India … and watching the Cubs historic win streamed to a small corner of my screen.


BIO Patient & Health Advocacy Summit

biosummit2016I again attended this annual gathering of advocacy and industry. The #BIOsummit2016 sessions and particularly the networking was exceptionally rich this year.  BIO does great job of balancing the content and attendance so we all come away enriched and informed.  I spent time with dozens of people from multiple stakeholder communities … advocacy, industry, policy, organizational leadership, consultants, communications, etc.

Airbnb

airbnd-chic-14th-uairbnb-new-logo-1-1024x863Ok , I’m adventuresome, frugal with MLD Foundation funds, and we’d reached our quota of room nights with Hilton family hotels to keep our status with them … so I made my first Airbnb reservation and stayed at a place described as Chic designer-rustic, 14th & U Neighborhood, Metro (if you sty there tell them Dean recommend you).  A 3rd floor room, a tiny European style bathroom with a sideways sink, WiFi and great hosts.  I’m no longer an Airbnb virgin.

And then …

edengetsherwings201611One email subject line whisked me from this whirlwind activity, progress, and networking and reminded me of the reality of why I’m doing this … “Eden gets her wings”.  Beth is not a MLD carrier and Eden was healthy by all accounts when she was adopted from Ethiopia by her single mother, Beth.  7-year old Eden was finally free from MLD, but no longer with us.  Late infantile MLD starts to show its devastation around 18-24 months, just after Eden was brought to the US to live what was supposed to be a happy healthy life.

#FMLDfmldcar … which properly stands for Fighting MLD … but that’s not quite how I feel right now.  ;(

I love what I do … and yet I hate the reasons I ever had to start doing it.  MLD and Rare Disease are my passion and focus … but there are times where overall health and sometimes even bigger things are the concerns.

more to come …

Categories
Awareness Education General

80% of Rare Diseases are Genetic

80% of the 7,000 Rare Diseases are genetic in nature.  80-are-genetic---February-is-Rare-Disease-Month

While most rare diseases show symptoms early in life, many are later onset diseases because our genetics are always with us.

Genetic inheritance patterns can vary from single gene autosomal recessive (like MLD) where 50% of offspring are carriers, 25% are affected, and 25% are free of the bad genes entirely … to autosomal dominant where 50% of offspring have the disease … to several forms of X-linked where which parent is affected and the sex of the child determine the inheritance pattern … or inheritance can be a more complicated multifactorial pattern that includes genes and environment … and there are mitochondrial inheritance patterns as well.  Learn more about forms of inheritance here.

Autosomal Recessive

It is important to note that carriers, while most often not sick, can pass along carrier or affected status if their spouse/partner is also a carrier.  Very rare diseases like MLD have a frequency of 1 in 40,000 births, but note this equates to 1 in 100 of the general population being a carrier.  That’s one carrier in every 3 or 4 school classrooms, 2 or three carriers in every movie theater, and about 685 carriers at this Sunday’s Super Bowl (68,500 seats)!

 

 

Rare Facts – what we’ve learned so far …1 in 10 - February Rare Disease Month square

1 in 10 have a Rare Disease.
over 7,000 Rare Diseases … 30 million Americans, 30 million Europeans, 350 million world-wide are affected by Rare Disease.
80% of Rare Diseases are genetic.

rdd-logo-transparent-small
February is Rare Disease month, culminating on February 29th – a Rare Day indeed – which is Rare Disease Day.
Stay tuned for month of Rare Disease facts, tidbits and things to know.

Sign up to follow this blog and be sure to share this post.

Categories
Awareness Clinical Care Education Research

Are normal enzyme levels enough to stabilize MLD?

A very interesting question came up today on the MLD Family Discussion List™ (a private list we run for MLD primary caregivers).  I thought it might inspire some thinking so I am sharing my answer here as well:

I have a question and I don’t know if anyone has an answer but I am wondering if anyone knows what truly stops this disease? Is it a normal enzyme level? Will the kids stop declining if the enzyme level stays normal? Are there other things that contribute to the stabilization of MLD?? 

Your first guess is actually correct – we really don’t know.  It will take lots of years of careful study looking at extended clinical trial/Phase III data, combined with more basic science bench work, natural history, and lots of patient & clinic reported progression/outcome data to really understand this disease.  And on top of a basic understanding we have hundreds of mutations to study.  We’re not planning on shutting down the MLD Foundation anytime soon!

From a practical perspective, the generally accepted consensus is that if the enzyme level in the blood is high enough (remember that “normal” levels vary all over the map and carriers with low blood enzyme levels appear to be metabolically “normal” people) then MLD’s progression will be dramatically slowed or halted. There is truth in this first order basic assumption – but it’s just the start of our understanding.
However (and not to scare you), there are three things to consider as we peel the MLD onion one layer (and there will be more subtleties as we further peel the MLD onion again in the future):
1) The first is that enzyme in the blood is of no value – it needs to be in the nerve cells that need it. Today’s therapies are primarily focused at crossing the CNS (central nervous system) into the brain. We measure enzyme levels in the blood and the CNS because it’s possible – brain biopsies on living people are not good! The state of our ability to get enzyme’s  large molecules reliably across the blood brain barrier (BBB) is in its infancy and the results are inconsistent at best.  The Milano gene therapy acknowledges this challenge by trying to make sure that whatever gets across the BBB produces 5-10x more enzyme than is typical hoping that the overproducing cells will share enzyme with their neighbors. Think of a gas tank in a car – a full tank shows “F” on the dial, but the engine won’t run if the fuel filter (BBB) is blocking the gas from getting to the engine (the brain).
2) The second thing to consider is once enzyme gets past the BBB will it get to all of the cells that need it?  Are some/many of those cells already compromised or unreceptive, does the enzyme (actually it’s a protein) get distributed to all regions of the brain, are the cells fixed so they keep on producing the enzyme or are they waiting for anther infusion like Enzyme Replacement Therapy (ERT) is designed to provide?  To continue the car analogy – the car may run if only 3 cylinders (brain regions) get fuel (enzyme) but you really need fuel to get to all of the cylinders (regions of the brain) to have the optimal/desired performance.
3) As mentioned, today’s therapies are primarily targeted at the brain/CNS, but our nervous system has a second component, the Peripheral Nervous System (PNS) that needs to be “fixed” as well.  The PNS makes sure the messages from the brain/CNS get to the muscles and systems elsewhere in the body.  We have historically seen a lot of transplants where the brain progression is slowed (stopped?) but the motor skills continue to decline (witness the many post-transplant children in wheelchairs).  The PNS is slightly different in its makeup than the CNS.  It also has a barrier, sometimes called the Blood Nerve Barrier (BNB), which is different from the BBB.  The common response when we ask why current research is focused on the CNS and not the PNS is that it makes sense to prioritize the CNS.  The challenge is that, to our knowledge, very little work has been done on the PNS barrier aspects of MLD. The car analogy is when the engine is running but the car is in neutral – lots of power under the hood but it is not getting to the wheels (limbs & organs) so the car is not going anywhere.
Also remember that some of these therapies require time to take hold.  The transplants need to engraft and the “good” cells take over/replace the bad cells before they can be effective. With ERT the thinking is they need to maintain somewhat consistent levels in the CNS which drives dosages and frequency of infusion.  Different issues, progressions and concerns will be at different priorities during the various early and long-term phases of each therapy.
And there are other therapies being developed as well … what if we reduced the amount of sulfatides produced so the little bit of enzyme that many MLD patients have doesn’t have to go as far?  This is called substrate reduction therapy (SRT) and hopefully will require a small molecule which, like alcohol, can more easily cross the BBB.  In the car analogy we still only get a little bit of gas through the clogged fuel filter – but what if the car was lighter and didn’t require as big an engine – their might be enough fuel getting by to be able to get from point A to point B?
We don’t have to completely understand all of this to make progress and see results in therapies.  As I mentioned above, the studies will go on for many more years and hopefully, today’s therapies will be good, tomorrows will be better, and in 5 or 10 years they will be even better as we better understand MLD, the body systems and the therapies of today and the future.  But for tomorrows therapies to be optimal, we do have to take the time to learn from every patient, every success, every valiant effort, every failure, and to explore every creative idea – many of which will lead us to increased knowledge even thought they are a practical dead-end.
At our upcoming Board meeting we are going to talk about investing in an independent formal MLD Registry to start to capture this scientific and medical history data in a more accessible scientifically managed database – we want the data to be there for future researchers to study when they have a creative idea.  And by investing, I don’t just mean a few dollars,  I mean that all of us, all of the MLD patients and their families, will be asked to contribute data as we begin to crowdsource MLD research in ways bigger than just one isolated project after another.