[michael-morale]

Lupa –

You actually pose a very good question with regards to the data. Even though no formalized data has been released, Scholar Rock has mentioned on quite a few occasions about how muscle targeted therapies will help those of us with SMA.

All of us know that Spinraza and Evrysdi both work at the cellular level, and while there was a lot of hope and anticipation that this would allow us to get stronger, both of these treatments do not address previous damage that has already taking place in our bodies. These treatments will either slow the progression or possibly stop the progression from getting any worse, but until a muscle directed targeted therapy is passed by the FDA, this is the only thing that we have to work with.

Being that SRK-015 is the first muscle targeted therapy, all of us are hoping that it will allow us to actually build muscle mass. If this actually comes to fruition, I’ve heard from numerous people that this could be our greatest chance at a combination therapy. If we could take Spinraza or Evrysdi, which work at the cellular level, and also take SRK-015, which works at the muscular level, this will give all of us who suffer from SMA the greatest chance at possibly building muscle mass, and we may even begin to see some repair from previous damage that had already taken place in our bodies.

I hope this explains it a little bit better, and feel free to let us know if you have any other questions. Thank you.

[michael-morale]

Teri – I’ve never really heard of children suffering from seizures with regards to their Spinraza injections, but if your son didn’t have seizures before starting Spinraza, there may be a correlation.

I agree with Alyssa when she said that risdiplam will be going to a different part of the body. Since risdiplam is going to be an oral treatment, that can also be administered through a G-tube, you might see a difference, but I would definitely talk to your son’s pediatric neurologist. I’m hoping that we hear something in the next few weeks with regards to the FDA decision regarding the approval of risdiplam.

Please keep us updated, and let us know if we can help in anyway.

[michael-morale]

Lupa,

I’m glad that your procedure went well. It can be somewhat unnerving to be too close to people that have tested positive. When my caregiver dropped me off at the hospital, I had to have my mask on, and I had to go through 2 different checkpoints before I was admitted into the hospital itself.

When I got to the registration desk, they a bulletin board with a phone number that we had to call. When I called this number, they checked me and over the phone and then came out and took me to my room. All the doctors and nurses were in their PPE’s, and everyone was taking the necessary precautions that they needed to.

Let me know if you have any other questions, and have a blessed day.

[michael-morale]

Hey Alyssa,

Everything went well. I went into the hospital about 10:45 AM, and after the procedure was completed and I had one hour to lay on my back, I was released from the hospital around 3:30 PM CST.

Hope you’re doing well, and have a blessed day.

[michael-morale]

I personally don’t think that this would be considered as receiving a combination therapy. You are correct when you say that this was one of the prerequisites, and the example that I gave you regarding the gentleman that I know that had been on Spinraza and then moved to risdiplam in January 2019 is an example of this.

I don’t believe that any of these treatments, such as Spinraza and Zolgensma, and possibly even risdiplam, once it’s approved, will be used in conjunction with each other at the same time. I know that there is a time limit that you have to be off of Spinraza before you can start risdiplam, and I’m sure that this will be the same stipulation once the FDA approves risdiplam and writes the label. My understanding at this time is that you are only allowed to be on one specific treatment at a given time.

There has been conversation regarding risdiplam possibly being used in conjunction with another treatment, but at this time, the pharmaceutical companies and the medical establishments have not said for certain as to when or if this will happen. If it does eventually happen, then I think this would be the first reported combination therapy.

Again, I apologize for my long-winded response to you last night. Please let me know if you have any further questions, and have a great day.

[michael-morale]

Mike – I’ve never heard anything regarding a combination trial, and I personally don’t think that this would be an option during any clinical trial setting. I say this because during all clinical trials, the pharmaceutical companies are testing the efficacy and safety of a certain treatment that is trying to get approval from the FDA. I don’t see the FDA allowing someone to be on 2 clinical trial treatments at the same time, because this would negate any ethical data that they are trying to collect. They wouldn’t want one clinical trial treatment counteracting another clinical trial treatment, so I personally don’t think that this would be an option that would be available to anyone, solely based on efficacy and safety.

Now, when it comes to the definition of what a combination therapy would be, I’m still at a loss for words regarding the true definition. The true definition of what a combination therapy would be, would have to come from the FDA and the pharmaceutical companies, and since there are no actual combination therapies out on the market as of yet, I’m having trouble finding a good definition as to how they would define what a combination therapy would be. Let me explain:

===================================================

• Are they going to classify a combination therapy as being on 2 different treatments at the same time?
• Are they going to classify a combination therapy as having been on one therapy for a given amount of time and then switching to another therapy.

===================================================

If they define a combination therapy as having been on one treatment for a given amount of time and then switching to another treatment, then I guess you could say that I’m going to be on a combination therapy myself, given the fact that I’m going to be switching from Spinraza to risdiplam in August after it’s approved by the FDA. I personally don’t think that they would classify my situation as being on a combination therapy. (I would think that you would have to be on 2 FDA “approved treatments” at the same time to be on a combination therapy, but that’s just my logic.)

As I mentioned in a previous post to you, Scholar Rock is working on their potential treatment known as SRK-015, which will work on the muscular skeletal issues regarding the ability to grow muscle mass. Both risdiplam and Spinraza work on the cellular level by correcting the SMN2 gene deficiency in producing protein. I see the possibility of these 2 treatments working together as a possible combination therapy, but again, this is something that still hasn’t been decided as of yet.

The person that I know that is part of the Jewelfish trial was on Spinraza when it first came out, but then switched to risdiplam during the early part of 2019. I don’t think this was considered being on a combination therapy, because I think he had to be off of Spinraza for a given amount of time before he could start risdiplam, and since risdiplam has not yet been approved by the FDA, I don’t think this would be considered a combination therapy.

Regarding Zolgensma, I’m not really sure if any of these clinical trial participants had been on any other trials or treatments while receiving Zolgensma at the same time.

I know that this was a lot of information to try to absorb, and I apologize if I made the waters even more muddy than they already are.

[michael-morale]

Crystal –

My name is Michael Morale, and I’m the Senior Director of Multi-Channel Content for SMA News Today, along with their parent company, BioNews Services.

I read your comments about the pain that you’re going through with regards to your buttocks and your tailbone. I wanted let you know that there are so many of us that are going through the same issues, and I wanted to let you know that you’re not alone. I can give me some suggestions that I’m trying to help eliminate these issues, but please remember that these are just my suggestions.

• About 3 years ago, my buttocks started to hurt during the day, while I sat in my wheelchair, and this discomfort was never a problem until that time. I went to countless doctors, and went through a few CT scans to try to determine what the problem was, and after numerous tests, they told me that I had lost most of the fat and muscle in my right buttocks, which I guess they call the gluteus maximus. Essentially, I was sitting on nothing but bone and nerves, and this caused severe discomfort not only in my buttocks, but also in my thigh and calf in my right leg. I spoke to my physical therapist about this, and they did quite a bit of stretching and range of motion exercises in my right leg, which over the course of time, has definitely helped. If you are taking physical therapy, I would speak to your therapist about this to see if they can maybe stretch your hips out just a bit more and possibly work on the range of motion.
• Try different cushions in your wheelchair as well. Instead of sitting on foam, try a cushion that is made from an air bladder, which is called a Roho cushion, or maybe try a cushion that has a jel insert. I’m going to be trying a new cushion that has a jel insert in the next couple weeks. They say that this will help disperse some of the pressure in your hips and your buttocks. I haven’t had a chance to try one yet, but everyone that I’ve spoken to you so far, has said that they work really well. By dispersing the weight on your tailbone, this might help relieve some of the pressure and the pain that you feel. If you have a physical therapist, speak with them about these suggestions, and if you work with a wheelchair company, see if they can provide you with a sample cushion that you can use to test out before you purchase one. By the way, most insurance companies will cover the cost of a new cushion every year, so check with your insurance company as well.

I hope these suggestions will help you.

[michael-morale]

Hi Mike – The NCT number that you gave, (NCT03032172), An Open-Label Study to Investigate the Safety, Tolerability, and Pharmacokinetics/Pharmacodynamics of RO7034067 in Adult and Pediatric Patients With Spinal Muscular Atrophy, is the Jewelfish trial that started back in January 2017.

If you go to http://www.clinicaltrials.gov and enter the NCT number in the search box and press enter, it will bring this trial up and give you all of the latest information regarding where they stand. (Here’s the link that you can use to get to this clinical trial. If it’s not an active clickable link, just edit/copy the link and edit/paste it in your web browser and press enter:  https://www.clinicaltrials.gov/ct2/show/NCT03032172?term=NCT03032172&draw=2&rank=1 )

I don’t believe that this is a combination therapy trial, or at least that’s my understanding of it. Hopefully, later today, I may be speaking with someone who has been part of this Jewelfish trial since January 2019. I’m going to ask them questions, but they may not be able to answer too many questions, given the fact that they may have had restrictions put on them with regards to the amount of information that they can divulge. I will definitely ask if this clinical trial was part of a combination therapy trial, but I don’t believe it was.

If I can speak with this individual later today, I will definitely respond back to you with any information that they give me.

[michael-morale]

Lupa –

It’s probably been within the last 6 to 8 months that I started noticing some strength differences in my hands, and while I do believe that Spinraza has slowed the progression of my disease, it hasn’t stopped the progression totally. I’ve talked to other people who have said the same thing regarding their condition, and given that this is the natural history of the disease itself, I’m very thankful that Spinraza has at least slowed the progression to where I’m not getting as weak as quickly as I used to.

If you watch my videos, I’m a huge advocate of physical therapy, and I do believe that my PT has definitely helped me with regards to my breathing and my overall energy level. When I went for my last pulmonary function test, PFT, my pulmonologist did say that my levels increased by nearly 6 points, which to him, was a huge improvement. He said they normally see improvements of either 1 or 2 points.

Regarding insurance, and the possibilities of them approving a combination therapy between 2 different treatments, this will be a question that the insurance companies along with the medical professionals will have to consider. I do believe that they will have to consider this, and in my opinion, they may have to consider it in the not so distant future. I’m sure that if and when this comes up for discussion, the pharmaceutical companies and the insurance companies will have to work together to come up with a viable solution regarding the costs. Right now, I don’t see insurance companies paying for a combination therapy, but then again, I’m not privy to all of their information along with the information that the medical professionals are providing these insurance companies. I do think it is a definite possibility that this will happen in the future, but then again, I broke my crystal ball the other day, LOL….

Thanks again for your comments, and please let us know if you have any further questions. We will do everything in our power to give you not only the information that you want, but the information that you need to make your life better. Have a blessed day.

[michael-morale]

Derek –

I greatly appreciate you commenting on my video. My name is Michael Morale, and I’m the Senior Director of Multi-Channel Content for SMA News Today, along with their parent company, BioNews Services

We just recorded a podcast where we did a roundtable discussion, and the subject of a combination therapy was brought up during this recording, which will be available on Tuesday, July 7.

I can tell you that there is some interest with regards to a combination therapy, but at this time, it’s still a subject that they are trying to decide on. Spinraza and risdiplam both work by addressing the protein deficiency in the SMN2 gene, and it’s unlikely that a combination therapy of these 2 treatments would be a viable option.

Scholar Rock is developing a treatment of their own called SRK-015, and while it may be a couple of years before they get FDA approval, I could possibly see a combination therapy of their treatment alongside either Spinraza or risdiplam. SRK-015, which will probably be renamed in the future, addresses the Myostatin levels in the bodies of people that have SMA. Myostatin is a growth inhibitor, and this inhibitor keeps us from building muscle mass. This is purely speculation on my part, but if they did a combination therapy between SRK-015 and either Spinraza or risdiplam, we would have something that works on both the cellular level and the muscular level. I know that there’s a lot of excitement around Scholar Rock’s potential treatment.

Regarding whether or not insurance companies would pay for both therapies is still a question that needs to be answered. This will probably boil down to whether or not the medical professionals would see a potential benefit to a combination therapy. I do believe insurance will pay for risdiplam, if and when it gets approved by the FDA sometime in August. I feel confident in saying this, because they are already paying for Spinraza, and most insurance companies have had enough time to go through the research and data, and they know that these treatments are beneficial for those of us with SMA.

This will definitely be a topic of discussion over the coming months. I apologize for the lengthy explanation, but I wanted to make sure that I gave you all of the information that I had. If you have any further questions, please feel free to reach out, and we will do everything in our power to help you.

[michael-morale]

Risdiplam, in my opinion, is going to be a major player within the SMA community. Even though it will work on the SMN2 gene, similar to Spinraza, the opportunity that it provides those who are unable to take Spinraza due to medical conditions, could give these individuals the ability to start on a viable treatments for SMA.

Some of the advantages of risdiplam will be:

1. It will be an oral treatment versus an intrathecal injection.
2. There will be no hospitalization involved in the dosing of risdiplam.
3. Patients who agree to take risdiplam will be getting a dosing every day, versus an injection every 4 months.
4. Quite a few patients who are on Spinraza, experience weakness and/or a slight lethargic feeling as they get closer to their next injection. There are hopes that since risdiplam will be a daily dosing, our bodies may not experience this lethargic feeling, because our bodies will be getting a constant supply of this treatment on a day-to-day basis, versus having to wait for months.

As we get closer to the decision from the FDA regarding risdiplam, we may start seeing more information being released, but usually, the FDA restricts the amount of information that can be released until the FDA approves or denies the treatment.

[michael-morale]

While growing up, my parents always taught me that the animals that we had as pets were more than just pets, they were part of the family. They taught us the value that these animals bring, and by doing so, my brother and I never looked at them as animals, we thought of them as family members. While I’ve lost numerous pets in my life, I’ve never had one suddenly passed away like DeAnn did.

I’m so sorry to hear about your loss, and just know that you and your family are in my prayers. Nothing that I can say can ease the pain, but just know that I’m here if you ever want to talk.

[michael-morale]

Pawel – Cure SMA might be a good place to start, but you will want to make sure that you let them know that you live in Poland. They may be able to direct you on who you should speak to.

I hope that everything works out for you, and please keep us updated.

[michael-morale]

Pawel – My name is Michael Morale, and I’m the Director of Multichannel Content for BioNews Services, the parent company of SMA News Today. I wanted to take a few minutes and try to possibly answer some of your questions and concerns. First, before I began, the ultimate decision to switch from Spinraza to Zolgensma, needs to be made between you and your child’s pediatric neurologist. I’m not sure what the medical situations are in Poland, given the fact that it is a public health care type system, but my recommendation would be the same as what Kevin told you in his response regarding trying to find a doctor that has some working knowledge of both Spinraza and Zolgensma.

Zolgensma is only approved for infants and toddlers 2 years of age or younger, irregardless of the type of SMA that they have. Like Kevin, I too am on Spinraza. While I haven’t seen a great amount of muscle strength improvement in my arms, I do feel that Spinraza has halted the disease process, because I am not getting any worse. I’m now actively taking physical therapy and we are working on core strengthening exercises to improve not only my core strength, like my abdominal, back, shoulder and neck muscles, it’s also greatly improved my balance while sitting in my wheelchair. My breathing is exponentially better, but I’m not really sure if this is caused from Spinraza or my physical therapy.

Regarding your son Alex, I understand that he just received his 3^rd injection of Spinraza. You need to understand that each person is going to react differently to this treatment. Some infants and toddlers will show more improvement than others, while some, may not show as much improvement in the same amount of time. You had mentioned something about a combination therapy between Spinraza and Zolgensma, but scientists and researchers are finding that this really is not showing any beneficial effects. Zolgensma works by replacing the SMN1 gene, and Spinraza works by repairing the SMN2 gene. These are 2 totally different approaches, because Spinraza is a cellular-based therapy while Zolgensma is the first FDA approved gene therapy.

Like Kevin stated in his follow-up to your question, Zolgensma is just now going into clinical trials for the intrathecal (IT) delivery for children and young adolescents, and depending how this clinical trial goes, they will start another clinical trial after that, and that will address the same issue regarding the IT delivery, but this will be for adults up to the age of 60 years old. All of this information regarding the last clinical trial is still tentative, because they will not know anything until the first IT clinical trial is completed.

Your child is still in the age range to possibly qualify for Zolgensma, but based on your healthcare system in Poland, this would be something that you would have to check with the health ministry for your child’s pediatric neurologist. I have quite a few subscribers and followers to my personal YouTube channel who live outside of the US, and I think a few of them even live in Poland. Each country bases their decisions on different criteria, so the only thing that we are allowed to tell you would be to please consult with your child’s pediatric neurologist and see if you can maybe find another doctor that has a better working knowledge of what SMA is and the treatments that are available.

Please do not quit the Spinraza treatments based on the fact that you would like to get your son on Zolgensma. Just because your son hasn’t seen too many benefits regarding Spinraza at the current time, like I said earlier, it may take a while for his body to start reacting to it. I would keep him on Spinraza as long as possible, until you are assured that he would be able to get Zolgensma. Alex, you and your family are in my prayers. Please keep us informed and let us know if we can help out in any other way.

[michael-morale]

Kristin – I wanted to address your comment and maybe answer the question that you had. AveXis is currently going through clinical trials of the IT or intrathecal delivery of Zolgensma. At the present time, Zolgensma is only available to infants and toddlers 2 years of age or younger, irregardless of the type of SMA that they have. (1, 2, 3 or 4) This treatment for these infants and toddlers is being done via an IV infusion. The reason why they are able to administer this treatment via the IV infusion, is that their bodies are so small, the treatment itself, doesn’t have any problem getting past the blood brain barrier and getting into their central nervous systems.

AveXis is working on the IT or intrathecal delivery because this is the only way they are going to be able to administer this treatment to older children, teenagers and adults. They have to do it intrathecally for older children, teenagers and adults, because if they were to try to do it intravenously, they would not only have to push an exorbitant amount of drug through our bodies, it would probably not get past the blood brain barrier to get into the central nervous system.

I’ve heard through the grapevine that AveXis is getting some good results so far in their clinical trials of the IT or intrathecal delivery method, and I truly believe that it will be available to those of us that are older. It may not be until the end of this year or maybe even the first part or middle part of 2020, but AveXis’ goal is to try to have this available to us as soon as possible.

There is also a lot of work going on with another treatment called Risdiplam, and there is also a combination therapy animal study with regards to Cytokinetic’s Reldesemtiv and Biogen’s Spinraza. Reldesemtiv will work along the same lines as Risdiplam, but it will be in combination with Spinraza, and so far, in these animal trials, Cytokinetics and Biogen are reporting some pretty impressive results.

All of these treatment options that are currently undergoing clinical trials and animal testing will be on our radar for discussion as soon as we know more information.

I apologize for such a lengthy response, but I wanted to give you my opinions. Have a great day.

[michael-morale]

I think it’s a little premature to say that Zolgensma is going to be the superior treatment. While Zolgensma is designed to replace the SMN1 gene, and Spinraza is designed to correct the SMN2 gene, both treatment options have their advantages. At the current time, AveXis is going through clinical trials with an IT or intrathecal delivery for Zolgensma so that it can become available to an older population, and while they are still going through clinical trials, I do have a gut feeling that it will become available sometime during the first part or middle part of 2020. Spinraza for me, has halted the progress of my disease, and I have seen a few benefits with regards to core strength and breathing. If anything, Spinraza has bought me more time until something else becomes available, like Zolgensma, Risdiplam, or maybe even the combination therapy between Cytokinetic’s Reldesemtiv and Biogen’s Spinraza.

One thing that we need to remember is that Zolgensma does not repair the damage that has already been done in our bodies. It will probably show good benefits for those of us that are older, but nothing has been developed as of yet that will repair damage that has already taken place.

[michael-morale]

Daria – I know that there had been a few cases where some individuals have taken both Spinraza and Zolgensma, but I think these were just test cases during some of the clinical trials. I believe they were testing whether or not these 2 treatments would be able to work together, since Spinraza is a cellular-based therapy and Zolgensma is a gene-based therapy. It’s probably unlikely that there will be a combination treatment between these 2 drugs, but I guess that is still yet to be determined by researchers and medical professionals. You actually ask a very good question, and I believe this is a question that quite a few people have had. I used to teach college for 18 years, and I used to tell my students that the only stupid question is the one that’s not asked, so thank you for your question.

I know that there is a treatment coming out maybe by the end of this year or sometime in 2020, and it’s called Risdiplam. I’ve also heard quite a bit of chatter that Risdiplam will work on the SMN2 gene, similar to how Spinraza works. I believe they are looking at the possibility of a combination between Risdiplam and Spinraza, but again, this is still in the clinical trial stage. We at SMA News Today will be giving our members more information regarding Risdiplam in the coming weeks and months, so be sure to keep checking in for this information.

If you have any further questions, please feel free to let us know. Thanks again for your question have a great day.

[michael-morale]

Lupa,

I can understand your confusion. As of right now, the only thing that I know that they are allowed to say regarding ZOLGENSMA, and by them, I’m speaking about AveXis, is that only infants were the ones there were in the preclinical trials. With regards to Type 2 and Type 3 SMA, not really a lot of information has been given. And to be honest with you, until ZOLGENSMA gets approved by the FDA, AveXis will probably not give out any information regarding the effects of this potential treatment outside of their initial Type 1 scope.

[michael-morale]

Yeah, even the doctor was somewhat surprised at my PFT results. I really think physical therapy has a lot to do with my improvements, because by increasing my core strength, I believe this has definitely helped with my breathing.

[michael-morale]

Thank you DeAnn. It’s a lot of work, but it’s well worth it.

[michael-morale]

When I started reading this post, I thought to myself, that question looks familiar. Welcome, and thank you for joining the SMA News Today forum. I’m glad that you took my advice and created an ID and became a member, thank you. Like Kevin and DeAnn said, there’s really not a lot of information out there regarding SMA Type IV. I met one individual with Type IV at the 2018 Annual Cure SMA Conference in September 2018. Out of all of the people that I met during this conference, they were the only one who had Type IV SMA.

Surprisingly, there’s even an SMA Type 0, which very few people know of. To be honest with you, I don’t think there’s any information on the Internet regarding this category of SMA. Let me do some research on it during the next week, and I’ll try to get you some more information. Kevin said to talk to your neurologist, which will probably be your best bet, but then again, some neurologists don’t even know what SMA is, which kinda scares me.

[michael-morale]

This is such an interesting topic Brianna. I use Dragon Speak to dictate on my computer while I’m home, and I ended up getting the Dragon Professional Individual version. The older versions had some quirks, but the Professional Individual version works really well.

I’m sure that there is a way to attach a microphone to a speaker that can be attached to your chair. I would call your local dealer that does work on your wheelchair to ask them if they have anything, or if they have any ideas on where you could go to get this. A lot of people with SMA have difficulty projecting their voice, so this may be something that could be very helpful to many people. I’ll call the company that I go through on Monday and see if they have anything, and I will let you know.

[michael-morale]

Hey Jennifer, welcome to the forum. You will find a lot of great people here, and if you have a question, please feel free to ask. It’s nice to have a place where we all know what each of us are going through, and there is no judgment past in this group of people. If you have a question, make sure that you ask, because if you have a question, trust me, there will be others that have the same question.

[michael-morale]

While I never really had a problem with my weight, I will say that since I have been on Spinraza for nearly 2 years, my diet has changed. My physical therapist put me on a high-protein diet when I started working out, and this is definitely helped with regards to my energy level and the way that I feel. I’m trying to consume more calories, but I’m trying to get good calories versus empty ones. I’ve never been a big sweet either, so desserts were never my problem.

When I was in junior high, about a year before I had my surgery for scoliosis, I did gain a little bit too much weight, but the summer before my freshman year in high school, I did a lot of swimming and lost the weight. Since then, I pretty much maintained my weight, but I still have to be mindful about how much I eat and what I eat.