New Infusion Rates ~ New Horizons ~ New Hope

I’m sitting in the infusion center – The Ambulatory Treatment Center (ATC) – at Sierra Nevada Memorial Hospital receiving my 21st infusion of Nexviazyme and my 258th enzyme replacement therapy (ERT). Today also marks the completion of my 10th year of ERT. It was May of 2012 when, after living 26 years with a diagnosis of some non-specific variant of Muscular Dystrophy, we learned that I didn’t, in fact, have MD. Rather, I had been living with a rare neuromuscular disease called Late Onset Pompe Disease … also known as Glycogen Storage Disease Type II … also known as Acid Maltase Deficiency. For a condition that virtually no one had heard of, it sure had a lot of names. The months between May and September 2012 were spent locating an infusion center that would administer enzyme replacement therapy, getting insurance authorizations, and trying to wrap my head around the fact that my life was about to change dramatically.

The process that led me to this new diagnosis was set in motion by the latest wave of muscular decline I’d been experiencing over the preceding year or two. I was going down fast. The discovery that I had Pompe Disease and the commencement of enzyme replacement therapy (initially with Lumizyme) saved my life. And I don’t use the phrase metaphorically. Had we not learned about Pompe Disease and started ERT, I’m quite confident I wouldn’t be alive today.

I won’t reiterate the long complicated and confusing path to diagnosis here. I’ve laid a lot of that out in other parts of the site. If you’re just tuning in and are interested in the background, feel free to catch up by clicking HERE.

Since transitioning from Lumizyme to Nexviazyme last November, I’ve had quarterly meetings with my Pompe Disease specialist at the University of California Davis Medical Center (UCDMC) in Sacramento. Last week, on August 9th, we had our most recent check-in.

My Nexviazyme infusions started with the same rates I’d been using with Lumizyme for the preceding nine years. For the medical dweebs out there … or for fellow Pompe patients who pay attention to details like infusion rates … that rate structure was as follows:

  • 30 mL/hr x 15 minutes
  • 90 mL/hr x 15 minutes
  • 150 mL/hr x 15 minutes
  • 210 mL/hr for remainder 

In early April, after receiving 10 Nexviazyme infusions, and after having no adverse effects from the new medication, we increased my infusion rates to the following, with the intention to revisit in another 3 months.

  • 50 mL/hr x 15 minutes
  • 100 mL/hr x 15 minutes
  • 175 mL/hr x 15 minutes
  • 225 mL/hr for remainder 

As with our visit in April, our intention for our latest visit, assuming that I’d still had no adverse reactions, was to make another rate adjustment. My doctor’s long-term intention is to start my infusions at my maximum rate and administer my entire infusion at a single rate. If/When we achieve that goal, we will have reduced the overall time of my infusions from about 4.5 hours to about 2 hours.

Today, we’re implementing the next step in this transition. Beginning today, my infusion rates are as follows:

  • 100 mL/hr x 15 minutes
  • 175 mL/hr x 15 minutes
  • 225 mL/hr for remainder 

We’re eliminating the initial 15-minute rate of 50 mL/hour and starting at 100 mL/hour. We expect this change to reduce my current infusion time by about 15 minutes.

Also, since making the transition from Lumizyme to Nexviazyme, my Pompe specialist has asked that I remain at the infusion center for an hour-long observation period after each infusion. This is out of an abundance of caution to insure that I don’t have a reaction to the medication. Since I’ve now completed nine months of Nexviazyme treatments without incident, my observation periods will be eliminated entirely after four more infusions at these new rates.

We’ll meet again in November and, assuming all continues to go well, we’ll take the next step towards one consistent rate for my entire infusion.

But there was even better news to come from my recent visit with my Pompe doctor!

At our visit, my doctor asked if I was familiar with the FORTIS study currently underway by the Astellas company (formerly Audentes).

I’ve been a patient speaker for Sanofi-Genzyme for years. A few years ago, based on a referral from the United Pompe Foundation, I was approached by Audentes and invited to speak with their team about my experience living with Late Onset Pompe Disease. My sister and I made a trip to San Francisco just before Thanksgiving 2018 and spent a wonderful day with the Audentes team. It was there that I learned about the research they were doing on the next-generation treatment for Pompe Disease – Gene Therapy.

Gene Therapy, if and when it is approved, would involve a single infusion to Pompe patients. The infusion would introduce a virus to the patient’s system that has had it’s genetic code removed and replaced with a healthy genetic vector that would spread, like a virus, through the Pompe patient. In essence, as the virus spreads, it introduces the new healthy genetic vector to the patient, superseding the mutated genetic code and causing the body to begin to produce the deficient GAA enzyme. It is the deficiency of the GAA enzyme that produces Pompe Disease. Pompe patients receive enzyme infusions, usually every two weeks, to supplement our bodies with the deficient GAA enzyme. As I mentioned at the top of this entry, today marks the 258th enzyme infusion that I’ve received over these past ten years. If Gene Therapy is successful, Pompe patients would theoretically receive one corrective infusion that would trigger our bodies to begin producing the GAA enzyme on our own. If effective, we would no longer require supplemental enzyme replacement therapy!

In the time since meeting the Audentes Team in 2018, I’ve been invited to meet with their team a few more times – virtually during the Coronavirus Pandemic. Over that time, Audentes has become Astellas and has launched the FORTIS study – the Phase I clinical trial for Gene Therapy. In fact, a couple of months ago, I was invited to work with Astellas to produce a video greeting to be played at the grand opening of their North Carolina-based facility that will be producing the forthcoming Gene Therapy infusions.

So yes. When my Pompe doctor asked if I was familiar with the FORTIS study, I told her I was very familiar with Gene Therapy, with the Phase I clinical trial, and with Astellas, who is sponsoring the study.

My Pompe doctor told me that she feels I’m an ideal candidate for the Phase II FORTIS study and asked if I’d be interested in connecting with the team running Phase I. Naturally, I was thrilled and gave an emphatic YES!

There are a lot of unknowns between here and there. The Phase I trials end in December of this year. We don’t know how long it will be between Phase I and Phase II. We don’t know if I’d be accepted into the Phase II trials. But having my doctor say that I’m “an ideal candidate” for this ground-breaking treatment is pretty exciting!

But on this day, as I mark the end of my tenth year of enzyme infusions … as I reflect on ten years of life that I’m quite certain I wouldn’t otherwise have had … as I experience a positive adjustment in my infusion rates on the newest FDA-approved treatment for Pompe Disease – Nexviazyme … and as I consider the exciting possibilities ahead of me with the forthcoming Gene Therapy treatments … I can’t help but be filled with wonder and hope.

Ten years ago, when I was diagnosed with Pompe Disease, there was only one treatment available in the US and it had just been FDA-approved in the preceding few years. Now, ten years later, there are two approved enzyme replacement therapies with a very promising third treatment in the pipeline. And Gene Therapy, which seemed like science fiction ten years ago, is now in clinical trials and on track to be a viable life-changing treatment for Pompe patients in the very near future. And miraculously, the prospects to access these exciting innovations keep showing up on my doorstep!

Those of us who live with Pompe Disease use the word “HOPE” a lot. For a community that lives with a very challenging condition … and that has witnessed many of our Pompe Family falter and perish to the ravages of this disease … we are a remarkably positive and hopeful Tribe. We live in hope that we will see a better day. We live in hope for our fellow Pompe Warriors who we know and love. We live in hope that science will continue to make advancements to improve our chances of survival. We live in hope that newborn babies diagnosed with Pompe Disease will have effective options to prevent them from having to live with the physical challenges and decline that those before them have faced. Most of all, though, we live with the hope that a cure for this unkind disease is on our horizon.

This past year has shown me that our hopes are not in vain. All of these things are happening. The future for Pompe patients is more hopeful than ever.

As always, thanks for following along with one Pompe Warrior’s journey. Feel free to leave comments or questions. Sharing my story has been a way to turn a pretty rough road into something positive.

Let Hope Flow!

~ Brian

“Fringe Benefits”

~ Brian Terhorst ~ 25 July 2022 ~

I spent the day at the infusion center today – The Ambulatory Treatment Center (ATC) at Sierra Nevada Memorial Hospital – as I do every other Monday. There, I receive life-extending enzyme infusions as a treatment for Late Onset Pompe Disease. Over the past six years, I’ve gotten to know the staff there as if we were all family.

The first few years of infusions there coincided with my last few years with my Canine Companion, PLAYA. They treated her like royalty there. And when PLAYA retired and I showed up with my successor Service Dog, COPPOLA, he inherited that tradition. The ATC crew sets up a warm blanket and a water bowl for COPI every time we visit.

Well, today, I arrived and got settled in. And COPI got curled up on his warm blanket. Just behind me, on the other side of a curtain, a young boy was having a really rough time receiving his treatment. I couldn’t see him but I could hear him. He was terrified. The infusion nurses were doing their best to calm him down and to assure him that it was all going to be okay. As they started his IV, I could hear this little guy’s anguish and fear as he cried and told the nurse that he didn’t like the way it felt.

The admissions nurse, Leslie, a person who I’ve known from my very first visit at the ATC, quietly came around the corner to where I was getting set up for my own four-hour infusion. Whenever I arrive at the center, Leslie always greets me warmly and asks how “my wingman” is doing – that being COPI. This morning, she came up to me and asked if she could borrow COPI for a few minutes. We got him leashed up again and she disappeared around the corner with COPI in his flashy blue Canine Companions vest.

Through the curtain beside me, I heard the little boy’s weeping come to an abrupt stop as Leslie introduced him to COPI. She explained that COPI is a working dog who visits the center every so often but that this was a special day because he got to visit with this little boy. The little guy immediately began to tell Leslie about his dog at home. They then compared notes on how much COPI wags his tail and how soft his fur is. The boy said that COPI seemed really happy and that he (the boy) thought COPI liked him (of course he did!). COPES stayed on the other side of the curtain for about twenty minutes until I heard them wrapping up the boy’s procedure. No more crying … just talk about dogs.

A few minutes later, Leslie brought COPI back to our spot where he curled up again on his blanket. Leslie pulled out her cellphone and showed me a photo of the little boy with his arms wrapped fully around COPI’s neck. COPI was the hero of the day today.

Even after all of these years as the handler of a Canine Companions Service Dog … I’m now with my second … I still marvel at their kind demeanor, their joyful willingness to perform their commands, their ability to help those of us with disabilities live an independent life, and just the deep friendship I’ve shared with both of my companions … but especially with COPI. Every now and then, though, things align in such a way that I’m reminded how the magic that lives under his soft black coat can easily transfer to another human being in need … well, in need of a hug.

A little while later, Leslie walked past me and thanked me for letting them share COPI with this brave little boy. I couldn’t help but thank HER. A beautiful thing happened today.

NOW! Streaming and On-Demand Downloads of Harmony Ridge!

This month marks the 30-year anniversary of the debut of Harmony Ridge on Community Radio KVMR-FM, Nevada City!

To mark the occasion, the latest edition of Harmony Ridge is now available as an mp3 stream or download from our Audio Library. Just open the “Radio” menu and select “Audio Library” or click HERE.

I’d love to know what you think. Feel free to share comments or suggestions by email at harmonyridge@kvmr.org!

Thanks for listening!

~ Brian

On-Demand Recordings of Harmony Ridge Coming on 22 June 2022!

COMING SOON!!! – Harmony Ridge will soon be posting on-demand mp3 recordings of our most recent programs! Beginning with our program of 22 June 2022, you’ll be able to listen to the current edition of Harmony Ridge by clicking HERE or visiting the “Audio Library” tab in the “Radio” menu!

Due to copyright and royalty restrictions, music programs cannot be publicly posted for longer than two weeks. Program links will expire after two weeks.

KVMR’s music programs are also available on-demand in the station’s audio archive for thirteen days following original broadcast. To access KVMR’s audio archive, click HERE.

Tests, Results, Adjustments and Lessons in Self-Advocacy

Good Day, Friends

Much has happened in the past month.

I’ve held off on posting an update because I’ve been waiting to see how things resolved. I make this blog post today in a very encouraged state. Things are going decidedly well.

First, let’s discuss my visit to the University of California Davis Medical Center (UCDMC) on 3 March 2022.

My Pompe specialist had made arrangements for me to visit the department of Physical Medicine & Rehabilitation (PM&R) to get comprehensive muscle strength tests and pulmonary function tests (PFTs). The intention was to get solid new baseline measurements for body strength and respiratory strength as I was starting Nexviazyme, the new enzyme replacement therapy I began receiving on 15 November 2021.

As a bit of background, I established a relationship with my first Pompe Disease specialist, Dr. Jay Han, at PM&R in 2012 right after my diagnosis. I had an exceptional relationship with Jay. He had a way of explaining very complex medical processes in terms that anyone could understand. More than that, though, he had a very positive outlook on life and a great sense of humor. He was treating eight or nine other Pompe patients at UCDMC but took great interest in my case. I signed on to some of his research studies and we worked very closely together. We got along wonderfully. I became a patient speaker for Sanofi-Genzyme (then, just Genzyme) and Jay and I took our show on the road. We would do co-presentations to physicians just learning about Pompe Disease; Jay would give the medical/technical details and then I’d talk about how those medical implications played out over the long life of a Pompe patient.

A few years later, Jay got an offer for a great job in Southern California and, disappointedly, I bade him farewell.

Another physician took Jay’s place at PM&R. Jay was a tough act to follow but I made the best of things. His replacement (whose name I won’t share here) was only basically familiar with Pompe Disease but, by that point, largely as a result of my collaborative projects with Jay Han, I had become somewhat of a patient expert on Pompe. I’ve always taken a very hands-on approach in my own medical care and am quite comfortable leading medical experts in my care. This was very much the dynamic I established with Jay Han’s successor at PM&R.

Around the time of my seventh year of Lumizyme infusions, I recognized that the stability I’d been experiencing since starting that enzyme replacement therapy in 2012, my muscle weakness was slowly creeping back in. I was seeing my Pompe specialist every six months and immediately brought to her my concerns that I was getting weaker again. Initially, she seemed to share my concern and agreed to investigate things further. But she never did.

Over the next year and a half, as my returning muscle weakness became increasingly more pronounced, I became more alarmed and more emphatic with my doctor to investigate remedies. While she continued to assure me that she would help explore adjustments, she did absolutely nothing. My repeated attempts to reach her by phone and through the UCDMC online portal went unanswered.

In the meantime, I began to educate myself. I maintain a fairly robust network of fellow Pompe patients around the world. As I’ve mentioned elsewhere, we Pompe Folk feel a great kindred spirit. Most of us keep ourselves very well informed on Pompe Disease and readily share information through a variety on online platforms. I learned from Pompe friends that it is not uncommon for people who have been receiving Lumizyme for six, seven, eight years (so-called “long haulers”), to eventually begin to plateau on the beneficial results of that treatment. This discovery led me to reach out to Dr. Priya Kishnani at Duke University, arguably the leading most authority on Pompe Disease in the world and certainly in the U.S.

Dr. Kishnani responded to my inquiry immediately and confirmed what I had heard from my Pompe network – that longtime Lumizyme recipients often can plateau on that drug. Dr. Kishnani informed me that there are a variety of approaches that can address this plateau effect, mostly involving increases in the amount or frequency of Lumizyme infusions. Dr. Kishnani’s staff generously provided me with their recently published medical reports documenting the plateau effect and outlining effective adjustments to respond to concerns over returning muscle weakness.

I promptly wrote to my Pompe specialist at UCDMC PM&R and sent her the medical report I had received from Dr. Kishnani’s staff. Much to my surprise, I heard right back from my doctor assuring me that she would read the report over the weekend and get back to me. Then, not so surprisingly, I heard nothing. Again, I made numerous attempts to reach my doctor by phone, email, and through the online portal. Nothing.

I’d had enough. I reached out to my representatives at Sanofi-Genzyme. I had already expressed my concerns to them. They confirmed their familiarity with patients who plateaued on Lumizyme. I reported to them my ongoing repeated efforts to get some movement from my Pompe specialist and her absolute unwillingness to address my concerns. My reps at Sanofi-Genzyme agreed to advocate for me. After getting no responses from my Pompe specialist, my reps agreed to help me find a more engaged physician. In fairly short order, they got back to me and connected me with Dr. Madelena Martin in the genetics department at UCDMC – The MIND Institute – and her exceptional Genetic Counselor assistant, Ayaka Suzuki. Dr. Martin and Ayaka became my Pompe specialists, and I effectively severed my former doctor from my care.

In my first couple of visits with Dr. Martin and Ayaka, we charted a course for the transition from Lumizyme to what we now know as Nexviazyme, as soon as the new drug received FDA approval. As I’ve documented elsewhere in my postings, Nexviazyme was ultimately approved by the FDA in August 2021, and I received my first infusion on 15 November 2021.

Because the doctors at the department of PM&R are better versed in prescribing durable medical equipment (e.g., wheelchairs, shower & commode benches, transfer devices, etc.), Dr. Martin recommended that I maintain a relationship with my former Pompe specialist at PM&R. While I wasn’t thrilled with the notion, I agreed to follow Dr. Martin’s recommendation. I reasoned that, if the PM&R doctor remained unresponsive, I’d have an effective advocate within the structure of UCDMC (i.e., Dr. Martin) to intervene.

I continued to meet periodically with the doctor at PM&R, specifically to address my medical equipment needs.

Now, fast forward to 3 March 2022. Dr. Martin and Ayaka had reached out to my former Pompe specialist in PM&R and had made arrangements for me to get comprehensive muscle testing and pulmonary function tests on March 3rd. With their assurance that we’d get these new baseline measures to inform my responses to Nexviazyme, I made the hourlong drive from Grass Valley to Sacramento for my first in-person visit at UCDMC in almost two years (due to Covid). I was also slated to get updated blood panels and Hex4 urine tests that day, which I completed before reporting for my appointment at PM&R.

When I arrived at my appointment, I told the intake nurse that I was scheduled to get the strength tests and PFTs done that day … and that I also needed them to record my body weight to confirm that the dosage of Nexviazyme that I was receiving was accurate. I was stunned to learn from the intake nurse that both of the two specialists who were to conduct the tests that brought me all the way down to Sacramento – in the midst of Covid – were on scheduled vacations and that I’d be unable to get the tests completed. The nurse also told me that the doctor was running late and that I’d have a bit of a wait. This doctor, who had been stonewalling me for over two years while my condition continued to worsen, had assured my new Pompe specialist that my tests would be completed on this day, and hadn’t even checked to confirm that the people who would perform those tests would even be there. Suffice it to say that I was furious and disgusted.

I told the intake nurse that I’d like to have my weight taken and that I’d be leaving. I told her that I had no interest in meeting with the PM&R doctor. The nurse told me that she’d report to the doctor and get right back to me.

Miraculously, the PM&R doctor rushed into the room within minutes and assured me that “we’d get those tests done today … for sure.” Pathetically, she had the intake nurse conduct my pulmonary function tests, something she had never done before. I then learned that someone had recalibrated all of their equipment and the results of the tests were unreliable. Then, she had their Traumatic Brain Injury specialist conduct my strength tests. The TBI specialist was a very kind person but admitted to me that she had never performed strength tests. So, basically, the results of these tests that the PM&R doctor had hurriedly cobbled together, were unreliable. I wanted nothing more than to get out of there.

Before I left, I asked if they could please capture my body weight, a process that requires hoisting me into a lift equipped with a scale. I’m unable to stand so I can’t just step onto a scale. Historically, we’ve known the exact weight of my wheelchair so I could alternatively drive onto their large scale, and we could subtract the known weight of my wheelchair. But in the two years since my last in-person visit to PM&R, I got a new wheelchair, and we didn’t yet have the tare weight. So, they deployed two medical assistants to get me into the lift. They helped me into their harness and began to lift me out of my chair. As soon as I had cleared the seat of my wheelchair, their lift froze. The assistants left me hanging, partially suspended, in the hallway and went to find someone to help. Some ten minutes later, a nurse returned and inspected the lift. She told me that the lift hadn’t been charged and that they wouldn’t be able to record my weight. She was able to lower the harness back into my wheelchair and I was able to escape.

As I was pulling away, the nurse instructed me to stop at the reception desk to schedule my next appointment in six months. I dashed out the door, past the reception desk, and swore to myself that I would never … ever … subject myself to another appointment with that PM&R doctor.

When I returned home, I emailed Dr. Martin and Ayaka and reported that their efforts to arrange those two crucial tests were in vain. I reported that the PM&R crew was also unable to capture my body weight and that this entire trip was a fiasco and a complete waste of time. I was able to report that I’d successfully gotten my blood panel and Hex4 urine test. Finally, I reported that I refused to ever see that doctor again. I had already terminated her as my Pompe specialist and was now terminating her as my physical medicine specialist. I asked that, if Dr. Martin wished me to maintain a relationship with PM&R, I wanted a referral to another doctor.

I’m happy to report that Dr. Martin and Ayaka have since established a relationship with a new doctor in PM&R and I’ll have my first appointment with her on 28 April. During that visit, we will officially conduct the two studies that were supposedly done on 3 March.

Meanwhile, the results of the blood panel and Hex4 urine tests that I had done on March 3rd have come back. And the reports confirm what my body already knows … that Nexviazyme is working much better than Lumizyme!

  • The blood test was to measure IgG for Nexviazyme. This is an antibody test. When a foreign substance is introduced, our bodies are adapted to identify and resist potentially harmful elements. Our bodies will develop an antibiotic response. The IgG test measured if my body was having an antibiotic reaction to Nexviazyme. If the test determined that I was having a mild reaction, this would be expected and would not be of concern. If the test determined that I was having a serious antibiotic reaction to the new drug, this wouldn’t necessarily have been of concern, however, it would suggest that my body was not fully assimilating the beneficial results of Nexviazyme. The IgG antibiotic test for Nexviazyme came back negative. My body is not presenting any measurable resistance to the new medication! This means that I’m fully assimilating the new treatment!
  • The Hex4 urine test measures the degree to which our bodies are clearing glycogen. Pompe Disease is also known as Glycogen Storage Disease Type II. This disease is the result of an enzyme deficiency (an enzyme called Acid Alfa Glucosidase [a.k.a. “GAA”]). The GAA enzyme plays a key role in converting glycogen – a natural sugar, ingested from the foods we eat – to glucose, the form of sugar our body uses to build muscle and create energy. Without adequate quantities of the GAA enzyme, our bodies accumulate toxic levels of unconverted glycogen. The result is permanent muscle cell damage, muscle weakness, and fatigue. Over time, if not treated, this can result in permanent muscle loss and death. The Hex4 urine test measures the degree to which our bodies are expelling glycogen in our urine. There isn’t a set standard for a healthy measurement of expelled glycogen in urine. The test has to be taken periodically and compared, over time, to other measurements. I had a Hex4 urine test right before I received my first Nexviazyme infusion in November. On March 3rd, after three months of Nexviazyme infusions, my Hex4 urine test indicated that my body is expelling a considerably higher volume of glycogen! More glycogen out means less glycogen being stored in my muscle tissue and less potential for further damage!

The results of these two tests support what I have already been feeling in my body. As reported in earlier entries, I’ve noticed a slight improvement in my breathing strength. Again, I’m ventilator dependent 24/7. This is the result of progressive serious muscle wasting in my diaphragm. My lungs are relatively healthy. But because my diaphragm muscles have become so compromised, they’re just not strong enough to pump my lungs. But in the normal course of my daily routines, there are times when I have to remove my ventilator for dressing, showering, etc. Around the time of my sixth Nexviazyme infusion, I noticed that, when I had my ventilator off, I was able to breathe more easily and was less panicked to get back on air support. Since that time, I haven’t noticed additional improvement, but I have noticed that the gains I experienced around Nexviazyme Infusion #6 have been sustained.

I’ve also noticed both improved energy immediately following my infusions as well as better energy and stamina in the days following my infusions. My mental acuity feels improved, I have better sustained energy through the day, and I’m sleeping better.

My verbal reports to Dr. Martin combined with the positive results of the recent blood and urine tests, as well as my tolerance of Nexviazyme with no adverse fluctuations in my vital signs during infusions (i.e., blood pressure, body temperature, and oxygen levels), have caused Dr. Martin to prescribe an adjustment in my infusion rates.

Today is Nexviazyme Infusion #11. And as of today, my infusion rates have been adjusted to the following protocol.

  • 50 mL/hr x 15 minutes
  • 100 mL/hr x 15 minutes
  • 175 mL/hr x 15 minutes
  • 225 mL/hr for remainder 

This infusion rate increase is expected to reduce my overall infusion time by about 30 minutes and represents rates well beyond those we used for my Lumizyme infusions. As I complete this lengthy entry, I’m about 2/3 through my infusion with no signs of complications.

And so, to tie a bow on this report for today …

We, the Warriors of the Pompe Tribe, are living with a rare disease that is still relatively unknown, even among the medical community. It is incumbent upon each of us to learn how to manage our disease because, at least at this time, we can’t really expect our physicians to fully understand Pompe Disease or our unique experiences living with it. We deserve the best care available. To ensure that we receive that care, we must insist on having competent, well-informed, fully engaged, and collaborative professionals on our team. The failure of any member of our team to meet these standards can have potentially grave consequences and that person needs to be replaced by someone who does. I’ve been fortunate to work with an exemplary crew of experts who have kept me healthy and alive. It’s been very rare for someone not to live up to the standards we deserve … but there have been a few. This past month, I’ve had to release from my team a person who has twice let me down. I feel empowered having taken charge of this situation.

And finally, Nexviazyme is working much better for me than Lumizyme was after nine years using the latter treatment. I feel the improvements in my body and I’m seeing the improvements in my lab results.

If you’re a patient living with Pompe Disease, ask your specialist if Nexviazyme could be a good choice for you. Thus far, it clearly is for me!

Thanks for following along!

In Spirit,

Brian

First Pompe Check-In Since Switching to Nexviazyme

Hello, there

On February 8th, the day following my seventh Nexviazyme infusion, I met with my Pompe specialist for the first time since switching from Lumizyme (after completing nine years on that medication) to Nexviazyme.

If you’re just checking in on this blog for the first time, I reported some exciting news that arose around the time of my sixth Nexviazyme infusion. I’ve been dependent on a non-invasive ventilator 24/7 for about six or seven years. Pompe Disease has so weakened my diaphragm muscles that I’m just barely able to breathe on my own. I began using a bipap machine at night in 1996 following a two-week stay, intubated, in the intensive care unit. I had developed a severe pneumonia that nearly claimed my life. Once my lungs had cleared enough to take me off the breathing tube, we learned that, when I fell asleep, I would stop breathing. I acquired my first bipap machine at that time. It would be sixteen more years before we’d learn that I had Pompe Disease and that diaphragm weakness and ventilation were kinda par for the course. By the time of my Pompe diagnosis in 2012, my diaphragm was pretty well shot, and it wasn’t much longer before I needed breath support during the day. So, around 2014-2015, I had switched over to a non-invasive ventilator that I could tote around on my wheelchair. By that time, my forced vital capacity (i.e., breathing strength) was measured at 23% of normal. It’s a wonder I lasted that long without 24/7 assistance!

During the normal activities of my days, there are times when I need to remove my ventilator – when I’m showering, dressing, brushing my teeth, or transitioning from my daytime vent to my nighttime vent at bedtime. For the past many years, I’ve only been off my ventilator for a couple of minutes before I get panicked and grasp for my ventilator hose to catch my breath.

Well, around the time of my sixth Nexviazyme infusion, I discovered that my breathing strength was noticeably improving. When off my vent for a few minutes, I was able to sustain my breathing on my own. There were even times that I forgot to put my mask back on for minutes and minutes. Very unusual. The first few times this happened, I chalked it up to just having “a good day.” But after a sustained pattern of easier breathing that lasted days and then weeks, it became evident that something had changed. My morning care providers also noticed this change and commented that it looked like I was doing better. And I was. And I am!

I emailed my Pompe specialist and Genetic Counselor with this news when it developed. But our visit on February 8th was our first chance to discuss this exciting news and our first real face-to-face conversation (albeit online) since I switched from Lumizyme to Nexviazyme on November 15th.

We have communicated through email since making the switch … many times. There were a lot of hurdles involved in getting my Nexviazyme infusions started, mostly involving insurance approvals. These details are documented elsewhere in this blog. But there have also been some minor snags associated with the chain of authority among my Pompe specialist, my primary care physician, my infusion center pharmacy, and my infusion center staff. Again, those have been documented in other entries but suffice it to say that anytime even a minor tweak takes place in my weight, my infusion orders, or anything else, it triggers a complex chain of necessary approvals.

I communicate with a handful of fellow Pompe Disease patients who have also made the switch from Lumizyme to Nexviazyme. Almost all of those other folks pretty much jumped from one drug to the other without any major adjustments in the published standard of care. One or two were required to remain at their infusion centers following their first or second Nexviazyme infusion and then that requirement was dropped.

My Pompe specialist is being exceptionally cautious, relative those supervising other Pompe patients. We began my Nexviazyme infusions with half hour intervals between my initial three rate increases (as opposed to fifteen minutes. I was also required to stay at my infusion center for two-hour observation periods for my first few infusions. My specialist also required pre-medication of Solu Medrol prior to starting my infusions. Due to a miscommunication, that drug was placed in my crash cart in case of emergency rather than administered ahead of the infusion as a preemptive measure.

I asked my specialist during our visit why we were taking such a cautious approach when others have been up and running without such precautionary measures. My doctor explained to me that (1) mine is a very advanced case of Pompe Disease. If I develop an allergic reaction to this new drug, it’s possible that that reaction could also extend back to Lumizyme. If that were to happen, I’d be unable to receive my prescribed doses of either Lumizyme or Nexviazyme while we backtrack and try to slowly reintegrate one or the other of those drugs. If that were to happen, she explained, the losses I might experience from going without enzyme replacement therapy could be unpredictable at best and catastrophic at worst. My doctor also explained to me that (2) she has supervised enzyme replacement therapies for other patients with glycogen storage diseases where they have developed allergic responses after as much as a year of uneventful infusions. In some of those cases, she explained, she had to walk back infusions and basically start all over, rebuilding in baby steps. She explained that, once you’ve lost valuable ground like that, you learn to be very cautious. I couldn’t disagree with her approach.

After completing my first three Nexiazyme infusions with no adverse reactions, we reduced my observation period from two hours to one hour. We will continue with that practice until further notice.

After my sixth Nexviazyme infusion, we reduced the time interval between my first three rate increases from thirty minutes to fifteen minutes. This change cut about 25 minutes off of my infusion time, dropping it down to about three and a half hours.

During our February 8th conversation, we discussed continuing with this protocol through my tenth infusion (so two more after today). If all continues going well, my doctor will prescribe an entirely new rate structure for Nexviazyme. That change will reduce my overall infusion time by probably another half hour. If I successfully tolerate that change, she has plans for other rate changes with the ultimate goal of bringing my overall infusion time down to 2 to 2.5 hours! That’s an enticing incentive; historically, my infusion days have tended to run about five hours with check-in, setup, and check-out. To achieve this new goal, we will likely be retaining one-hour observation periods until we get there and maintain stability. But this is definitely something to look forward to.

In our conversation, we discovered that my doctor’s preferred administration of Solu Medrol BEFORE each infusion wasn’t taking place. (I hadn’t been aware that she wanted me to take this drug before my infusions.) But since I’ve successfully tolerated seven Nexviazyme infusions by this discovery, my doctor agreed that we don’t want to fix what seems to be working. So I will continue to receive my Nexviazyme infusions with my only pre-medication being a single 500mg Tylenol a half hour before we start.

I also have an appointment next week – March 3rd – for a visit to Sacramento to visit the University of California Davis Medical Center, Department of Physical Medicine & Rehabilitation. During this visit, I will receive comprehensive strength tests to establish new baseline measures. In the coming months, we will take other strength tests and measure them against these new baselines. I will also receive my first Pulmonary Function Tests (PFTs) to establish a new baseline for my breathing strength. Since I’ve been ventilated 24/7, we’ve stopped measuring my PFTs. But since it appears that my breathing in improving, we want to get a new baseline so we can objectively measure future scores against now. I will also get a new set of lab work done including my first HEX4 urine tests since starting Nexviazyme. The HEX4 urine test measures how the body is expelling glycogen. The symptoms of Pompe Disease are caused by the toxic accumulation of unconverted glycogen in our muscle tissues. We took this measure right before I started Nexviazyme. A new measure three months later will ideally show a similar or (preferably) better rate of glycogen expulsion.

So, the highlights of my first check-in since starting Nexviazyme:

  1. My breathing appears to be improving! On March 3rd, I’ll receive my first Pulmonary Function Tests in years to establish a new baseline. This will allow us to take future measurements against this baseline to determine objectively if my breathing strength is improving.
  2. I’m successfully tolerating Nexviazyme. My doctor is not going to recommend pre-medication except for Tylenol. We have reduced my observation period and will keep it at one hour while we continue to periodically adjust my infusion rates over the coming months. The next rate adjustment could come as early as my first infusion in April. If I continue to tolerate Nexviazyme without incident, our goal is to increase my rate structure until my overall infusions are completed in 2-2.5 hours!
  3. On March 3rd, we’ll get my first objective muscle strength tests in several years and establish a new baseline of arm, leg, neck, and trunk strength, against which future measurements will be taken.
  4. On March 3rd, we’ll get our first objective before-and-after measurement since starting Nexviazyme. The HEX4 urine test will provide a measurement of how much glycogen my body is expelling. This will be compared to the test I had taken just before making the switch.

This blog entry comes as I’m about halfway through my eighth Nexviazyme infusion; today marks my 245th enzyme replacement therapy infusion since starting them in September 2012.

I’m happy to be alive and optimistic about this unfolding next chapter in a life with Late Onset Pompe Disease!

Let Hope Flow!

~ Brian

Changes at Nexviazyme Infusion #6

Hi there,

Today, I’m receiving my sixth infusion of Nexviazyme. I haven’t made any blog posts since my second infusion in late November, shortly after the change from Lumizyme. There were definitely some fits and starts getting things going but everything has been smooth sailing since.

I’m making this entry because a couple of things have changed.

First, I’ve been in regular communication with my Pompe specialists since making the switch in medications. My doctors are prescribing a measured approach to this new medication relative to other Pompe patients. My regimen thus far has involved infusion rate increases every thirty minutes until I reach my max rate. With Lumizyme, those increases were implemented every fifteen minutes and, near as I can tell, most other Pompe patients are increasing their Nexviazyme rates at fifteen minute intervals. Also, my doctors initially required a two-hour observation period following my infusions to ensure that I don’t have an adverse reaction.

After my first three infusions without incident, my doctors agreed to reduce my observation period to one hour. We’re continuing with that practice for now.

But this week, my doctors have agreed to reduce the intervals between rate increases to fifteen minutes. So my infusions start at 30 mils per hour. Then, every fifteen minutes, we increase by 60 mils to a maximum rate of 210 mils. This will reduce my overall infusion time by over thirty minutes, which is fine by me.

The more exciting news, though, is that I’ve noticed a change in my breathing strength over the past two weeks!

If you’re dropping in on this blog without having read earlier entries or some of the background information I’ve provided, I’m dependent on a non-invasive ventilator 24/7. This has pretty much been the case for the past six or seven years. Even so, there are times when I have my vent off … when I’m showering, dressing, brushing my teeth, etc. Generally, after having my vent off for even a short while, I run short of breath and can even get a bit panicked because I’m having a hard time catching my breath.

In the normal ebb and flow of living with Pompe Disease, I have good days and bad days. Some days, I feel more energetic, and things seem easier. More often, though, there are days I just feel depleted, and things seem more labored, weak, and difficult. I’m used to those peaks and valleys and just kinda ride with them.

I’ve documented elsewhere in this blog that Nexviazyme infusions produce a dramatically different short-term reaction than Lumizyme did … at least for me. Lumizyme tended to put me in a very sedated state beginning about two hours into my four-hour infusions. That haze would last through most of the day following my infusion days. Nexviazyme, on the other hand, produces a subtle but distinct improvement in my energy and mental clarity that lasts well through the day following an infusion day. Over these past twelve weeks, I’ve noticed that my overall stamina lasts a little bit longer after each infusion.

The more exciting news, though, is that my breathing strength appears to be very gradually improving. Again, I’m accustomed to the normal to-and-fro of good days and bad days. But about ten days ago, I noticed that, when I had my vent off, it was easier to breathe on my own and I didn’t feel panicked after having it off for a few minutes. At first, I attributed this experience to just having an easier day. But after it happened several days in a row, it caught my attention. Now, almost two weeks later, there appears to be a discernible pattern. With slightly improved breathing, I’m also feeling more alert and upbeat.

For the past several years, my medical team has stopped conducting Pulmonary Function Tests (PFTs) mainly because I’m ventilated all the time. If I remove my ventilator and try to run through the regimen of PFTs, it’s a given that things are going to look strained. The last time I underwent PFTs, it was determined that my breathing strength was about 23% of normal.

I meet with my Pompe specialists in the next few weeks and I believe we’re going to get comprehensive muscle tests to establish a new baseline. I’m going to ask if we should get new PFT results, also to get a new baseline. If my breathing is, in fact, improving, we need to be able to measure against a reliable score.

In the moment, though, I’m elated! I wasn’t expecting any improvement from this new medication … and certainly not this quickly. The best expected results of Enzyme Replacement Therapy (ERT) are really stability. I was simply hoping to see my clear decline over these past few years level off. That I’m actually feeling better … for the first time in years … is truly something to celebrate!

I’ll keep you posted as things evolve. But the news is all good!

Thanks for following along.

~ Brian

Nexviazyme Infusion 2.0

Greetings!

Today, I’m settled in at the infusion center and am currently receiving my second dose of Nexviazyme. For details about how the first one went, feel free to browse my blog entries from two weeks ago.

In short, though, I had a very positive reaction to that first Nexviazyme infusion. Granted those are immediate reactions. The long-term efficacy of this new enzyme replacement therapy will be determined over time. After I started Lumizyme in September of 2012, it took a few months before I began to notice any differences. But having an immediate positive reaction after that first Nexviazyme infusion was certainly a nice “shot in the arm”!  :/ (… a little IV humor, there, folks!)

Since that first Nexviazyme infusion two weeks ago, I encountered another bureaucratic bump in the road. It was fortunately resolved right before the Thanksgiving holiday, but it came right down to the wire again.

Before we began this transition process, it had been quite awhile since I’d been weighed. And since the dose of my enzyme replacement therapy medications is based on my body weight, it was essential that we had an accurate weight. The last time I was accurately weighed – down in Sacramento at UC Davis Medical Center – was over eighteen months ago, at which time I weighed 250 lbs. The method we used for weighing me in Sacramento, since I’m unable to stand, was to maneuver my power wheelchair onto their flat scale and subtract the known weight of my chair (443 lbs.). Since that last weigh measurement, I’ve gotten a new wheelchair, so we hadn’t yet calculated its weight. I haven’t been down to Sacramento since then, where they have the gear to lift me out of my chair and weigh the chair. My local hospital doesn’t have such a scale.

At my local hospital, we tried a couple of different methods to get my weight. Over two weeks, we got two different weights, 30 lbs. apart. We realized that neither of those weights could be considered dependable. A week ago, my local hospital acquired a reliable scale, and I went in and got weighed – 238 lbs. (Kinda nice that in two years of Covid-induced isolation, I’ve actually LOST 12 lbs!). That’s the good news!

The bad news was that this new weight measurement required that my medical orders needed to be revised. This, in turn, set in motion another tedious chain of emails, faxes, and multiple parties (my Pompe Specialist, my Primary Care Physician, the Infusion Center staff, and the hospital pharmacy) to connect the dots, order my medication, and have everything in place for today’s infusion.

But as mentioned, it all came together late last Wednesday – the day before Thanksgiving. So here I am, receiving my second Nexviazyme infusion with the correct dose for my body weight.

There’s peace and harmony in the mountains! I’m about half way through this treatment now and my observation period has been reduced from two hours to one hour. So God willin’ and the creek don’t rise, I’ll be home while the sun is still shining.

# LetHopeFlow

~ Brian

Reflections – The Day After

Hi, All

Yesterday – 15 November 2021 – I received my first infusion of Nexviazyme – the recently-approved Enzyme Replacement Therapy (ERT) from Sanofi-Genzyme.

This followed nine years of Lumizyme infusions (also a product of Sanofi-Genzyme).

This milestone transition followed over two years of discussions, evaluations, research, negotiation, and a whole new battery of baseline studies in preparation to move on from Lumizyme. This long process included me abandoning my former Pompe specialist and finding a new one who would be more responsive to my changing condition and needs.

In late 2018 – early 2019, I began to plateau on the beneficial effects of Lumizyme, a fairly common experience among Pompe patients who have received that drug for seven or eight years. Together with my doctors, I considered increasing my Lumizyme dose, as many Pompe patients have done after plateauing. By the time we actually faced that decision, a new drug was already in clinical trials under the lab name, “Neo-GAA” – an acronym meaning “new GAA.” GAA is the abbreviation for the enzyme, acid alfa glucosidase, the deficiency of which causes Pompe Disease.

My new Pompe specialist informed me that she had experienced denials from insurance companies when she tried to adjust the Lumizyme dosage for other Pompe patients who had plateaued. Because higher doses of Lumizyme deviated from the prescribed standard of care, some insurance companies would not approve an alternate dose. Because Neo-GAA was nearing the end of its clinical trials, my doctor invited me to consider waiting for the new drug. She felt that, because my body was already not responding as favorably to Lumizyme as it once had, administering more was probably just delaying the inevitable. Because Neo-GAA was an entirely different composition, my doctor felt that my body would likely respond more favorably. So we decided to wait.

Neo-GAA was originally scheduled for FDA approval in May 2021. For unexplained reasons, the FDA decided to delay that decision by three months. In August 2021, the FDA approved Neo-GAA at which time it was assigned the new brand name, Nexviazyme (avalglucosidase alfa).

A month later, I met with my Pompe specialist, and she agreed to write the orders for the switch from Lumizyme to Nexviazyme. I began this blog at about that time to document this process. Readers can review the blog posts to see how that process unfolded. It took a while.

 But yesterday, the stars aligned, and I received my first Nexviazyme infusion.

Today, I want to share with you the noticeable differences between the way my body has historically reacted to Lumizyme and the way I’m responding to Nexviazyme.

Ever since my first Lumizyme infusion in 2012, I have had a consistent response to that drug. Lumizyme infusions took about four hours to administer. Beginning about an hour or two into the procedure, I would feel a gradual onset of fatigue. The physical fatigue was accompanied by a state of mental and emotional sensitivity. It’s difficult to think of a suitable comparison but I would become sensitive to light and sound. I would also find it difficult to reason clearly or make decisions. After my first few Lumizyme infusions, I would set the stage for my homecoming by having my dinner planned and prepared so I wouldn’t have to cook or decide what I was eating. It was also common for me to get home, turn down the lights and maybe light some candles, and put on soft music. I would avoid anything, like TV news, that would trigger anxiety. I would basically retreat from the outside world and, if possible, remain so for the day following my infusion. That heightened sensitivity would typically last a full 24 hours.

I have a few Pompe friends who made the switch from Lumizyme to Nexviazyme over the past few weeks and they have reported feeling energized after receiving their first Nexviazyme infusion. Some have speculated that this may be due, in part, to the fact that Nexviazyme is mixed with a dextrose solution (versus the saline solution used with Lumizyme). Dextrose is a sugar which would reasonably give patients a mild energy boost. One Pompe friend asked her doctor about this theory and her doctor said that dextrose wouldn’t really explain much of an energy boost. Whatever the case, I went into yesterday curious to see if I would have a similar reaction.

Yesterday was a very long day, relative to my normal patterns. I was up at 5:00am and went through my normal morning routine. Because I was expecting a long stay at the infusion center, my sister came by in the morning and picked up COPPOLA, my service dog, so he wouldn’t be confined all day. I left for the infusion center at 9:00am and stopped to get some lunch to bring with me. I arrived at the infusion center a little before 10:00am and my infusion was underway by 10:40am. The infusion ended at 3:00pm and I had to remain at the center for a two-hour observation period. I left at 5:00pm and was home by 5:15pm.

I was very tired … but not at all in the way I’m used to after a Lumizyme infusion. I was just tired from a long day. I put away all my gear, my sister dropped by to return COPI, and I settled in. After getting a drink and catching my breath, I began to notice a distinct difference – not just compared to a Lumizyme evening but to any other evening. My mental acuity was much sharper. After about an hour at home, I felt motivated to prepare dinner, sort through emails, return messages, and check in with my family. My energy wasn’t only up, I was feeling exhilarated and social – VERY different from a regular evening and certainly different from an evening following a Lumizyme infusion.

I slept great last night and today, that mental acuity and energy have been sustained.

One element that, for me, is consistent with both Lumizyme and Nexviazyme is my dream time afterwards. Following Lumizyme infusions, I would have super-vivid technicolor immersive dreams with epic storylines. When I woke during the night last night, I was delighted to find that Nexviazyme infusions are followed by similar dreams. Fortunately, I’m not a nightmare person. I have marvelous life-affirming dreams … where I’m not bound by the constraints of Pompe Disease. In my dreams, I can run and leap and fly. So being able to enjoy turbo-charged versions of dreams like that after infusions is a perk!

Enzyme Replacement Therapy (ERT) is not really about an immediate response. ERT nourishes the deficient system of a Pompe patient with normal levels of enzymes that enable our bodies to efficiently process glycogen. ERT is a long-term project. So ultimately, the efficacy of this new drug – Nexviazyme – will be revealed over months and years. But after nine years of feeling completely depleted after ERT, if this new treatment means I’m going to feel mentally and emotionally uplifted, I can get excited about that. I already am!

So, this story will unfold as it does. But after one Nexviazyme infusion, my report is that I feel great … better than I’ve felt in a long time. And since this blog is intended to inform fellow Pompe patients of what they might expect when facing the transition from Lumizyme to Nexviazyme, my report is decidedly favorable.

~ Brian