[6 min read]
In this article:
- A new drug recently approved by the FDA is a major advance in the treatment for a familial type of amyotrophic lateral sclerosis, or ALS.
- The new drug, marketed under the name Qualsody, treats ALS associated with the SOD1 gene by binding with messenger RNA and preventing expression of the disease in DNA.
- Swedish is the first hospital in Washington State to administer this new gene therapy to a patient with ALS.
Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease, is a progressive and degenerative disease that affects the motor neurons in the brain and spinal cord. It leads to muscle weakness; difficulty speaking, breathing, and swallowing; and ultimately death. It’s a devastating disease affecting thousands of people worldwide, with an estimated prevalence of 4-6 per 100,000 individuals.
For years, ALS patients have been treated with neuroprotective drugs to help delay disease progression. In late spring, the U.S. Food and Drug Administration (FDA) approved a groundbreaking new gene therapy for a heredity type of ALS caused by a mutation in a gene called SOD1. The SOD1 mutation accounts for some 20% of all familial ALS cases. An impactful new drug, marketed under the name Qalsody® (tofersen), has shown great promise to potentially protect more neurons from onset of disease. The drug and gene therapies like this are prospective game-changers for the treatment of familial forms of ALS.
In early December, Swedish became the first hospital in Washington State to administer the gene therapy, bringing new hope for patients with ALS and their families. Michael Elliott, M.D., Medical Director of Neurology at the Swedish Neuroscience Institute, helped lead the effort to bring tofersen to Swedish. We spoke with Dr. Elliott to learn more about the drug and what makes Swedish a standout in care and treatment for patients with ALS. (This interview has been edited for length and clarity.)
What are the types of ALS? How do they vary?
In about 90 percent of patients, we see what we call sporadic ALS, meaning there is no family history. In the other 10 percent of patients, we see a family history. When we do genetic testing, in the sporadic ALS patients, we’ll find a gene [mutation] in maybe five to 10 percent of those patients. When we do genetic testing on patients with a family history, we almost always find a gene. We think right now there are about 50 genes associated with ALS. The SOD1 gene was discovered in the 1990’s. When we look at it by itself, SOD1 is responsible for approximately 20 percent of familial ALS cases.
How do you determine what type of ALS a patient has?
When patients first present with ALS, it’s often not clear what's going on. On average it takes about a year from the time that a patient first gets symptoms to the time that they're diagnosed. Once a diagnosis is made and we confirm that a patient has ALS, we then do genetic testing. There are gene panels that we can send using a saliva sample. We can have a kit sent to a patient's home and they mail in [their saliva sample] and typically in two to four weeks we get a result back and know if they have a genetic mutation or not.
How does tofersen work?
The first thing to know is that this drug can’t help patients with sporadic ALS or who don’t have the type associated with the SOD1 gene. It's a very specific treatment called an antisense oligonucleotide, or ASO. What it does is a very specific strategy in gene therapy where a segment of this drug binds messenger RNA and prevents the production of a pathological protein, so you're basically blocking the expression of the disease in the DNA. We think because it's so targeted, it is potentially even more effective than [current] nonspecific therapies for ALS, which are broader neuroprotective drugs that help keep neurons alive longer in a disease state.
We are still understanding how effective it is. There’s a functional scale we use to measure disease progression. ALS patients often get weak in their extremities. They can also lose the ability to speak and swallow. Or they can have respiratory difficulties and difficulty with breathing. These are some of the functions we measure.
Though its effect on clinical measures we use in patients with ALS has been difficult to demonstrate in relatively short clinical trials, the FDA approved the drug because it had such a good effect on other biomarkers. We think if people can get the drug for longer it has the potential to modify the disease in a more significant way. We are still learning and there is a lot of experience being gained with this new approach.
Illustration of motor neuron degradation. ALS is a degenerative disease affecting motor neurons in the brain and spinal cord.
Can tofersen be used in combination with other therapies? Are there eligibility parameters?
Yes, it can be used in combination with other FDA-approved, disease-modifying therapies. Patients with SOD1 can take those neuroprotective drugs and the tofersen gene therapy.
It’s probably with adults where you'll see use of this particular drug as this disease is very uncommon in children and was not tested in younger patients. Guidance on who should receive this drug is still being worked out. Going forward we may be asking how advanced this patient is. Are they early in the course of their disease or are they really so advanced that perhaps too much has been lost to start this type of treatment? We don't really know the answer to where the line is at present.
How did Swedish become the first hospital in Washington State to offer this treatment to a patient?
It's currently being used across the country. In our ALS clinic, we probably follow about 200 patients, and we had no one who was SOD 1 positive. My understanding is that there were very few patients with this gene identified in the state. And then we had a hospitalized patient that one of my partners diagnosed with ALS. We did genetic testing and discovered that this patient had a mutation in the SOD1 gene. I spoke with the patient about this gene therapy and suggested that they should consider initiating this treatment.
So, it took a lot of effort. A lot of effort. I can't emphasize that enough. It was really through great teamwork through our pharmacy division, interventional radiology, and the manufacturer. One of the biggest challenges was to work with the patient’s insurance to get this approved. Then, we had to coordinate how this would be administered, because this drug is given into the spinal fluid (via a lumbar puncture) through an intrathecal injection. It was daily messaging between me and these other groups to drive this.
What makes Swedish the right place for this advancement in ALS treatment?
It is a testament to what we can do at Swedish – we have a big system with lots of expertise. In this particular effort our pharmacy was super helpful. Interventional radiology was also very helpful. Our hospital team and our other administrative partners who helped with this were also key. This could not have happened in a smaller system with less expertise. It takes a big organization, a lot of teamwork, a lot of resources. What's exciting is that in a place like Swedish, this type of work and delivering new cutting-edge treatments is possible.
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