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Treatment with <a href="https://alsnewstoday.com/ionis-sod1-rx-biib067/">Qalsody</a> (tofersen) in the real world slowed disease progression in people with <a href="https://alsnewstoday.com/what-is-als/">amyotrophic lateral sclerosis</a> (ALS) caused by SOD1 mutations, a small study reports.
It also stabilized patients&#8217; quality of life and lowered levels of nerve damage-related biomarkers, which is consistent with clinical trial data that supported its approval.
&#8220;Treatment with [Qalsody] was shown to be an effective therapeutic approach,&#8221; the researchers wrote in “<a href="https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(24)00074-9/fulltext">Effects of tofersen treatment in patients with SOD1-ALS in a “real-world” setting – a 12-month multicenter cohort study from the German early access program</a>,” which was published in eClinicalMedicine.
Qalsody was <a href="https://alsnewstoday.com/news/fda-approves-tofersen-now-qalsody-treatment-adults-sod1-als/">conditionally approved in the U.S.</a> in 2023 for ALS patients who harbor mutations in the SOD1 gene, which are associated with up to 20% of <a href="https://alsnewstoday.com/forms-of-als/familial-als/">familial ALS</a> cases and about 2% of <a href="https://alsnewstoday.com/forms-of-als/sporadic-als/">sporadic</a> cases. Last month, a committee of the European Medicines Agency (EMA) <a href="https://alsnewstoday.com/news/committee-favors-eu-approval-qalsody-1st-treatment-sod1-als/">recommended</a> that Qalsody be approved in the European Union under exceptional circumstances.
The therapy, which is administered intrathecally, that is, directly into the spinal canal, suppresses the production of mutant SOD1 protein to slow disease progression and extend survival.
Its applications in the U.S. and Europe were based on data from the three-part <a href="https://www.clinicaltrials.gov/ct2/show/NCT02623699">Phase 1/2/3 VALOR trial (NCT02623699)</a> and its ongoing <a href="https://clinicaltrials.gov/ct2/show/NCT03070119">open-label extension study (NCT03070119)</a>, where Qalsody slowed disease progression, extended survival, and lowered neurofilament light chain (NfL), a marker of nerve damage.
Early access programs (EAPs) were launched in a number of countries based on the findings to provide Qalsody to SOD1-ALS patients outside of clinical trials before its regulatory approval.
[recommended-reading id=90434]
<h3>Qalsody in real-world settings</h3>
Here, researchers report on data from 24 SOD1-ALS patients who received Qalsody under an EAP in Germany between March 2022 and April 2023.
The patients received a median of eight Qalsody doses over a median observation period of six months. Of them, half were women and 58.3% had a family history of the disease.
The median rate of progression, as assessed using the ALS Functional Rating Scale Revised (ALSFRS-R), was slower with Qalsody than at the start of the study, or its baseline. Patients lost a median of 0.11 ALSFRS-R points a month after starting treatment compared with 0.41 monthly points before starting Qalsody.
Seventeen patients had a slower progression rate with treatment compared with the baseline and six had a faster progression.
Those with a faster progression had a shorter disease duration at the time they started Qalsody and higher levels of nerve damage biomarkers, including NfL and phosphorylated neurofilament heavy chain (pNfH). These patients&#8217; observation period was also shorter, “implying that they have received fewer doses of Qalsody,” the researchers wrote. No changes in muscle strength were seen in nine patients with available data.
Self-reported quality of life showed stable results among eight evaluable patients. The participants generally indicated severe problems with mobility and self-care, and slight to moderate levels of pain, discomfort, anxiety, and depression.
Other measures deteriorated from moderate to severe during treatment, including the ability to perform work, study, housework, and family or leisure activities. No changes were observed when the patients were asked to indicate their current state of health on a scale from 0 to 100, however.
In contrast, blood levels of NfL and spinal fluid levels of pNFH significantly dropped with treatment, indicating reduced nerve cell damage.
&#8220;Based on preexisting evidence, treatment with tofersen in SOD1-ALS leads to a reduction in neurofilament levels (NfL),&#8221; the scientists wrote. &#8220;This study provides evidence that these findings can be extended to pNfH in CSF.&#8221;
Two potentially treatment-related serious side effects were reported. One patient was diagnosed with autoimmune-related inflammation of the spinal cord, or myeloradiculitis, and another had short-term weakness in the lower limbs. Both discontinued treatment. No other drug-related side effects were reported, other than those related to the therapy&#8217;s administration into the spinal canal, such as lower back pain, headache, and pain, weakness, numbness, and tingling in the lower limbs.
“The findings of this study suggest that treatment of SOD1-ALS patients with intrathecal administration of [Qalsody] is an effective therapeutic approach,” the researchers wrote.

Qalsody slows ALS disease progression in real-world settings

Health Canada is now reviewing <a href="https://alsnewstoday.com/ionis-sod1-rx-biib067/">Qalsody</a> (tofersen) as a potential treatment for people with <a href="https://alsnewstoday.com/what-is-als/">amyotrophic lateral sclerosis</a> (ALS) who carry mutations in the SOD1 gene, according to the therapy&#8217;s developer <a href="https://www.biogen.com/">Biogen</a>.
The Canadian regulatory authority agreed to review Biogen&#8217;s application for the therapy&#8217;s approval, with its decision expected in early 2025, according to a <a href="https://www.newswire.ca/news-releases/health-canada-accepts-for-review-new-drug-submission-for-tofersen-for-treatment-of-rare-genetic-form-of-als-806869519.html">company press release</a>.
If approved, Qalsody will become the first and only therapy approved in Canada to target a genetic cause of ALS. Qalsody already is <a href="https://alsnewstoday.com/news/fda-approves-tofersen-now-qalsody-treatment-adults-sod1-als/">approved in the U.S.</a> and has been <a href="https://alsnewstoday.com/news/committee-favors-eu-approval-qalsody-1st-treatment-sod1-als/">recommended for approval</a> in the European Union to treat ALS-SOD1 patients.
The application &#8220;represents a critical milestone for the Canadian ALS community and those suffering from this ultra-rare genetic form of the disease that robs them of time with loved ones,&#8221;said Eric Tse, vice president and general manager of Biogen Canada.
&#8220;For over a decade, Biogen has been committed to advancing ALS research to provide a deeper understanding of this devastating disease. We are passionate about doing what we can to make a difference and are deeply committed to the rare disease community,&#8221; Tse added.
[recommended-reading id=79512]
<h3>Request for approval based on data from VALOR trial</h3>
Mutations in the SOD1 gene are found in as many as 20% of people with <a href="https://alsnewstoday.com/forms-of-als-familial-als/">familial ALS</a> and in up to 2% of <a href="https://alsnewstoday.com/sporadic-als/">sporadic ALS</a> cases. These mutations lead to the production of an abnormal SOD1 protein, which tends to accumulate and form toxic clumps inside nerve cells, causing damage.
Qalsody belongs to a class of therapies called antisense oligonucleotides, or ASOs. Such therapies prevent the production of disease-causing proteins by interfering with their messenger RNA (mRNA) — an intermediate molecule derived from DNA that&#8217;s used as a template for protein production.
The drug is designed to bind to SOD1&#8217;s mRNA and target it for degradation, preventing the cell&#8217;s protein-making machinery from reading this template to produce the protein. This causes a marked reduction in SOD1 levels, which is expected to slow disease progression and extend survival.
The treatment is administered via intrathecal injection, or an injection into the spinal canal. In the U.S., it&#8217;s given as three initial three doses 14 days apart, followed by maintenance doses every 28 days.
Qalsody&#8217;s submission to Health Canada was based on data from Part 3 of the <a href="https://clinicaltrials.gov/study/NCT02623699">VALOR trial (NCT02623699)</a>, which enrolled 108 adults with ALS and a confirmed SOD1 mutation. It aimed to assess the safety and efficacy of Qalsody versus a placebo.
Participants were randomly assigned to receive eight intrathecal injections of either 100 mg of Qalsody or a placebo over six months.
The trial&#8217;s main goal was to assess changes in functional disability, as measured with the ALS Functional Rating Scale-Revised (ALSFRS-R), in a group of 60 patients with fast-progressing disease after about seven months.
That goal <a href="https://alsnewstoday.com/news/phase-3-tofersen-trial-fails-slow-sod1-als-trends-hopeful-valor-trial/">was not met</a>, but there were some indications that Qalsody slowed the decline in measures of lung function and muscle strength. Also, the treatment <a href="https://alsnewstoday.com/news/early-tofersen-treatment-may-slow-sod1-progression-valor-study/">significantly reduced</a> spinal fluid levels of SOD1 and blood levels of neurofilament light chain (NfL), a marker of nerve cell degeneration, both of which increased in the placebo group.
After completing the trial, 95 participants joined an <a href="https://clinicaltrials.gov/study/NCT03070119">open-label extension study (NCT03070119)</a>, in which all are receiving Qalsody for up to seven years. That study is expected to be concluded in June.
After one year, data from the Phase 3 study and its extension showed that patients who were always on Qalsody experienced a smaller drop in their ALSFRS-R scores relative to those who were initially assigned to the placebo and then switched to the treatment in the extension study. That decline averaged six points for those always treated versus 9.5 points for patients who switched from the placebo.
The early-start group also showed significant extensions in survival and in time to death or permanent ventilation.
A Phase 3 trial called <a href="https://clinicaltrials.gov/study/NCT04856982">ATLAS (NCT04856982)</a>, launched in 2021, is now testing whether Qalsody can delay the onset of disease symptoms in individuals with a SOD1 mutation who already show signs of neuronal damage —  specifically, who have elevated blood levels of NfL — but are asymptomatic.
The trial, slated to run through 2027, is expected to involve about 150 patients who receive the treatment or a placebo for up to two years. Top-line data also is anticipated in 2027.

Health Canada now reviewing Qalsody as treatment for SOD1-ALS

An advisory committee of the European Medicines Agency (EMA) has recommended that Biogen&#8217;s <a href="https://alsnewstoday.com/ionis-sod1-rx-biib067/">Qalsody</a> (tofersen) be approved in the European Union under exceptional circumstances to treat adults with <a href="https://alsnewstoday.com/what-is-als/">amyotrophic lateral sclerosis</a> (ALS) associated with SOD1 gene mutations.
The positive opinion from the Committee for Medicinal Products for Human Use, known as CHMP, is based on clinical and biomarker data from the <a href="https://clinicaltrials.gov/study/NCT02623699">Phase 1/2/3 VALOR clinical trial (NCT02623699)</a>, which altogether tested Qalsody in more than 175 patients. Overall, the treatment candidate led to a 60% reduction in blood levels of neurofilament light chain (NfL), a marker of nerve cell damage.
An approval under exceptional circumstances can be recommended for therapies with a positive risk-benefit, but where comprehensive data are unlikely to be obtained given the rarity of the disease. The recommendation now will be reviewed by the European Commission, with a decision expected between April and June.
If approved, Qalsody will become the first therapy authorized in the European Union to target a genetic cause of ALS.
“The CHMP’s positive opinion reinforces the impact Qalsody can have in SOD1-ALS and further demonstrates Biogen’s commitment to address the unmet needs of people living with ALS and neuromuscular diseases,” Priya Singhal, MD, <a href="https://www.biogen.com/">Biogen</a>’s head of development, said in a <a href="https://investors.biogen.com/news-releases/news-release-details/biogens-qalsodyr-tofersen-first-therapy-treat-rare-genetic-form">company press release</a>.
[recommended-reading id=78763]
<h3>Qalsody approved in US in 2023, also for use in adults</h3>
In the U.S., Qalsody early last year was <a href="https://alsnewstoday.com/news/fda-approves-tofersen-now-qalsody-treatment-adults-sod1-als/">granted conditional approval</a> to treat adults with SOD1-ALS. The U.S. Food and Drug Administration&#8217;s decision also marked the the first conditional approval of a treatment for this form of ALS in that country.
Per the <a href="https://www.biogencdn.com/us/pdfs/qalsody-prescribing-information.pdf">medication&#8217;s label</a>, injections are given monthly into the spinal canal, or intrathecally, following three initial doses given two weeks apart.
Experts welcomed the positive opinion from the CHMP.
“This is a significant milestone for the entire ALS community — for the first time we have a treatment that led to sustained reductions in neurofilament, a marker of [nerve cell] injury and neurodegeneration,” said Philip Van Damme, MD, PhD, professor of neurology and director of the Neuromuscular Reference Center at the University Hospital Leuven, in Belgium.
<a href="https://alsnewstoday.com/als-and-genetics/">Mutations in the SOD1 gene</a> are found in as many as 20% of people with <a href="https://alsnewstoday.com/forms-of-als-familial-als/">familial ALS</a> and up to 2% of people with <a href="https://alsnewstoday.com/sporadic-als/">sporadic ALS</a>, where there&#8217;s no known family history of the disease. Such mutations result in a toxic form of the SOD1 protein, which is prone to form toxic clumps that accumulate and damage nerve cells.
[quote=&#8221;center&#8221;]This is a significant milestone for the entire ALS community — for the first time we have a treatment that led to sustained reductions in neurofilament, a marker of [nerve cell] injury and neurodegeneration.[/quote]
To produce the SOD1 protein, SOD1&#8216;s genetic code is used to form an intermediate molecule called messenger RNA, or mRNA. The mRNA then is shipped from the nucleus to the cell&#8217;s protein-making machinery, where it is used as a template for making SOD1.
Qalsody belongs to a class of therapies called antisense oligonucleotides (ASOs), and is designed to bind to SOD1&#8216;s mRNA and promote its degradation. That allows it to halt the production of the mutated SOD1 protein. By doing so, the therapy is expected to reduce toxic SOD1 clumps, slow disease progression, and potentially extend survival in SOD1-ALS patients.
[recommended-reading id=83790]
<h3>Treatment found to slow ALS progression in VALOR study</h3>
The three-part VALOR study, started in 2016, investigated Qalsody in a total of 176 ALS patients carrying SOD1 mutations.
In its Phase 1/2 parts, the therapy — then still known as tofersen — was found to be <a href="https://alsnewstoday.com/news/tofersen-safe-appears-to-slow-disease-progression-in-sod1-als-patients-phase-1-2-trial-shows/">generally safe and well tolerated</a> when given in single or multiple ascending doses. It also was shown to have the ability to reduce SOD1 and NfL levels in the spinal fluid.
The Phase 3 part then enrolled 108 patients who were randomly assigned to receive eight intrathecal injections of Qalsody (100 mg), or a placebo, given over six months. The main goal of this part was to assess changes in functional disability among the 60 patients with rapidly progressing ALS, after 28 weeks, or about seven months.
While the trial failed to meet its goal, trends supporting Qalsody were observed in some secondary measures, including muscle strength, quality of life , and lung function. Also, the medication resulted in <a href="https://alsnewstoday.com/news/early-tofersen-treatment-may-slow-sod1-progression-valor-study/">marked drops</a> in blood NfL levels — by 60% compared with a placebo.
After completing VALOR, participants could enter an <a href="https://clinicaltrials.gov/study/NCT03070119">open-label extension study (NCT03070119)</a>, which is still ongoing, wherein all are receiving Qalsody for up to seven years.
One-year data including the Phase 3 trial and the extension study showed the treatment led to a significant and clinically meaningful slowing of ALS progression. Specifically, those who started on the medication in VALOR had a 6-point decline in ALS Functional Ratings Scale-Revised (ALSFRS-R) scores versus a 9.5-point decline for those who were initially on a placebo.
The most common side effects in Qalsody-treated patients included muscle and joint pain, fatigue, fever, and increased levels of white blood cells and proteins in the spinal fluid.
The therapy now is also being tested in the <a href="https://www.clinicaltrials.gov/study/NCT04856982">ATLAS Phase 3 trial (NCT04856982)</a>. That global study is evaluating whether Qalsody can delay the onset of ALS symptoms in patients with a SOD1 mutation who already show signs of neuronal damage, as defined by elevated NfL levels. It&#8217;s slated to run through 2027.
“We are proud to help pioneer the role of neurofilament in SOD1-ALS clinical trials and are deeply grateful to the people living with SOD1-ALS, their loved ones and study care teams for their dedication to furthering research for the ALS community,” Singhal said.

Committee favors EU approval of Qalsody for adults with SOD1-ALS

Throughout 2023, <a href="https://alsnewstoday.com/">ALS News Today</a> brought you daily coverage of the latest clinical research and scientific breakthroughs related to <a href="https://alsnewstoday.com/what-is-als/">amyotrophic lateral sclerosis</a> (ALS).
Here are the year&#8217;s top 10 most-read articles, each with a brief description. We&#8217;re excited to remain a dependable resource for the ALS community in 2024.
<h3>No. 10 – Omega-3 fatty acid slows ALS progression, extends survival</h3>
A diet rich in omega-3 fatty acids has been tied to a lower risk of developing ALS, but whether it also might affect the rate of disease progression is not known. Researchers at Harvard found that <a href="https://alsnewstoday.com/news/alpha-linolenic-acid-slower-als-progression-better-survival/">higher blood levels of alpha-linolenic acid</a> (ALA) — an omega-3 fatty acid found in flaxseed, walnuts, chia, canola, and soybean oils — linked with a slower disease progression and a 50% lower risk of death.
Two other fatty acids also were tied to a lower mortality risk. This discovery suggests that adding to the diet more foods containing these fatty acids could be beneficial for ALS patients. Researchers hope to confirm these findings in a clinical trial.
<h3>No. 9 – Further questions set back European approval of AMX0035</h3>
Amylyx Pharmaceuticals&#8217; application seeking the approval of AMX0035 in treating ALS patients across Europe faced <a href="https://alsnewstoday.com/news/european-approval-amx0035-als-faces-new-hurdle-review/">a second round of questions</a> from the Committee for Medicinal Products for Human Use (CHMP), an arm of the European Medicines Agency. The committee still had major objections to AMX0035 that needed to be addressed, after a scientific advisory group meeting of experts provided recommendations based on current data.
The therapy is approved in the U.S. and available under the brand name <a href="https://alsnewstoday.com/amx0035/">Relyvrio</a> (sodium phenylbutyrate and taurursodiol), and approved in Canada as Albrioza. CHMP,  however, later confirmed that it <a href="https://alsnewstoday.com/news/chmp-confirms-initial-recommendation-not-approve-amx0035-eu/">remained opposed to AMX0035&#8217;s approval in Europe</a>.
<h3>No. 8 – Masitinib as add-on therapy seen to benefit mild to moderate ALS</h3>
<a href="https://alsnewstoday.com/masitinib/">Masitinib</a> is an experimental ALS therapy that intends to slow disease progression and ease <a href="https://alsnewstoday.com/symptoms-of-als/">ALS symptoms</a> by blocking certain enzymes needed by immune cells thought to drive inflammation and neurodegeneration in ALS. An analysis of AB Science&#8217;s completed <a href="https://clinicaltrials.gov/ct2/show/NCT02588677">AB10015 Phase 2/3 clinical trial (NCT02588677)</a> showed that treatment with masitinib as an add-on to <a href="https://alsnewstoday.com/rilutek-riluzole-for-als/">Rilutek</a> (riluzole) benefited most of its <a href="https://alsnewstoday.com/news/als-therapy-masitinib-works-best-add-on-moderate-disease-analysis/">ALS patients with mild to moderate disease severity</a>.
Although the 48-week study failed to show better survival rates overall with masitinib compared with a placebo, treated patients with moderate ALS experienced a 25-month extension in survival. The combination treatment also significantly slowed disease progression, improved lung function, and enhanced life quality for patients who still retained some degree of physical function at the study&#8217;s start.
<h3>No. 7 – Stem cell transplants seen to extend survival by 4 years</h3>
A stem cell transplant using mesenchymal stromal cells (MSCs) taken from bone marrow <a href="https://alsnewstoday.com/news/msc-stem-cell-transplants-extend-survival-4-years-als-patients/">significantly extended survival for ALS patients</a> beyond their anticipated lifespan, a new analysis of data from two Phase 1 trials, both conducted in the early 2000s, showed.
Treated patients lived about 118 months, or nearly 10 years, without needing permanent breathing support, surpassing a predicted survival time of around 70 months by about four years. At the time of the analysis, four of the trials&#8217; 19 total patients were alive, including one still living without any need for breathing or feeding assistance at 303 months — more than 20 years later.
<h3>No. 6 – Neurologists frustrated with current ALS treatments</h3>
Neurologists, while quick to prescribe their patients new treatments showing a potential to delay ALS progression in clinical trials, often <a href="https://alsnewstoday.com/news/neurologists-frustrated-with-als-treatments-now-on-market-study/">remain frustrated with current available therapies</a>. Fewer than 20% of these doctors responding to a survey expressed full satisfaction with responses to treatments now on the market.
This so-called first market landscape study on ALS, conducted by Spherix Global Insights, involved 103 neurologists. It found that many already were prescribing Relyvrio and <a href="https://alsnewstoday.com/ionis-sod1-rx-biib067/">Qalsody</a> (tofersen), two ALS medications recently approved in the U.S. Spherix data also showed that neurologists lacked awareness of <a href="https://alsnewstoday.com/experimental-treatments-for-als/">experimental ALS treatments</a>, possibly because many such therapies fail to win approval.
<h3>No. 5 – COYA 302 seen to slow ALS progression in proof-of-concept trial</h3>
COYA 302, an experimental immune-modulating therapy under development by Coya Therapeutics, markedly <a href="https://alsnewstoday.com/news/mda-2023-coya-302-therapy-slows-als-progression-early-trial/">slowed disease progression among four ALS patients</a> treated in a small, 48-week proof-of-concept clinical trial. Data also showed a treatment-related increase in the activity of <a href="https://alsnewstoday.com/tregs/">regulatory T-cells</a>, an anti-inflammatory immune cell, demonstrating that the therapy worked as designed.
Coya intends to open larger ALS trials of the therapy, administered via a subcutaneous (under-the-skin) injection. The company announced plans to file early this year a request for clearance to <a href="https://alsnewstoday.com/news/coya-dr-reddys-collaborate-advance-coya-302-als-therapy-globally/">launch a Phase 2 clinical study</a>.
<h3>No. 4 – Tofersen, now Qalsody, approved by the FDA for SOD1-ALS</h3>
In April, the <a href="https://alsnewstoday.com/news/fda-approves-tofersen-now-qalsody-treatment-adults-sod1-als/">U.S. Food and Drug Administration conditionally approved</a> Biogen&#8217;s Qalsody (tofersen) for treating ALS linked to SOD1 gene mutations. The decision marked the country&#8217;s first conditional approval for an ALS therapy.
Qalsody&#8217;s approval relied on biomarker data from the <a href="https://clinicaltrials.gov/ct2/show/NCT02623699">VALOR Phase 1/2/3 clinical trial (NCT02623699)</a> and its <a href="https://clinicaltrials.gov/ct2/show/NCT03070119">extension study (NCT03070119)</a>. Data demonstrated significant, treatment-related reductions in blood neurofilament light chain (NfL) levels, indicating a decline in nerve cell damage. Exploratory analyses also suggested the treatment&#8217;s use could slow ALS progression, particularly in people with rapidly progressing disease.
<h3>No. 3 – Chinese herbal skin patch, as add-on therapy, slows progression</h3>
A skin patch containing a mixture of Chinese herbs called Ji Wu Li (JWL), combined with standard treatments, <a href="https://alsnewstoday.com/news/herbal-skin-patch-add-on-therapy-slows-als-progression/">significantly slowed ALS progression</a> in a placebo-controlled clinical trial involving 120 adult patients. Benefits were seen after eight weeks of treatment and sustained for up to 20 weeks, or about five months.
Administered via a self-adhesive patch placed on the patient&#8217;s upper back, the transdermal, or on-the-skin, therapy may provide a way to deliver a concentrated formulation of JWL without swallowing, which can be challenging for some with ALS. Use of the patch, worn for six consecutive days each week and for six hours each day, also was reported to slow quality of life declines and ease weight loss.
<h3>No. 2 – Gene editing &#8216;cuts out&#8217; ALS-linked mutation in early study</h3>
In mouse models and human cells, the gene-editing tool CRISPR/Cas9 <a href="https://alsnewstoday.com/news/crispr-cas9-gene-editing-used-cut-out-mutation-early-study/">removed the repeat expansion defect in the C9ORF72 gene</a>, the most common genetic cause of ALS, scientists in a proof-of concept study reported.
While not interfering with the production of the C9ORF72 protein, such gene editing notably lowered levels of defective RNA molecules and small proteins associated with nerve cell death in ALS. RNA acts as the intermediary molecule derived from a DNA sequence, functioning as a template for protein production.
<h3>No. 1 – Poorer ALS survival linked with higher &#8216;good&#8217; cholesterol levels</h3>
A Netherlands-based population review study found that elevated levels of high-density lipoprotein, also known as &#8220;good&#8221; cholesterol, <a href="https://alsnewstoday.com/news/lower-als-survival-ratel-linked-higher-good-cholesterol-levels/">significantly correlated with a reduced survival rate</a> in people with ALS. Individuals in more advanced disease stages also were seen to have lower levels of total cholesterol and low-density lipoprotein, commonly referred to as &#8220;bad&#8221; cholesterol.
Its researchers acknowledged their study contrasts with previous research suggesting that a <a href="https://alsnewstoday.com/news/higher-good-cholesterol-blood-levels-linked-lower-als-risk/">lower ALS risk was tied to higher levels of good cholesterol</a>. Still, its findings contribute to insights into fat-like lipid metabolism and ALS severity, as their levels appear to be related to disease progression.
***
At ALS News Today, we hope our stories and reporting throughout 2023 positively impacted the lives of those affected by ALS. We look forward to serving the community further in 2024, seeking to provide ongoing support and information.
A very happy new year to all our readers!

Spinal taps can be given safely to ALS patients, small study reports

The recent conditional approval of <a href="https://alsnewstoday.com/ionis-sod1-rx-biib067/">Qalsody</a> (tofersen) for adults with <a href="https://alsnewstoday.com/what-is-als/">amyotrophic lateral sclerosis</a> (ALS) who carry mutations in the SOD1 gene is a major cause for celebration, according to the <a href="https://www.mda.org/">Muscular Dystrophy Association</a> (MDA).
The therapy <a href="https://alsnewstoday.com/news/fda-approves-tofersen-now-qalsody-treatment-adults-sod1-als/">earned accelerated approval</a> from the U.S. Food and Drug Administration (FDA) last week, making it the first to target a genetic cause of the disease to be approved.
The organization funded early research toward developing Qalsody for SOD1-associated ALS, which is estimated to affect about 330 people in the U.S. Its approval gives people with this rare form of the disease a new &#8220;treatment option,&#8221; according to the MDA.
“The approval of Qalsody is a turning point in therapy development for ALS as it represents the first therapy to target a genetic cause of the disease,” Sharon Hesterlee, PhD, chief research officer at MDA, said in a <a href="https://www.globenewswire.com/news-release/2023/04/25/2654417/0/en/Muscular-Dystrophy-Association-Celebrates-FDA-Approval-of-Biogen-s-Qalsody-for-Treatment-of-SOD1-ALS.html">press release from the organization</a>. &#8220;It’s gratifying to see a strategy that we and other organizations funded substantially in earlier stages maturing into a real solution for people living with this genetic form of ALS. It represents the fulfillment of the promise of effective genetic medicines for ALS patients and their families.&#8221;
Qalsody is expected to  be available to healthcare providers in the U.S. in the coming days, although its availability may vary as providers learn about it and adopt its use in their individual clinics, Biogen, the therapy&#8217;s developer, said in a <a href="https://investors.biogen.com/news-releases/news-release-details/fda-grants-accelerated-approval-qalsodytm-tofersen-sod1-als">press release announcing</a> the approval.
The company has launched a patient support services program, which can be accessed on the <a href="https://www.qalsody.com/">therapy&#8217;s website</a>. The program supports patients as part of their treatment, providing financial and insurance assistance, as well as education about the therapy.
“Since SOD1 mutations were first identified as a cause of ALS 30 years ago, the familial ALS community has been searching for genetically targeted treatments. Qalsody offers families who have lost generation after generation in the prime of their life to this devastating disease a therapy targeting the underlying cause of SOD1-ALS,&#8221; said Jean Swidler, chair of Genetic ALS &amp; FTD: End the Legacy.
Mutations in the SOD1 gene lead to the production of a toxic form of the SOD1 protein that forms clumps and causes nerve cell damage.
Qalsody is designed to lower SOD1 levels by targeting SOD1&#8216;s messenger RNA (mRNA) — an intermediate molecule needed for protein production — and marking it for degradation. Reducing the protein&#8217;s production should slow disease progression.
The therapy is approved at a dose of 100 mg via intrathecal injection — into the spinal canal — once a month following two initial loading doses.
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<h3>What led to Qalsody&#8217;s approval?</h3>
About eight months ago, the FDA <a href="https://alsnewstoday.com/news/fda-expected-decide-tofersen-approval-sod1-als-january/">agreed to review</a> Qalsody under its accelerated approval pathway, which lets it give conditional approval to a treatment based on early clinical trial data that indicates it&#8217;s safe and likely efficacious.
The FDA&#8217;s decision was based largely on biomarker data from the <a href="https://clinicaltrials.gov/ct2/show/NCT02623699">Phase 1/2/3 VALOR clinical trial (NCT02623699)</a> and its ongoing <a href="https://clinicaltrials.gov/ct2/show/NCT03070119">open-label extension study (NCT03070119)</a> that showed significant <a href="https://alsnewstoday.com/news/early-tofersen-treatment-may-slow-sod1-progression-valor-study/">reductions in blood levels of neurofilament light chain</a> (NfL), a biomarker of nerve cell damage.
The Phase 3 data indicated Qalsody <a href="https://alsnewstoday.com/news/phase-3-tofersen-trial-fails-slow-sod1-als-trends-hopeful-valor-trial/">failed to slow functional declines</a> for patients, however, but additional data spanning the trial and the extension phase showed <a href="https://alsnewstoday.com/news/early-tofersen-treatment-may-slow-sod1-progression-valor-study/">slower disease progression</a> for those who&#8217;d been using it longer. Moreover, early reductions in blood NfL levels were predictive of <a href="https://alsnewstoday.com/news/fda-approves-tofersen-now-qalsody-treatment-adults-sod1-als/#:~:text=predicted%20slower%20reductions%20in%20ALSFRS%2DR%20scores">slower functional declines</a>.
An FDA advisory committee last month <a href="https://alsnewstoday.com/news/panel-favors-tofersen-biomarker-data-mixed-on-efficacy-sod1-als/">unanimously agreed</a> these NfL level reductions were likely able to predict the treatment&#8217;s clinical efficacy, which may have supported the FDA&#8217;s ultimate approval.
Qalsody is now the first ALS therapy to be approved based on biomarker data.
“We’re excited to celebrate this milestone which brings the very first targeted treatment option to the SOD1-ALS community. This approval shows the FDA acting flexibly and progressively by using the accelerated approval pathway, innovative trial designs, and listening to the patient community to determine this treatment is safe and effective,&#8221; said Paul Melmeyer, vice president of public policy and advocacy at the MDA.
<h3>Continued Qalsody approval hinges on additional data</h3>
Qalsody&#8217;s continued approval may be contingent on additional data that supports its efficacy. Data from the ongoing <a href="https://clinicaltrials.gov/ct2/show/NCT04856982">Phase 3 ATLAS (NCT04856982)</a> trial are expected to fulfill that requirement.
ATLAS is <a href="https://clinicaltrials.gov/ct2/show/NCT04856982#contacts">recruiting</a> about 150 adults with SOD1 mutations associated with rapidly progressing ALS. Eligible participants will not yet have symptoms, but will show signs of nerve cell damage, reflected by high NfL levels.
Participants will be randomly assigned to receive either Qalsody (100 mg) or a placebo at the approved dosing schedule for up to two years, with the main goal being to determine whether the treatment can prevent symptoms from emerging.
Top-line data are expected in 2026. More confirmatory trials may be needed if the findings aren&#8217;t positive.
While Qalsody&#8217;s approval covers adults with SOD1-ALS, Sunny Brous, founder of SunnyStrong and an ALS patient, said the approval benefits all ALS patients.
“Any win for a subgroup of ALS is a win for the entire community,&#8221; Brous said. &#8220;We are all thankful for steps towards a cure.”

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