Qalsody slows ALS disease progression in real-world settings

Therapy was conditionally approved in US for patients with SOD1 mutation

Steve Bryson, PhD avatar

by Steve Bryson, PhD |

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Treatment with Qalsody (tofersen) in the real world slowed disease progression in people with amyotrophic lateral sclerosis (ALS) caused by SOD1 mutations, a small study reports.

It also stabilized patients’ quality of life and lowered levels of nerve damage-related biomarkers, which is consistent with clinical trial data that supported its approval.

“Treatment with [Qalsody] was shown to be an effective therapeutic approach,” the researchers wrote in “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,” which was published in eClinicalMedicine.

Qalsody was conditionally approved in the U.S. in 2023 for ALS patients who harbor mutations in the SOD1 gene, which are associated with up to 20% of familial ALS cases and about 2% of sporadic cases. Last month, a committee of the European Medicines Agency (EMA) recommended 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 Phase 1/2/3 VALOR trial (NCT02623699) and its ongoing open-label extension study (NCT03070119), 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.

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Qalsody in real-world settings

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’ 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.

“Based on preexisting evidence, treatment with tofersen in SOD1-ALS leads to a reduction in neurofilament levels (NfL),” the scientists wrote. “This study provides evidence that these findings can be extended to pNfH in CSF.”

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’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.