The U.S. Food and Drug Administration (FDA) has granted conditional approval to Biogen’s tofelsen (now named Qalsody) to treat mutations associated with amyotrophic lateral sclerosis (ALS). SOD1 gene.
The decision marks the first conditional approval of ALS in the country and comes approximately eight months after the regulatory agency received an application for review under the accelerated approval pathway. That pathway allows the FDA to grant conditional marketing approval to drugs based on early clinical trial data that suggests potential benefit.
The approval of Qalsody was based on biomarker data from the Phase 1/2/3 VALOR clinical trial (NCT02623699) and its open-label extension study (NCT03070119). The data showed that the treatment led to a marked reduction in blood levels of neurofilament light chain (NfL), a marker of nerve cell damage.
“The findings are highly likely to predict clinical benefit for patients,” the FDA said in a press release announcing the approval, adding, “Observed reductions in NfL varied by gender, duration of disease from onset, and site. was consistent across all subgroups based on onset and use of other drugs for the treatment of ALS.”
“For more than a decade, Biogen has been steadfast in its quest for a cure for ALS. We thank the scientists and the entire ALS community for their tireless efforts to provide this type of therapy. To people with SOD1-ALS,” said Christopher A., President and CEO of Biogen. ALS News Today“Today is also a pivotal moment in ALS research, as we are the first to reach consensus that neurofilaments can be used as surrogate markers that are likely to reasonably predict clinical benefit in SOD1-ALS. We believe this important scientific breakthrough will further accelerate the development of innovative medicines for ALS.”
European regulators are now considering the application of Qalsody for the EU
Members of the FDA’s Peripheral and Central Nervous System Drugs Advisory Committee last month were divided on whether the available data provided substantial evidence that Qalsody is effective in patients with SOD1-ALS. .
However, experts unanimously believe that NfL levels are a good surrogate marker of a drug’s efficacy, which seems to have favored early approval.
According to the FDA’s announcement, this treatment is now approved at the recommended dose of 100 mg. It is given by injection into the spinal canal, called an intrathecal injection, and contains 15 mL of solution. His first 3 doses are given him 2 weeks apart, then maintenance doses are given monthly.
We don’t have any information about Qalsody’s list price or release date yet.
A similar application for drug approval is being reviewed by the European Medicines Agency.
Meanwhile, the treatment is available in 34 countries through an early access program, Biogen said.
mutation of SOD1 This gene is found in 20% of familial ALS patients and up to 2% of sporadic ALS patients. Such mutations result in a toxic form of her SOD1 protein that accumulates and forms clumps that damage nerve cells.
Qalsody, administered by intrathecal injection, is designed to reduce SOD1 levels and preserve neuronal function.it does it by targeting SOD1messenger RNA (mRNA) – an intermediate molecule derived from DNA that induces the production of proteins – for degradation.
By reducing the amount of SOD1 protein produced in cells, this therapy may slow disease progression and prolong survival.
Approval of Qalsody in the US is based on data from a Phase 1 study (NCT03764488) in healthy volunteers, as well as results from the VALOR trial and its open-label extension in patients with ALS.
In the phase 1/2 part of VALOR, Qalsody, administered in single and multiple escalating doses, was generally well tolerated and improved SOD1 and NfL levels in cerebrospinal fluid, the fluid that surrounds the brain and spinal cord. was found to be able to reduce
An exploratory analysis also suggested that this treatment may slow the progression of ALS, with patients receiving the currently approved 100 mg dose compared to those receiving placebo , slows the decline in functional capacity, lung function, and muscle strength over 12 weeks.
Additional Qalsody research already underway
The Phase 3 portion of VALOR was designed to confirm the drug’s benefit in a larger patient group. 108 participants were enrolled and randomly assigned to receive either 100 mg of her Qalsody or placebo he received 8 intrathecal injections over 6 months.
The primary goal was to assess changes in functional impairment in 60 participants who had rapidly progressed ALS after 28 weeks or approximately 7 months.
Although that goal was not met, the researchers did see some trends towards lower lung function and muscle strength. In addition, SOD1 and NfL CSF levels were significantly reduced in patients receiving Qalsody.
After completing the Phase 3 part of VALOR, a total of 95 participants elected to participate in the open-label extension study. All participants in the trial received Qalsody for up to seven years. This study he plans to complete in June 2024.
One-year data spanning the Phase 3 and extension studies showed that this treatment resulted in a significant and clinically meaningful delay in the progression of ALS.
Compared with patients initially assigned to placebo who switched to Qalsody in the extension trial, patients who consistently used Qalsody for 1 year experienced a smaller decline in ALSFRS-R score, 6 vs. 9.5.
Significant differences between these groups were also observed in measures of lung function and muscle strength. The early-start group also significantly increased survival and time to death or permanent ventilation.
An additional analysis showed that lower blood NfL levels within the first 4 months of treatment predicted slower decline in ALSFRS-R scores up to 6.5 months. These early declines were also associated with slower declines in other measures of function and disease severity.
This finding prompted the FDA’s Advisory Panel to unanimously consider blood NfL levels as a good surrogate measure of Qalsody efficacy in patients with ALS, allowing the FDA to quickly identify available biomarker data. It may have contributed to deeming it sufficient to support authorization.
An ongoing Phase 3 trial called ATLAS (NCT04856982) is currently evaluating the clinical benefit of Qalsody in patients. SOD1 A mutation associated with rapidly progressing ALS. These participants have not yet experienced symptoms, but show signs of neuronal damage defined by elevated NfL levels.
A total of 150 adults will be enrolled at approximately 30 sites worldwide. They will be randomly assigned to receive either her Qalsody (100 mg) or placebo on the approved schedule. In the first month she had three intrathecal injections and then monthly injections. Up to 2 years.
The primary goal is to determine whether treatments can prevent patients from developing symptoms of ALS. Topline data he is due in 2026.