NOW FDA APPROVED
The first and only approved treatment to target a genetic cause of amyotrophic lateral sclerosis (ALS)1
Approved under FDA accelerated approval pathway. See Indication.
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Clinical study information
Study 1 Part C (VALOR) pharmacodynamics
Biomarker analyses in the intent-to-treat (ITT) population
Total CSF SOD1, an indirect measure of target engagement, and NfL, a blood-based biomarker of axonal injury and neurodegeneration, were
evaluated in VALOR.
Effect of QALSODY on total CSF SOD1 protein
VALOR ITT population Week 28 reduction in CSF SOD1 protein (geometric mean ratio to baseline)1
Difference in geometric mean ratios for QALSODY to placebo: 34%; nominal p<0.0001
Effect of QALSODY on NfL protein
VALOR ITT population Week 28 change in NfL (geometric mean ratio to baseline)1
Difference in geometric mean ratios for QALSODY to placebo: 60%; nominal p<0.0001
Cardiac electrophysiology
At the maximum approved recommended dosing regimen, QALSODY does not prolong the QTc interval to any clinically relevant extent.
VALOR study design1
Baseline and disease characteristics in VALOR
Baseline disease characteristics in the ITT population (combined modified intent-to-treat [mITT] and non-mITT population) were generally similar in patients treated with QALSODY and patients who received placebo, with slightly shorter time from symptom onset and higher plasma NfL at baseline in the QALSODY group.1
*Concomitant riluzole and/or edaravone use was permitted for patients.
ALSFRS-R=Amyotrophic Lateral Sclerosis Functional Rating Scale–Revised; NfL=neurofilament light.
Primary efficacy analysis in VALOR1
The primary efficacy analysis was the change from baseline to Week 28 in the ALSFRS-R total score in the mITT population
The mITT population (n=60):
- Analyzed using the joint rank test to account for mortality in conjunction with multiple imputation to account for missing data for withdrawals other than death
- Had an SVC ≥65% of predicted value
- Met prognostic enrichment criteria for rapid disease progression, defined based on their pre-randomization ALSFRS-R decline slope and SOD1 mutation type
Patients treated with QALSODY experienced less decline from baseline in the ALSFRS-R compared to placebo but the results were not statistically significant (QALSODY-placebo adjusted mean difference [95% CI]: 1.2 [-3.2, 5.5]). Other clinical secondary outcomes also did not reach statistical significance.
Biomarker results in the ITT and mITT populations†
†Notes:
Note 1: N is the number of patients with baseline value.
Note 2: MI was used for missing data. Model included treatment, use of riluzole or edaravone, relevant baseline score and post-baseline values (natural log transformed data). Separate models for mITT and nonmITT were used and combined for ITT analyses.
Note 3: Adjusted geometric mean ratios to baseline, treatment differences in adjusted geometric mean ratios to baseline and corresponding 95% CIs and nominal p-values were obtained from the ANCOVA model for change from baseline including treatment as a fixed effect and adjusting for the following covariates: baseline disease duration since symptom onset, relevant baseline score, and use of riluzole or edaravone. The analysis was based on natural log transformed data.
Plasma NfL adjusted geometric mean ratio to baseline values in VALOR by study week for the ITT population
52-week interim VALOR OLE analysis
After completion of Study 1, patients had the option to enroll in an open-label extension study. At an interim analysis at 52 weeks, reductions in NfL were seen in patients previously receiving placebo who initiated QALSODY in the open-label extension study, similar to the reductions seen in patients treated with QALSODY in Study 1.
Earlier initiation of QALSODY compared to placebo/delayed initiation of QALSODY was associated with trends for reduction in decline on ALSFRS-R, SVC percent-predicted, and hand-held dynamometry (HHD) megascore that were not statistically significant.
Through all open-label follow-up at the time of the interim analysis, earlier initiation of QALSODY was also associated with a trend towards reduction of the risk of death or permanent ventilation, although it was not statistically significant.
These exploratory analyses should be interpreted with caution given the limitations of data collected outside of a controlled study, which may be subject to confounding.
Safety
Warnings and Precautions1
Myelitis and/or Radiculitis
Serious adverse reactions of myelitis and radiculitis have been reported in patients treated with QALSODY. Six patients treated with QALSODY experienced myelitis or radiculitis in the clinical studies. Two patients discontinued treatment with QALSODY and required symptomatic management with full resolution of symptoms. In the remaining 4 patients, symptoms resolved without discontinuation of QALSODY. If symptoms consistent with myelitis or radiculitis develop, diagnostic workup and treatment should be initiated according to the standard of care. Management may require interruption or discontinuation of QALSODY.
Papilledema and Elevated Intracranial Pressure
Serious adverse reactions of papilledema and elevated intracranial pressure have been reported in patients treated with QALSODY. Four patients developed elevated intracranial pressure and/or papilledema. All patients received treatment with standard of care with resolution of symptoms, and no events led to discontinuation of QALSODY. If symptoms consistent with papilledema or elevated intracranial pressure develop, diagnostic workup and treatment should be initiated according to the standard of care.
Aseptic Meningitis
Serious adverse reactions of aseptic meningitis (also called chemical meningitis or drug-induced aseptic meningitis) have been reported in patients treated with QALSODY. One patient experienced a serious adverse reaction of chemical meningitis, which led to discontinuation of QALSODY. One patient experienced a serious adverse reaction of aseptic meningitis, which did not lead to discontinuation of QALSODY. In addition, nonserious adverse drug reactions of CSF white blood cell increased, and CSF protein increased have also been reported with QALSODY. If symptoms consistent with aseptic meningitis develop, diagnostic workup and treatment should be initiated according to the standard of care.
Adverse events in VALOR1
The most common adverse reactions (≥ 10% of patients treated with QALSODY and greater than placebo) were pain, fatigue, arthralgia, CSF white blood cell increased, and myalgia.
Less Common Adverse Reactions
Serious adverse reactions of myelitis and radiculitis; papilledema and elevated intracranial pressure; and aseptic meningitis have occurred in patients treated with QALSODY.
In the long-term extension study, nonserious adverse reactions of pyrexia have occurred with repeat administration of QALSODY.
*Pain includes preferred terms of pain, back pain, and pain in extremity.
†CSF white blood cell increased includes preferred terms of CSF white blood cell increased and pleocytosis.
Dosing and administration
After an initial dosing period, QALSODY is administered
every 28 days1
QALSODY should be administered intrathecally using a lumbar puncture by healthcare professionals experienced in performing lumbar punctures.1
Missed second dose1:
If the second loading dose is missed, administer QALSODY as soon as possible, and give the third loading dose 14 days later.
Missed third dose1:
If the third loading dose is missed, administer QALSODY as soon as possible, and give the next dose 28 days later.
Missed maintenance dose1:
If a maintenance dose is missed, administer QALSODY as soon as possible, and give the next dose 28 days later.
Preparation instructions
Use aseptic technique when preparing and administering QALSODY intrathecally
Vial preparation
- Allow refrigerated QALSODY to warm to room temperature (25°C/77°F) prior to administration, without using external heat sources
- Inspect the solution in the QALSODY vial prior to administration. Do not administer if particles are observed or the liquid in the vial is not clear and colorless to slightly yellow
- Do not shake the vial
Procedural preparation
- If indicated by the clinical condition of the patient, consider sedation
- If indicated by the clinical condition of the patient, consider imaging to guide intrathecal administration of QALSODY
- Prior to removing the vial’s cap on the aluminum overseal, confirm readiness of the patient. An unopened QALSODY vial can be returned to the refrigerator
- Evaluate patients prior to and after intrathecal injection for the presence of potential conditions related to lumbar puncture, to avoid serious procedural complications
Overview of QALSODY intrathecal administration1
Please click for full Prescribing Information for complete preparation and administration details.
Storage and handling
Please click for full Prescribing Information for complete preparation, storage, and handling details.
