Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Label indication QALSODY is indicated for the treatment of amyotrophic lateral sclerosis (ALS) in adults who have a mutation in the superoxide dismutase 1 ( SOD1 ) gene. This indication is approved under accelerated approval based on reduction in plasma neurofilament light chain (NfL) observed in patients treated with QALSODY [see Clinical Studies ( 14 )] . FDA label
Also known as BIIB067, QALSODY
Tofersen · 4 trials · 4 indications
An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. An SAE is any untoward medical occurrence that at any dose results in death, life-threatening event, requires inpatient hospitalization, significant disability/incapacity or congenital anomaly. TEAEs were defined as any AEs or SAE with an onset date and time that was on or after the first dose of study drug, or any pre-existing condition that worsened in severity after the first dose of study drug.
An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. A SAE is any untoward medical occurrence that at any dose results in death, life-threatening event, requires inpatient hospitalization, significant disability/incapacity or congenital anomaly.
Clinical laboratory assessments included hematology, chemistry, and urinalysis.
The criteria for clinically significant vital sign abnormalities include: Temperature: \>38 degree Celsius (°C) or an increase from baseline of ≥1°C; Pulse: \>120 beats per minute (bpm) or an increase from baseline of \>20 bpm, \<50 bpm or a decrease from baseline of \>20 bpm; Systolic blood pressure (BP): \>180 mmHg or an increase from baseline of \>40 mmHg, \<90 mmHg or a decrease from baseline of \>30 mmHg; Diastolic BP: \>105 mmHg or an increase from baseline of \>30 mmHg, \<50 mmHg or a decrease from baseline of \>20 mmHg.
Clinically significant physical examination abnormalities included weight decreased.
Clinically significant neurological examination abnormalities included hyporeflexia.
The ALSFRS-R measures 4 functional domains, including respiratory, bulbar function, gross motor skills, and fine motor skills. There are 12 questions, each scored from 0 (no function) to 4 (full function), for a total possible score of 48. Scores decline with disease progression. ALSFRS-R scores calculated at diagnosis can be compared to scores throughout time to determine the speed of progression. Higher scores represent better function, negative change from baseline indicates disease progression.
| Arm | Type | Description |
|---|---|---|
| Part A: Natural History Run-in | NO_INTERVENTION | Participants enrolled in Part A will undergo blood draws approximately once every 28 days to assess NfL levels. |
| Part B: Randomized, Double-Blind, Placebo-Controlled | EXPERIMENTAL | Participants from Part A who meet the protocol-defined NfL threshold and remain presymptomatic may be eligible to participate in Part B. During Part B, participants will receive tofersen 100 milligrams (mg) or placebo via IT injection on Days 1, 15, 29, and every 28 days thereafter for up to approximately 5.6 years. |
| Part C: Open-Label Extension | EXPERIMENTAL | Participants from Part B who develop clinically manifest ALS may be eligible to participate in Part C. During Part C, participants who received placebo in Part B will receive tofersen 100 mg via IT injection on Days 1, 15, 29, and every 28 days thereafter up to the final maintenance dose visit. Participants who received tofersen during Part B will receive tofersen 100 mg on Days 1, 29, and every 28 days thereafter up to the final maintenance dose visit, with a dose of placebo on Day 15 to maintain the study blind. The combined duration of Part B and Part C is up to approximately 5.6 years. |
| Part D: Open-Label Treatment | EXPERIMENTAL | Participants from Part A who develop clinically manifest ALS prior to randomization in Part B may be eligible to participate in Part D. During Part D, participants will receive tofersen 100 mg via IT injection on Days 1, 15, 29, and every 28 days thereafter for up to 2 years. |
| BIIB067 | EXPERIMENTAL | Participants who have completed Parts A, B, or C of study 233AS101 will be placed in this arm. |
| Part A-SAD: Combined Placebo | PLACEBO_COMPARATOR | Participants will be administered tofersen-matching placebo once by intrathecal bolus injection on Day 1 of Cohorts 1, 2, 3, and 4 respectively. |
| Part A-SAD: Cohort 1: Tofersen 10 mg | EXPERIMENTAL | Participants will be administered tofersen 10 mg once by intrathecal bolus injection on Day 1. |
| Part A-SAD: Cohort 2: Tofersen 20 mg | EXPERIMENTAL | Participants will be administered tofersen 20 mg once by intrathecal bolus injection on Day 1 of Cohort 2 after the safety review of Cohort 1. |
| Part A-SAD: Cohort 3: Tofersen 40 mg | EXPERIMENTAL | Participants will be administered tofersen 40 mg once by intrathecal bolus injection on Day 1 of Cohort 3 after the safety review of Cohort 2. |
| Part A-SAD: Cohort 4: Tofersen 60 mg | EXPERIMENTAL | Participants will be administered tofersen 60 mg once by intrathecal bolus injection on Day 1 of Cohort 4 after the safety review of Cohort 3. |
| Part B-MAD: Combined Placebo | PLACEBO_COMPARATOR | Participants will be administered tofersen-matching placebo, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection. |
| Part B-MAD: Cohort 5: Tofersen 20 mg | EXPERIMENTAL | Participants will be administered tofersen 20 mg, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection. |
| Part B-MAD: Cohort 6: Tofersen 40 mg | EXPERIMENTAL | Participants will be administered tofersen 40 mg, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection after the safety and PK review of Cohort 5. |
| Part B-MAD: Cohort 7: Tofersen 60 mg | EXPERIMENTAL | Participants will be administered tofersen 60 mg, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection after the safety, PK review and SOD1 PD review of Cohort 6. |
| Part B-MAD: Cohort 8: Tofersen 100 mg | EXPERIMENTAL | Participants will be administered tofersen 100 mg, 3 loading doses once every 2 weeks on Days 1, 15, 29 and 2 maintenance doses once every 4 weeks on Days 57 and 85 by intrathecal injection after the safety, PK review and SOD1 PD review of Cohort 7. |
| Part C-Pivotal: Placebo | PLACEBO_COMPARATOR | Participants will be administered tofersen-matching placebo, 3 loading doses administered once every 2 weeks on Days 1, 15, 29 followed by 5 maintenance doses administered once every 4 weeks on Days 57, 85, 113, 141, 169 up to 24 weeks by intrathecal bolus injection. |
| Part C-Pivotal: Tofersen 100 mg | EXPERIMENTAL | Participants will be administered tofersen 100 mg, 3 loading doses administered once every 2 weeks on Days 1, 15, 29 followed by 5 maintenance doses administered once every 4 weeks on Days 57, 85, 113, 141, 169 up to 24 weeks by intrathecal bolus injection. |
| Tofersen | EXPERIMENTAL | - |
| Name | Type | Description |
|---|---|---|
| Tofersen | DRUG | Administered as specified in the treatment arm |
| Placebo | DRUG | Administered as specified in the treatment arm |
Key Part A Inclusion Criteria: * Participants should have a protocol-defined rapidly progressive SOD1 mutation, confirmed by a central reader, or a SOD1 mutation that is approved for inclusion by an external mutation adjudication committee. * Participants with plasma NfL level less than the protoco...
Tofersen is an investigational RNA therapy being developed for amyotrophic lateral sclerosis (ALS), including ALS associated with a SOD1 gene mutation. It is also being studied in people with ALS who do not carry a SOD1 mutation. Tofersen is in clinical development and has not been established as an approved treatment.
Tofersen targets SOD1, the superoxide dismutase 1 gene product, and is designed as an antisense inhibitor. By acting on SOD1, the RNA therapy aims to reduce production of the SOD1 protein in people with ALS linked to SOD1 mutations. It is given as an RNA-based therapy in the neurology field.
Tofersen is being developed by Biogen Inc., which trades under the ticker BIIB. Biogen is the sponsor behind the clinical trial program for tofersen in ALS, including studies in SOD1 mutation carriers and in non-SOD1 ALS. The drug is also referred to in trial records as BIIB067.
Tofersen is in Phase 2 and Phase 3 clinical development for ALS. Its trial program includes a recruiting Phase 2 study in non-SOD1 ALS and Phase 3 studies in SOD1-associated ALS, one of which is active and not recruiting. Tofersen has received a priority review designation from the FDA.
Tofersen trials include NCT07294144, a recruiting Phase 2 study in non-SOD1 ALS enrolling 30 participants in the United States. Phase 3 studies include NCT04856982 in presymptomatic SOD1 mutation carriers, NCT03070119, a completed long-term evaluation, and NCT02623699, a completed Phase 3 study enrolling 176 adults with inherited ALS.
Yes, tofersen is also known as BIIB067. Trial records list the investigational drug under both names, including the Phase 3 study of BIIB067 (tofersen) in adults with inherited ALS and the long-term evaluation of BIIB067 (Tofersen). Readers searching either name are looking at the same Biogen ALS candidate.