Biogen has initiated a phase 3 clinical trial evaluating tofersen (previously called BIIB067), an antisense oligonucleotide (ASO), a type of antisense drug, targeting superoxide dismutase (SOD1), for the potential treatment of ALS. The trial is now enrolling and aims to enroll approximately 60 people with SOD1 ALS.
At this week’s 2019 American Academy of Neurology (AAN) Annual Meeting in Philadelphia, Biogen presented promising results of their phase 1/2 SOD1-ALS trial (tofersen – BIIB067). They were encouraged by the initial findings of the study, so they are moving into a larger phase 3 trial to further test the safety and efficacy of tofersen. While this news is promising, it is important to note that the drug (tofersen) is still experimental.
Approximately two percent of people living with ALS have a mutation in the SOD1 gene, which is the second most common cause of genetic ALS. The SOD1 mutation leads to abnormal protein, which is likely toxic to cells and could lead to the death of motor neurons, the cells that die in ALS.
Tofersen is designed to reduce levels of SOD1 protein in people with ALS caused by a SOD1 gene mutation. The goal is to offer a therapeutic benefit for people living with ALS that carry SOD1 gene mutations.
Below is an FAQ about tofersen and the VALOR trial, including more information about how to enroll.
Amyotrophic Lateral Sclerosis (ALS) and confirmed Superoxide Dismutase 1 (SOD-1) Mutation
- Study name
A Study to Evaluate the Efficacy, Safety, Tolerability, Pharmacokinetics and Pharmacodynamic Study of BIIB067 in Adults with Inherited Amyotrophic Lateral Sclerosis (ALS) and Confirmed Superoxide Dismutase 1 Mutation
- Study coordinator name and contact information to learn more about the trial
US Biogen Clinical Trial Center (866) 633-4636; [email protected]
- Endpoint Classification
Safety, efficacy, pharmacokinetics (PK) (how the drug behaves in the body, such as how it is absorbed, distributed, metabolized, and excreted), and pharmacodynamics (PD) (what the drug does to the body, such as biochemical, physiological, and molecular effects in the body).
- Trial Primary Endpoint
The trial primary endpoint is the ALS Functional Rating Scale – Revised (ALSFRS-R). Other endpoints include: Incidence of Adverse Events and Serious Adverse Events, Incidence of abnormalities in clinical laboratory assessments, vital signs, physical and neurological examinations, and electrocardiograms, PK measures, including plasma and cerebrospinal fluid levels of BIIB067.
- Study design
This is a fixed-dose design with subjects randomized to the investigational drug or placebo. Masking is Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor).
- In layman’s terms, what is the hypothesized biologic effect of the drug?
Researchers believe that a reduction of the SOD1 protein may offer a therapeutic benefit for people with ALS caused by a SOD1 gene mutation. Tofersen is an antisense oligonucleotide (ASO), which is designed to reduce levels of SOD1 protein in people with ALS caused by a SOD1 gene mutation (SOD1-ALS).
- What is the eligibility criteria?
Study participants must:
- Be 18 years of age or older
- Have weakness caused by ALS
- Agree to genetic testing for the SOD1 mutation
For more information on inclusion and exclusion criteria, visit: https://clinicaltrials.gov/ct2/show/NCT02623699
- What is the length of required participation for each participant?
For participants taking part in phase 3, the study duration will be approximately 32 weeks
- What is the number and frequency of doctor visits?
(Up to 2 Visits, Up to 4 Weeks)
To participate in this study, you must have confirmation of a SOD1 gene mutation. If you do not have documentation of your SOD1 gene mutation, you will be asked to provide a blood sample for genetic testing to confirm that you have a mutation in your SOD1 gene. Other tests and assessments will be performed to make sure the study is a good match.
Study Treatment Period
(Up to 8 Visits, Up to 24 Weeks)
You will be assigned to a study drug group at random (by chance) to receive either the investigational drug or placebo. You will have a 2-in-3 chance of being assigned to the investigational drug group, and a 1-in-3 chance of being assigned to the placebo group.
You will receive a dose of the study drug (or placebo) as described earlier and you will receive this dose 8 times. After you receive the first dose of the study drug (Day 1), you will then return to the study center, to receive 7 more doses of study drug on or around Days 15, 29, 57, 85, 113, 141, and 169 (the first 3 doses every 2 weeks and the 5 remaining doses approximately once every 4 weeks).
(1 visit, 4 Weeks After Last Dose)
You will return to the study location for some final tests and assessments.
At the follow-up visit, if study participants are eligible and interested, they may have the option to enter an open-label extension study, where all trial participants will receive tofersen for an extended period of time.
- Will the drug be available via expanded access?
The data for tofersen to date is supportive of continued research, but it does not demonstrate whether it is safe or effective. Biogen is working quickly and efficiently to understand the benefit/risk profile of tofersen and to understand potential regulatory pathways. As an investigational therapy, tofersen is currently only available through clinical trials.
Currently, there is no expanded-access program or single-patient access/compassionate use available for tofersen.
- What is the delivery method?
The investigational drug or placebo is delivered intrathecally. Intrathecally means that the study drug is given to you by a procedure called a lumbar puncture
- How does a lumbar puncture procedure work?
Before the investigational drug or placebo is given, a trained clinician will perform a lumbar puncture (LP). During the LP, the clinician puts a thin needle into the fluid-filled space below the end of your spinal cord through the lower back. The clinician will take a sample of your cerebrospinal fluid and then inject the study drug.
- What are the tests/outcome measures at each visit?
Study participant assessments and activities will vary from visit to visit but may include:
- Carefully Review and Sign the Informed Consent Form
- Review Eligibility Criteria
- Collect Medical History
- Randomization to Study Group
- Vital Signs
- Physical Exam
- Neurological Exam
- Electrocardiogram (ECG)
- Blood Tests
- Urine Tests
- Pregnancy Test*
- Lumbar Puncture (LP)
- ALS Scales and Assessments
- Receive the Investigational Drug or Placebo
*For women of childbearing potential
- What clinical trial sites are enrolling?
For more information about clinical trial site locations, visit https://www.neals.org/als-trials/5590 or https://clinicaltrials.gov/ct2/show/NCT02623699.