Tysabri (natalizumab) is an antibody-based therapy for multiple sclerosis (MS) that is used to reduce relapse rates, slow disability progression, and reduce the formation of new active brain lesions.
It was originally developed by Athena Neurosciences, and currently is owned and marketed by Biogen.
The central nervous system (CNS) — the brain and spinal cord — is surrounded by a cellular border called the blood-brain barrier. As its name suggests, this barrier regulates what substances are able to cross from the bloodstream into the CNS.
In MS, the immune system erroneously launches an inflammatory attack against myelin, the fatty molecule surrounding nerve fibers that is key for proper nerve cell communication. The immune cells that drive this attack must cross through the blood-brain barrier to get into the CNS and cause inflammatory damage.
This crossing is facilitated in part by the binding of the alpha-4-beta-1-integrin protein at the surface of immune cells to VCAM-1, a protein found on blood vessel cells.
Tysabri is an antibody that binds to alpha-4-beta-1-integrin and blocks its interaction with VCAM-1, thereby preventing the entry of immune cells into the brain and spinal cord. Ultimately, this reduces disease-driving inflammation in the CNS.
Tysabri was approved by the U.S. Food and Drug Administration (FDA) in 2004 to treat adults with relapsing forms of the disease, including clinically isolated syndrome (CIS), relapsing-remitting MS (RRMS), and active secondary progressive MS (SPMS).
The European Commission also approved Tysabri, in 2006, but only for the treatment of RRMS in adults with highly active disease. Other countries, such as Canada, Australia, and Brazil, have also approved the medication for people with RRMS.
According to Biogen, the therapy is available in more than 80 countries across the globe.
Taking Tysabri may increase a person’s risk of developing progressive multifocal leukoencephalopathy (PML), a rare brain infection that can be deadly or lead to severe disability. For this reason, the therapy is only available in the U.S. through a restricted distribution program called the TOUCH Prescribing Program. Many other countries also have requirements for monitoring patients on Tysabri.
Individuals with a PML infection, past or current, should not take Tysabri, and the treatment should be withheld immediately at the first sign or symptom suggestive of this infection.
Tysabri also is not recommended for patients who have experienced a life-threatening allergic reaction to natalizumab or any of the ingredients in the medication.
Tysabri is given via intravenous, or into-the-vein, infusions. It is administered at a 300 mg dose every four weeks. Each infusion takes about an hour, and patients must be observed for at least one hour after an infusion.
In the European Union, Tysabri also is available in pre-filled syringes for administration via subcutaneous (under-the-skin) injections. This formulation, however, was rejected by the FDA.
The international, placebo-controlled Phase 3 AFFIRM clinical trial (NCT00027300) evaluated the safety and effectiveness of Tysabri in adults with relapsing forms of MS. Participants were assigned randomly to receive Tysabri (627 patients) or a placebo (315 patients), every four weeks for more than two years.
Trial results showed that treatment with Tysabri significantly lowered the mean annualized relapse rate by 68% compared with a placebo. It also reduced the number of new or enlarging brain lesions by 83% relative to the placebo. The risk of sustained disability progression, defined as an increase in the Expanded Disability Status Scale (EDSS) score lasting at least three months, also was reduced by 42% over two years.
Another Phase 3 trial, called SENTINEL (NCT00030966), enrolled 1,171 people with RRMS who had experienced at least one relapse in the prior year while receiving treatment with Biogen’s Avonex (interferon beta-1a), another approved therapy. Participants in SENTINEL were given Tysabri or a placebo for up to 116 weeks (over two years), while continuing treatment with Avonex.
Adding Tysabri to Avonex treatment significantly reduced the risk of sustained disability progression, by 24%, compared with a placebo, results from SENTINEL showed. The combination treatment also reduced the mean annual relapse rate by 55%, and reduced the number of new or enlarging brain lesions on MRI scans by 83%.
Data from the AFFIRM and SENTINEL trials served as the basis for the FDA’s decision to approve Avonex in 2004.
The Biogen-sponsored, international REVEAL Phase 4 clinical trial (NCT02342704) and the BEST-MS observational study (NCT01981161) both compared the effectiveness of Tysabri against that of the approved MS therapy Gilenya (fingolimod), which also is available as a generic. Together, the studies involved more than 300 adults with RRMS.
Results from REVEAL showed that Tysabri reduced the mean number of new brain lesions with active inflammation to a greater degree than Gilenya after three months (by more than 70%), and that this difference was sustained through the trial’s six months. Tysabri treatment also resulted in a 92% lower risk of relapses over the duration of the study.
Data from the France-based BEST-MS study showed that a greater proportion of Tysabri-treated patients achieved no evidence of disease activity (NEDA) after one year of treatment, compared with those on Gilenya (47.8% vs. 30.4%). NEDA was defined as no relapses, no confirmed disability progression, and an absence of new or enlarging brain lesions. Patients receiving Tysabri also had significantly fewer relapses after six months of treatment — an annualized relapse rate of 0.02 vs. 0.09 for those on Gilenya — and were more likely to have no new brain lesions on MRI at one year (70% vs. 61.6%).
The Phase 1 DELIVER study (NCT00559702) and the Phase 2 REFINE trial (NCT01405820) both compared two different formulations of Tysabri: intravenous and subcutaneous. A total of 366 people with RRMS or SPMS were involved in the two trials. The two formulations were similar in their effectiveness, safety, and pharmacological properties, the results broadly highlighted.
A trial running through February 2023 is testing the safety and effectiveness of Tysabri when given every four weeks or every six weeks. Called NOVA (NCT03689972), the Phase 3b trial enrolled 499 RRMS patients across 97 study locations.
Participants had been on the standard Tysabri regimen, receiving infusions into the bloodstream every four weeks, for at least one year. They were then randomly assigned to continue with this approved treatment schedule, or to receive infusions every six weeks, for 72 weeks (about one year and four months).
NOVA clinical trial results broadly showed that both dosing schedules were comparable in terms of preventing relapses, disability progression, and brain lesions; safety data also were similar with both schedules.
The Biogen-sponsored Tysabri Observational Program (NCT00493298), dubbed TOP, is assessing the therapy’s long-term safety and effectiveness in 6,620 RRMS patients recruited at sites in Europe, Australia, Canada, and South America. It is the largest ongoing real-world study of Tysabri in RRMS, with participants being followed for up to 15 years. The study is expected to conclude in January 2029.
Both five-year and 10-year interim TOP data showed that Tysabri consistently reduced relapse rates and slowed disease progression, with patients showing stable EDSS scores for 10 years. No new safety concerns were identified with long-term treatment. A specific analysis of TOP’s 11-year results demonstrated that nearly one-quarter (23.9%) of patients achieved confirmed disability improvement (CDI), meaning less disability, during the study. Most (68.1%) of these patients maintained the CDI status over the duration of their follow-up.
The most common side effects associated with Tysabri in MS clinical trials include:
Tysabri carries a boxed warning for PML, a rare opportunistic brain infection that can be deadly. The risk of PML is highest in patients who:
Due to the increased risk of PML, Tysabri is only available in the U.S. through a restricted distribution program called TOUCH. Under this program, healthcare professionals, pharmacies, and infusion centers must be certified to prescribe, dispense, and infuse Tysabri.
Life-threatening and fatal herpes infections also have been reported in patients on Tysabri. In some patients, these infections can cause blindness. Tysabri should be stopped if patients show signs of these infections, and the infections should be treated appropriately.
Because Tysabri suppresses the immune system, the treatment also may increase the risk of other infections; thus, patients should be regularly monitored for signs of infection.
Tysabri may cause liver damage, which in some instances is severe enough to necessitate a liver transplant. The treatment should be stopped if patients show evidence of significant liver injury.
Some patients can experience a severe and potentially life-threatening allergic reaction in response to Tysabri. If such a reaction occurs, the treatment should be permanently discontinued, and appropriate supportive therapies should be given.
In some patients, the immune system mistakes the medicine for an infectious threat and produces anti-Tysabri antibodies. These antibodies, sometimes called “neutralizing” antibodies, can lower the efficacy of the medication, and also may increase the risk of allergic reactions or side effects during infusions. If neutralizing antibodies persist, patients and providers should discuss the potential risks and relative benefits of continued treatment.
While Tysabri has not been well-studied during pregnancy in people, animal data suggest that the medication can cause harm to a developing fetus. It also may cause low platelet levels and anemia in newborns exposed to Tysabri during pregnancy.
Tysabri can be detected in human milk, but the effects of this exposure on the nursing baby remain unknown.
It is recommended that patients and their healthcare providers discuss the potential risks and benefits, both for the patient and the baby, of continuing the therapy while pregnant or breastfeeding.
Multiple Sclerosis News Today is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.
Tysabri was approved in the U.S. in November 2004 to treat relapsing forms of multiple sclerosis — including clinically isolated syndrome, relapsing-remitting MS, and active secondary progressive MS. The U.S. Food and Drug Administration also approved Tysabri for patients with Crohn’s disease, a form of inflammatory bowel disease, in 2008.
According to Biogen, Tysabri begins to demonstrably reduce the risk of relapse as soon as two months after starting the therapy. Nonetheless, every person with MS is unique, and patients are advised to discuss with their healthcare team how the medication may help in their specific case.
Based on animal data, Tysabri may cause harm to a developing fetus. Therefore, the medication should only be used during pregnancy if the potential benefits of treatment justify the potential risk to the unborn child. Those who become or plan to become pregnant while on Tysabri should discuss the potential benefits and risks with their healthcare providers as early as possible.
Tysabri is not known to interact with alcohol. Nonetheless, since alcohol can interfere with some medications and worsen certain MS symptoms, patients should discuss safe alcohol consumption with their healthcare provider.
It is possible that patients on Tysabri may experience changes in body weight. In a clinical trial called AFFIRM, about 2% of patients given Tysabri experienced an increase in body weight, and a similar percentage had a decrease in body weight. Hair loss, however, was not reported as a side effect of Tysabri in clinical trials. Patients who experience any unexpected weight changes or unexplained hair loss should talk to their healthcare providers.
Get regular updates to your inbox.