The National Institute for Health and Care Excellence (NICE) has recommended natalizumab for treating adults with highly active relapsing-remitting multiple sclerosis (RRMS) whose disease has responded inadequately to previous disease-modifying therapy (DMT). 

Under NICE’s final draft guidance, use is contingent on two criteria: Cladribine must be unsuitable for the patient's disease characteristics and activity, and companies must maintain agreed pricing through the Medicines Procurement and Supply Chain framework.

The recommendation applies to two formulations of natalizumab: Tysabri, the originator drug from Biogen, administered as a subcutaneous (SC) injection, and Tyruko, a biosimilar from Sandoz, given by intravenous (IV) infusion.

NICE excluded the IV formulation of natalizumab, concluding it does not represent acceptable value for NHS resources in this patient population. 

NICE said the recommendation could benefit thousands of people with highly active RRMS, including those planning pregnancy, because natalizumab can be continued during pregnancy, unlike several other high-efficacy DMTs. 

Ceri Smith, head of policy at the MS Society, called natalizumab a “highly effective treatment” and said the decision will “particularly benefit people who want to start a family.”

Disease Background and Eligible Patients

Multiple sclerosis affects approximately 123,000 people in the UK and occurs three times more frequently in women than men. An estimated 43,000 people are living with RRMS at any given time.

The condition develops when immune cells mistakenly attack myelin, the protective covering around nerves. This can lead to progressive and irreversible disability. Symptoms include pain, chronic fatigue, unsteady gait, muscle loss, speech problems, incontinence, visual disturbance, and cognitive impairment. Most patients experience the relapsing-remitting form of the disease, characterised by periods of new or worsened symptoms.

“Highly active” RRMS describes disease that continues to cause relapses or show signs of activity despite completion of a full course of DMT. Current treatment options after first-line therapy include ocrelizumab, ofatumumab, ublituximab, and cladribine. Natalizumab offers advantages for patients at high risk for additional relapses, such as those with large lesion loads or enhancing lesions visible on imaging.

Drug Mechanism and Clinical Evidence

Natalizumab is a monoclonal antibody that is categorised as an integrin inhibitor and is used as a DMT in RRMS. It works by binding to immune system T and B cells, preventing them from entering the brain and spinal cord where they would otherwise damage myelin.

The drug is administered every 4 weeks, either as a hospital infusion or SC injection. 

Natalizumab is associated with an increased risk for progressive multifocal leukoencephalopathy (PML), a potentially fatal brain condition caused by John Cunningham human polyomavirus (JCV). Risk factors include the presence of anti-JCV antibodies, treatment duration beyond 2 years, and previous immunosuppressant use. Patients require regular anti-JCV antibody testing before and during treatment.

Clinical trial evidence demonstrated that natalizumab originator reduces relapse rates compared with placebo. The biosimilar is expected to have equivalent efficacy and safety.

Pivotal and supportive data include:

• AFFIRM (n = 1618; 2 years): 42% reduction in disability progression (hazard ratio [HR], 0.58) and an 83% reduction in new lesion accumulation vs placebo
• ANTELOPE (n = 264; 24 weeks): biosimilar demonstrated equivalent efficacy to originator (mean new lesions, 0.34 vs 0.45; no significant difference)
• REVEAL (n = 108; 24-36 weeks): superiority over fingolimod, with a 92% relapse reduction (HR, 0.08) and 77% fewer new lesions
• A Japanese study (n = 149; 24 weeks): 83% reduction in new lesions and 69% lower annualised relapse rate vs placebo (0.53 vs 1.73) 

Pricing and Implementation

The list price for Tysabri is £1130 per 300-mg dose for both IV and SC formulations. Tyruko is priced at £1017 per 300-mg IV dose.

Both manufacturers have agreed nationally available price reductions via the Medicines Procurement and Supply Chain framework. The discounted prices are confidential.

Standard dosing is 300 mg every 4 weeks. Extended-interval dosing every 6 weeks is widely used in clinical practice, affecting approximately 60%-70% of patients, to reduce PML risk in anti-JCV-positive patients.

The recommendation aligns with NICE’s support for biosimilar adoption to expand access and improve NHS value. NHS England will be required to fund the endorsed formulations within 90 days of publication of the final guidance for eligible patients.

The decision reflects NICE’s life-cycle approach to reassessing medicines as more affordable options become available.