Lemtrada (alemtuzumab) for multiple sclerosis

 

What is Lemtrada for MS?

Lemtrada (alemtuzumab) is an approved antibody-based therapy for relapsing forms of multiple sclerosis (MS) used to reduce relapses and prevent disability progression.

The therapy was originally developed by Genzyme, which was acquired by Sanofi in 2011.

Therapy Snapshot

Brand name:	Lemtrada
Chemical name:	Alemtuzumab
Usage:	Disease-modifying therapy for relapsing forms of MS
Administration:	Intravenous infusions

 

How does Lemtrada work?

MS is caused by the immune system erroneously attacking healthy parts of the central nervous system, which includes the brain, spinal cord, and optic nerves.

This inflammatory attack is driven by the actions of several types of immune cells. Two specifically, called B-cells and T-cells, are among the most powerful drivers of MS-causing autoimmunity.

The active agent in Lemtrada is an antibody that targets CD52, a protein found on the surface of B-cells and T-cells that has been implicated in their activation and migration. Treatment with Lemtrada, which attaches to this protein, leads to a rapid decrease in the levels of these cells, which is thought to reduce MS-associated inflammation.

Who can take Lemtrada?

The U.S. Food and Drug Administration (FDA) approved Lemtrada in 2014 for the treatment of adults with relapsing forms of MS, including relapsing-remitting MS (RRMS) and active secondary progressive MS (SPMS).

But because Lemtrada can increase the risk of severe complications, such as autoimmune conditions, infusion reactions, and cancer, it is generally recommended in the U.S. for patients who have failed to respond to at least two other MS treatments.

In the U.S., the medication is available only through a restricted distribution program called Lemtrada REMS — Risk Evaluation and Mitigation Strategy. This program ensures that healthcare professionals, pharmacies, and infusion centers are certified to prescribe, dispense, and infuse Lemtrada.

In the EU, the European Commission approved Lemtrada in 2013 for adults with RRMS and highly active disease, as defined by certain clinical or imaging features. In countries such as Australia and Canada, Lemtrada also is available for people with active RRMS.

In all, Lemtrada is approved in more than 60 countries to treat adults with relapsing forms of MS, according to Sanofi Genzyme.

Most of these countries also have a number of restrictions in place for the therapy’s use, including training for healthcare professionals dealing with the medication and additional monitoring for patients.

Who should not take Lemtrada?

Due to its safety profile, Lemtrada is not recommended for use in people with clinically isolated syndrome (CIS) — those who experienced a first episode of neurological symptoms similar to those of MS but have not been diagnosed with overt disease.

It also should not be administered to individuals with:

• a human immunodeficiency virus (HIV) infection
• an active infection
• known allergies to alemtuzumab or any other component in the medication

How is Lemtrada administered?

Lemtrada is delivered via intravenous (into-the-bloodstream) infusions, each lasting about four hours. These infusions are given by a certified professional at a daily dose of 12 mg in two courses of treatment. These include:

• a first course of 60 mg total dose, including five infusions on five consecutive days
• a second course of 36 mg total dose, involving three infusions on three consecutive days, one year after the first course

In each subsequent year, patients may need an additional round of infusions for three consecutive days (36 mg in total). They must be given at least one year after the last treatment course.

Before each infusion, patients are premedicated with anti-inflammatory corticosteroids, as well as antihistamines or anti-fever medication, to prevent serious infusion reactions. Patients also will start on antivirals on the first day of each treatment course and continue on them for at least two months after the last infusion.

After each Lemtrada infusion, patients are monitored for allergic reactions or serious infusion reactions for about two more hours. The total appointment time for each infusion is up to eight hours.

Administration	Intravenous infusions
Dosage	Daily dose of 12 mg; first course of 60 mg total dose; second course of 36 mg total dose
Timing	For first course, five infusions for five consecutive days; for second course, three infusions on three consecutive days, one year after the first course

 

Lemtrada in clinical trials

After an initial trial in SPMS patients suggested that Lemtrada should be given earlier in the disease course, Genzyme began testing the therapy in people with RRMS.

CAMMS223 trial

The CAMMS223 Phase 2 trial (NCT00050778) enrolled 334 people with early RRMS and active disease. Participants were randomly assigned to receive one of two doses of Lemtrada (12 mg or 24 mg), or Rebif (interferon beta-1a), an older approved MS treatment, over three years. The Lemtrada was given via intravenous infusions in three annual courses, while Rebif was administered under the skin (subcutaneously) three times per week.

Compared with Rebif, the 12 mg dose of Lemtrada significantly reduced annualized relapse rates by about 69%. It also lowered the proportion of patients who experienced sustained disability accumulation by 75% in comparison with Rebif. Those treated with Lemtrada also experienced smaller changes in brain volume over the three years.

Lemtrada dosing was stopped, almost three years after the trial started, due to reports of patients developing a blood-clotting disorder, which was fatal in one case. Patients on Rebif, however, continued on their planned treatment until the end of the trial.

Notably, an analysis done after the trial was complete showed that more patients treated with Lemtrada remained free of clinical disease activity, defined as no relapses or sustained disability worsening, for the three-year trial duration (72% vs. 43%).

CARE-MS trials

The approvals of Lemtrada were based on two pivotal Phase 3 studies. These trials compared the benefits of Lemtrada versus Rebif in patients with active RRMS who were either new to treatment  (CARE-MS 1) or who had relapsed while on prior therapy (CARE-MS 2).

CARE-MS 1 (NCT00530348) enrolled 581 patients with relatively mild disease who were within five years of their diagnosis and had not been previously treated. CARE-MS 2 (NCT00548405) involved 840 patients who had experienced at least one relapse while on another prior MS therapy and who had been diagnosed in the past 10 years. In both studies, treatment was continued for up to two years.

Results from the CARE-MS trials generally were consistent with the earlier Phase 2 data.

Treatment with Lemtrada in both trials significantly reduced the annual relapse rate by about 50% compared with Rebif — 0.18 vs. 0.39 relapses per year in CARE-MS 1, and 0.26 vs. 0.52 relapses per year in CARE-MS 2. It also lowered a number of measures of brain damage in MRI scans. These included the development of new or enlarging brain lesions, the number of lesions with active inflammation, and the loss of brain volume.

However, the risk of six-month sustained disability progression over the trials’ two-year spans was only significantly reduced by Lemtrada in CARE-MS2 — by about 42%. No significant differences in disability progression were observed between the two treatment groups in CARE-MS1. That was mostly attributed to a lower-than-expected rate of progression among patients given Rebif.

Open-label extension trial

Participants who completed the CAMMS223 or CARE-MS trials had the option to enroll in an open-label extension trial (NCT00930553), in which all were treated with Lemtrada as needed (as long as treatment courses were at least 12 months apart) and monitored for safety and efficacy for four years.

Most participants did not require more Lemtrada courses or any additional treatments, and about 80% had disability that was either stable or improved, trial results showed. Relapse rates were also sustained at low levels over the years.

Further data from the studies and the extension suggested that Lemtrada treatment reduced the risk of conversion from RRMS to SPMS.

Ongoing trials

Sanofi is currently running LemKids, an open-label Phase 3 trial (NCT03368664) designed to assess Lemtrada’s safety and efficacy in pediatric patients. This trial involves about 50 children and adolescents, ages 10 to 17, with RRMS. Participants must have failed to successfully respond to at least one disease-modifying therapy prior to the trial.

The primary goal is to evaluate if Lemtrada reduces the number of new or enlarging brain lesions compared with the children’s previous therapy. Researchers also will investigate changes in disability status, relapse rate, cognition, and quality of life. The study is expected to be completed in December 2025.

Common side effects of Lemtrada

The most common side effects of Lemtrada in MS clinical trials were:

• rash
• headache
• fever
• the common cold
• flushing
• urinary tract infection
• nausea and vomiting
• fatigue
• insomnia
• infection in the upper respiratory tract
• herpes virus infection
• welts (urticaria)
• itching
• thyroid diseases
• fungal infections
• diarrhea
• sinus inflammation
• dizziness
• burning or prickling sensation (paresthesia)
• pain in the joints, extremities, back, throat, and/or abdomen

Other concerns regarding the use of this medication that may have more severe consequences include a possible increased risk of autoimmune diseases and infusion reactions. The therapy carries additional warnings on its label for possible stroke or cancer.

Autoimmune disorders

Lemtrada can lead to the formation of autoantibodies, and increase the risk of serious autoimmune conditions, such as:

• immune thrombocytopenia, characterized by easy bruising and bleeding
• other autoimmune disorders causing low counts of certain blood cells
• anti-glomerular basement membrane disease, which affects the kidneys and lungs
• thyroid disorders, including Graves’ disease or autoimmune thyroiditis
• other autoimmune disorders causing low blood cell counts
• autoimmune hepatitis that may cause significant damage to the liver
• acquired hemophilia A, a bleeding disorder

Blood counts and markers of kidney health should be regularly monitored up to four years after the last dose of the therapy. Measures of thyroid and liver function also should be assessed regularly during and for several years after treatment.

Infusion site reactions

Lemtrada can cause infusion reactions, which are common in most patients, and sometimes occur more than a day after the infusion.  Reactions that are serious or life-threatening can occur. Due to these risks, Lemtrada must be administered in a setting where there is equipment and personnel to closely monitor patients and manage any reactions during and after infusions.

Cardiovascular problems

Some people on Lemtrada experienced serious and sometimes fatal cardiovascular problems, such as stroke or tears in their carotid or vertebral arteries. These arteries are major blood vessels in the neck, and these issues occurred within three days of receiving the medication. Patients should seek immediate medical care if symptoms of heart conditions occur.

Cancer

Treatment with Lemtrada may increase the risk of certain cancers, including thyroid cancer, melanoma (a type of skin cancer), and blood cancers, such as lymphoma or lymphoproliferative disorders. Patients should be monitored before and during treatment for these types of cancers, and receive annual skin exams.

Infections and vaccines

Because Lemtrada affects the immune system, it may increase the risk of serious infections, including the bacterial infection listeria, herpes viral infections, tuberculosis, and hepatitis. Patients also can develop a viral brain infection called progressive multifocal leukoencephalopathy (PML), which usually leads to severe disability or death. If any infections are suspected, patients should seek immediate medical care.

Vaccines that contain a live virus are not recommended during Lemtrada treatment, as patients are at increased risk of infection following their administration.

Inflammatory conditions

The medication may increase the risk of an overactive immune system, leading to conditions such as:

• hemophagocytic lymphohistiocytosis, a severe systemic inflammatory syndrome in which the immune system attacks other blood cells, causing damage to the spleen and liver
• adult-onset Still’s disease, a rare type of inflammatory arthritis that causes fever, joint pain, and rash

Clotting problems

The development of antibodies due to Lemtrada treatment also can result in a blood-clotting condition called thrombotic thrombocytopenic purpura. If signs of this condition develop, treatment should be stopped.

Use in pregnancy and breastfeeding

Lemtrada has not been well-studied during pregnancy in humans, but research in animals suggests it may cause harm to a developing fetus. Pregnant patients with untreated thyroid disorders caused by Lemtrada also have an increased risk of miscarriage.

It is generally recommended that people of childbearing age use effective birth control methods while receiving the medication and for at least four months following each course of treatment.

Research in animal models has found traces of Lemtrada in breast milk. Those who plan to breastfeed should inform their healthcare team and carefully weigh the potential benefits and risks of using the medication while nursing.

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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.