Seven months after starting a safety review of Lemtrada (alemtuzumab), the Pharmacovigilance Risk Assessment Committee (PRAC) that oversees the safety of medicines approved in the European Union has issued final recommendations to minimize the risk of serious side effects linked to its use in relapsing-remitting multiple sclerosis (MS).

Concerns were based on reports of rare but serious complications associated with Lemtrada, including deaths related to immune complications and heart or circulatory disorders.

Specifically, reports of fatalities and severe effects were associated with immune complications that included autoimmune hepatitis (immune-caused liver damage) and hemophagocytic lymphohistiocytosis (a disorder that may affect several organs in the body), and hemolytic anemia (abnormal red cell breakdown). Some immune reactions could happen “many months” after treatment with Lemtrada, PRAC noted.

Reports also surfaced of severe and deadly heart, circulation, and bleeding disorders, including heart attack, stroke, bleeding in the lungs, and cervicocephalic arterial dissection (tears in the arteries from the head and neck). These adverse events, PRAC said, could develop within days of Lemtrada’s use.

While PRAC’s review was underway, the committee — an arm of the European Medicines Agency (EMA) — issued preventative measures restricting the use of Lemtrada (marketed by Sanofi Genzyme) to adult RRMS patients who failed prior treatments, or were ineligible for other disease-modifying therapies (DMTs).

The newly published recommendations replace those earlier measures.

PRAC now advises that Lemtrada use be restricted to:

adults with RRMS who have “highly active disease despite adequate treatment” with at least one other DMT.

adults with RRMS and rapid disease worsening, defined as at least two disabling relapses in a year and new brain lesions seen on MRI (magnetic resonance imaging) scans.

Treatment with this vein infusion (drip) medicine take place only in hospitals with “ready access to intensive care facilities (ICUs) and specialists who can manage serious adverse reactions.”

PRAC also recommends that Lemtrada:

can no longer be used by patients with certain heart, circulation or bleeding disorders.

can no longer be given to RRMS patients with other autoimmune disorders.

The physician’s guide and the patient information that accompanies Lemtrada should also be updated to alert all that serious side effects can occur shortly or many months after a Lemtrada infusion, PRAC said.

These final recommendations will now be reviewed by EMA’s Human Medicines Committee (CHMP), which will issue an opinion. Based on that opinion, the European Commission will make a final decision that will apply to all EU member states.

Lemtrada is a humanized monoclonal antibody used to delay disease progression in adults with RRMS. It works by inhibiting CD52, a protein found on the surface of immune B- and T- cells. By doing so, it inactivates these cells to slow the neuroinflammation associated with MS.

To date, Lemtrada is an approved MS treatment in more than 30 countries; its approval in the European Union came in 2013, and the U.S. in 2014.