Ofatumumab

Multiple Sclerosis

Ofatumumab is used to treat adults with relapsing forms of multiple sclerosis (MS). This includes the following conditions:

• Clinically isolated syndrome: This is a first episode of neurologic symptoms that lasts at least 24 hours and may be the earliest sign of MS.
• Relapsing-remitting disease: This is a form of MS characterized by clearly defined attacks of new or increasing neurologic symptoms, followed by periods of partial or complete recovery.
• Active secondary progressive disease: This is a stage of MS that follows a relapsing-remitting course, where the disease continues to worsen with recognizable relapses.

Chronic Lymphocytic Leukemia

Ofatumumab is also used to treat adults with chronic lymphocytic leukemia (CLL), a type of cancer that affects the blood and bone marrow. It may be prescribed in several situations:

• As a first-line treatment for patients who have not previously received medication for CLL.
• For patients whose cancer has returned or progressed after previous treatments.
• As a maintenance therapy for patients who have responded to at least two previous treatments, to help delay the cancer's return.
• For patients whose CLL no longer responds to specific types of chemotherapy.

Targeting B Cells

Ofatumumab is a type of medication known as a monoclonal antibody. These are laboratory-made proteins designed to recognize and bind to specific targets in the body. Ofatumumab specifically targets a protein called CD20, which is found on the surface of B-lymphocytes (B cells), a type of white blood cell.

Mechanism of Action

When ofatumumab attaches to the CD20 protein on a B cell, it triggers the body's immune system to attack and destroy that cell. This process helps manage conditions where B cells are either cancerous or overactive:

• Multiple Sclerosis (MS): In relapsing forms of MS, the immune system mistakenly attacks the protective coating of nerves. By reducing the number of B cells, ofatumumab helps prevent this immune-mediated damage.
• Chronic Lymphocytic Leukemia (CLL): In this type of cancer, the body produces too many abnormal B cells. Ofatumumab works by binding to these cancerous cells so the immune system can eliminate them from the blood and bone marrow.

By lowering the levels of these specific cells, the medication helps reduce inflammation in MS and slows the progression of cancer in CLL.

Common Side Effects

Many people using ofatumumab experience mild to moderate side effects. These often include:

• Injection site reactions: Redness, pain, itching, or swelling where the medicine was injected.
• Infections: Upper respiratory tract infections, such as the common cold, sore throat, or sinus pressure.
• Systemic reactions: Fever, headache, muscle aches, and tiredness, particularly after the first dose.
• Digestive issues: Nausea or diarrhea.

Serious Side Effects

While less common, ofatumumab can cause serious health problems. Seek medical attention immediately if you experience:

• Severe infusion or injection reactions: Symptoms may include shortness of breath, chest pain, wheezing, rash, or swelling of the face and tongue.
• Serious infections: Increased risk of pneumonia, urinary tract infections, or other bacterial and viral infections.
• Hepatitis B reactivation: If you have had hepatitis B in the past, the virus can become active again.
• Progressive Multifocal Leukoencephalopathy (PML): A rare but life-threatening brain infection. Symptoms include confusion, dizziness, loss of balance, or vision changes.
• Low immunoglobulin levels: A decrease in certain antibodies in the blood, which may increase infection risk.

Hepatitis B Virus Reactivation

Ofatumumab has a boxed warning regarding the risk of hepatitis B virus (HBV) reactivation. In individuals who have previously been exposed to HBV, the virus can become active again during or after treatment. This reactivation can lead to severe liver damage, liver failure, and death. Healthcare providers require blood tests to screen for HBV infection before starting treatment. If reactivation occurs, ofatumumab and any concurrent chemotherapy are typically stopped, and antiviral treatment may be initiated.

Progressive Multifocal Leukoencephalopathy (PML)

PML is a rare and potentially fatal brain infection caused by the John Cunningham (JC) virus. It has been reported in patients receiving ofatumumab. Symptoms of PML may include:

• Progressive weakness on one side of the body
• Clumsiness or loss of coordination
• Vision changes or loss of vision
• Confusion or changes in personality and memory

If PML is suspected, the medication is usually suspended immediately while diagnostic tests are performed.

Increased Risk of Infections

Because ofatumumab suppresses the immune system by reducing B-cells, it increases the risk of serious bacterial, fungal, and viral infections. Treatment is generally not started in patients with an active, serious infection. Monitoring for signs of infection, such as fever, chills, or persistent cough, is necessary during and after therapy. Some patients may also experience a decrease in immunoglobulin levels (IgM and IgG), which can further increase infection risk.

Infusion and Injection Reactions

Reactions are common, especially with the first dose. For intravenous administration, reactions may include fever, chills, rash, shortness of breath, and changes in blood pressure. For subcutaneous injections, local site reactions such as redness, pain, itching, or swelling may occur. Most reactions are mild to moderate, but severe or life-threatening reactions can happen.

Vaccinations

Live-attenuated or live vaccines should not be administered during treatment or until B-cell levels have recovered. It is recommended that all required vaccinations be completed at least four weeks before starting ofatumumab for live vaccines, and at least two weeks before for non-live vaccines.

Pregnancy and Fetal Risk

Ofatumumab may cause harm to a developing fetus by depleting fetal B-cells. Females of reproductive potential are advised to use effective contraception during treatment and for at least six months after the final dose. If a patient becomes pregnant while taking this medication, they should inform their healthcare provider immediately.

Pregnancy

There is limited information regarding the safety of ofatumumab during pregnancy. Because ofatumumab targets B-cells in the immune system, it may cause a reduction in B-cells in a developing fetus if used during pregnancy. Animal studies have shown that exposure to similar medications can lead to immune system issues in offspring.

Healthcare providers generally recommend the following:

• Pregnancy Testing: A pregnancy test may be required before starting treatment to ensure you are not pregnant.
• Contraception: Use effective birth control during treatment and for at least 6 months after the final dose.
• Consultation: If you become pregnant or plan to become pregnant, talk to your doctor about the potential risks to the baby and the benefits of the treatment for your condition.

Breastfeeding

It is currently unknown if ofatumumab is excreted in human breast milk. While many large protein medications like ofatumumab are likely to be broken down in an infant's stomach, the potential for side effects in a nursing child has not been fully determined. Decisions regarding breastfeeding while on this medication should be made in consultation with a healthcare provider, weighing the necessity of the drug for the mother against the potential risks to the infant.

Available Forms

Ofatumumab is provided in the following delivery formats:

• Subcutaneous Injection: This form is available as a solution in single-dose prefilled autoinjector pens or single-dose prefilled syringes. It is designed for administration into the fatty tissue under the skin.
• Intravenous Infusion: This form is available as a concentrated solution in single-dose vials. It must be diluted by a healthcare professional before being administered directly into a vein.

FDA Approval and Indications

The U.S. Food and Drug Administration (FDA) has approved ofatumumab for the treatment of specific autoimmune and oncological conditions. It is currently indicated for:

• Relapsing forms of multiple sclerosis (MS) in adults, which includes clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease.
• Chronic lymphocytic leukemia (CLL) in patients who have not received prior treatment or those whose disease is no longer responding to other therapies.

Boxed Warning

Ofatumumab carries a boxed warning, the most serious type of warning required by the FDA. This warning concerns the risk of hepatitis B virus (HBV) reactivation. In some patients, the virus has become active again during or after treatment, which can lead to severe liver problems, liver failure, or death. Healthcare providers are required to perform blood tests to screen for HBV infection before starting treatment and must monitor patients with a history of the virus for signs of reactivation.

Other Regulatory Considerations

The FDA has also issued safety communications regarding the risk of Progressive Multifocal Leukoencephalopathy (PML). PML is a rare but serious brain infection caused by a virus that can occur in patients with weakened immune systems. Patients are monitored for new or worsening neurological symptoms while taking this medication. There are no Risk Evaluation and Mitigation Strategies (REMS) currently required for ofatumumab, but it must be administered according to specific safety guidelines to manage infusion or injection-related reactions.

Factors Affecting Cost

The price of ofatumumab can vary based on several factors:

• Brand Name: Ofatumumab is available as Kesimpta (for multiple sclerosis) and Arzerra (for chronic lymphocytic leukemia). The pricing and billing structures for these brands differ.
• Administration: Kesimpta is a subcutaneous injection that patients often self-administer at home, while Arzerra is an intravenous infusion given by healthcare professionals in a clinic or hospital. Infusion-related costs may include facility fees.
• Insurance Coverage: Most insurance plans, including Medicare and private insurers, cover ofatumumab, though they often require prior authorization. Your specific plan determines your copay, coinsurance, and deductible responsibilities.

Financial Assistance

Because ofatumumab is a specialty biologic medication, manufacturers and other organizations may offer support to help manage costs:

• Patient Assistance Programs: Manufacturers often provide programs for eligible patients who are uninsured or underinsured to receive the medication at a reduced cost or for free.
• Copay Cards: For patients with commercial insurance, copay savings cards may be available to reduce out-of-pocket expenses.

Patients should consult with their healthcare provider, insurance company, or a specialty pharmacy to determine the exact cost of their treatment plan.