FDA Approves Kesimpta® (Ofatumumab), the First Self-Administered B-cell Therapy for Relapsing Forms of MS
Updated September 3, 2020
Reviewed by MSAA Chief Medical Officer Barry A. Hendin, MD
On August 20, 2020, Novartis announced that the United States Food and Drug Administration (FDA) approved Kesimpta® (ofatumumab) for adults with relapsing forms of multiple sclerosis (RMS), which includes clinically isolated syndrome, relapsing-remitting disease, and active secondary-progressive disease. Kesimpta is a B-cell therapy, which binds to and depletes B-cells shown to be associated with disease activity in MS. Typically this type of therapy is only available via infusion at a hospital or infusion center; however, Kesimpta is the first self-administered B-cell therapy for MS. It is given monthly via subcutaneous injection at one’s home, providing individuals with MS a new and convenient option for treating their MS.
Kesimpta is a monoclonal antibody, which is a laboratory-produced molecule that fulfills the same functions as the body’s naturally produced antibodies. Antibodies are key components of the immune system that recognize, bind to, and combat cells that can cause harm. Kesimpta is a fully human antibody, meaning that it was developed from human cells, whereas other (nonhuman) monoclonal antibodies are developed from animal cells. This newly approved medication targets CD20, a protein found on the surface of B cells, which are immune system cells believed to contribute to the development of MS.
The approval of Kesimpta is based on results from the Phase III ASCLEPIOS I and II studies, in which Kesimpta demonstrated superiority over Aubagio® (oral teriflunomide) in significantly reducing the annualized relapse rate (ARR), three-month confirmed disability progression (CDP), and the number of gadolinium-enhancing (Gd+) T1 and new or enlarging T2 lesions. These trials examined the efficacy and safety of Kesimpta relative to Aubagio in more than 1,800 people with relapsing-remitting MS (RRMS). Trial participants assigned to the Kesimpta arm of the studies received 20 mg of the monoclonal antibody injected subcutaneously once per month. People in the comparison group took a 14-mg tablet of Aubagio orally each day. This dose is the higher of the two approved doses of Aubagio.
Results of the ASCLEPIOS I and II studies found that Kesimpta demonstrated a significant reduction in ARR, the studies’ primary endpoint, by 51% and 59% (respectively) compared with Aubagio. Kesimpta also showed a relative risk reduction in three-month CDP of 34.4% when compared to Aubagio. In addition, Kesimpta significantly reduced the mean number of both Gd+ T1 lesions (98% and 94% relative reduction, respectively) and new or enlarging T2 lesions (82% and 85% relative reduction, respectively) versus Aubagio.
A separate post hoc analysis demonstrated Kesimpta reduced new disease activity in RMS patients. No evidence of disease activity (NEDA-3) is a measure that requires a person to have no evidence of disease activity as assessed in three ways: absence of relapses; absence of disability worsening; and absence of disease activity as shown on magnetic resonance imaging (MRI). During the course of 12 months, 47% of individuals receiving Kesimpta and 24.5% of those taking Aubagio achieved NEDA-3. For months 12 to 24 of the study, 87.8% of Kesimpta achieved NEDA-3, compared to 48.2% of those receiving Aubagio. The differences for both time periods were statistically significant.
According to Novartis, ofatumumab was first approved by the FDA in 2009 for the treatment of chronic lymphocytic leukemia (CLL), given in a high-dose intravenous infusion. Knowing that B-cells are involved with the development of autoimmune diseases, ofatumumab was then studied as a potential treatment for relapsing forms of multiple sclerosis (RMS).
The clinical development of ofatumumab for RMS and its novel administration required 10 years to complete and more than 2,300 participants to take part in rigorous, international clinical trials. The open-label Phase II APLIOS study was conducted to determine the bioequivalence of subcutaneous delivery of Kesimpta via a prefilled syringe and a Sensoready® autoinjector pen in patients with RMS, versus the traditional intravenous administration.
Side Effects and Warnings
The most common side effects of Kesimpta include upper respiratory tract infection (URTI), with symptoms that include sore throat, runny nose, and headache, as well as headache not related to a URTI. Serious but less-common side effects include: infections; hepatitis B virus (HBV) reactivation; progressive multifocal leukoencephalopathy (PML), a rare but serious brain infection caused by a virus; and a weakened immune system. Other serious side effects include injection-related reactions near the injection site (such as redness, swelling, itching, or pain) and other injection reactions such as fever, headache, pain in the muscles, chills, and tiredness.
Individuals with an active hepatitis B virus (HBV) infection should not take Kesimpta. Those considering Kesimpta need to provide the following information to their healthcare professional:
- If they may have any type of infection
- If they have ever taken, currently take, or plan to take medicines that affect the immune system
- If they have had a recent vaccination or are scheduled to receive any vaccinations
- If they are pregnant, think they might be pregnant, or plan to become pregnant (it is not known if Kesimpta will harm an unborn baby)
- If they are breastfeeding or plan to breastfeed (it is not known if Kesimpta passes into breast milk)
- All medicines they take, including prescription and over-the-counter medicines, vitamins, and herbal supplements
Statement from MSAA’s Chief Medical Officer
MSAA’s Chief Medical Officer Dr. Barry A. Hendin explains, “We welcome another highly effective disease-modifying therapy directed against B-cells for the treatment of relapsing forms of MS. The most obvious difference between the newly approved Kesimpta and the previously approved B-cell therapy Ocrevus (ocrelizumab), is the route of delivery. Kesimpta is taken once monthly by subcutaneous injection at home, while Ocrevus is taken twice yearly by IV infusion, typically at an IV center. Treatment selection will largely depend on which type of administration a patient and his or her clinician prefer, in conjunction with the insurance company’s preferences. Regardless of which treatment is selected, we are always pleased to see a new option added to our ever-expanding variety of effective disease-modifying therapies aimed at slowing MS disease activity and preserving function.”
Availability and Patient Support
According to Novartis, Kesimpta® (ofatumumab) 20-mg injection is expected to be available in the United States in September to individuals with relapsing forms of MS. Novartis is offering Alongside Kesimpta®, a program that provides education and resources to individuals who are taking Kesimpta. In addition to financial and reimbursement support, the program also provides supplemental injection training and ongoing support to people who have been prescribed Kesimpta.
Novartis explains that they are committed to helping people afford Kesimpta and is offering a $0 copay for patients with commercial insurance, and will provide free medication while working through benefit verification for eligible commercially-insured people. Individuals can learn more by calling 1-855-KESIMPTA (855-537-4678) or by visiting www.kesimpta.com.
For More Information
For general information or to speak with a trained Client Services Specialist, please call MSAA’s Helpline at (800) 532-7667, extension 154. Questions to MSAA’s Client Services department may also be emailed to MSquestions@mymsaa.org.
Written by Susan Wells Courtney, MSAA Senior Writer
Portions written by Tom Garry, Medical Writer
Reviewed by Dr. Barry A. Hendin, MSAA Chief Medical Officer