Siponimod, sold under the brand name Mayzent, is a selective sphingosine-1-phosphate

receptor Receptor may refer to: * Sensory receptor, in physiology, any neurite structure that, on receiving environmental stimuli, produces an informative nerve impulse *Receptor (biochemistry), in biochemistry, a protein molecule that receives and respond ...

modulator for oral use that is used for

multiple sclerosis Multiple sclerosis (MS) is an autoimmune disease resulting in damage to myelinthe insulating covers of nerve cellsin the brain and spinal cord. As a demyelinating disease, MS disrupts the nervous system's ability to Action potential, transmit ...

(MS). It is intended for once-daily oral administration. In March 2019, it was approved in the United States to treat adults with relapsing forms of multiple sclerosis, to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease.

Medical uses

Siponimod is

indicated In medicine, an indication is a valid reason to use a certain test, medication, procedure, or surgery. There can be multiple indications to use a procedure or medication. An indication can commonly be confused with the term diagnosis. A diagnosis ...

for the treatment of secondary progressive multiple sclerosis, which is the progressive neurological decline of multiple sclerosis that happens independent of acute relapses. In active secondary progressive multiple sclerosis, siponimod decreases the risk of disability and multiple sclerosis relapses.

Adverse effects

In clinical trials of siponimod, the most common adverse effects were

headache A headache, also known as cephalalgia, is the symptom of pain in the face, head, or neck. It can occur as a migraine, tension-type headache, or cluster headache. There is an increased risk of Depression (mood), depression in those with severe ...

high blood pressure Hypertension, also known as high blood pressure, is a long-term medical condition in which the blood pressure in the arteries is persistently elevated. High blood pressure usually does not cause symptoms itself. It is, however, a major ri ...

, and liver function test abnormalities.

Pharmacology

Mechanism of action

Siponimod binds selectively to some of the sphingosine-1-phosphate receptor forms—including sphingosine-1-phosphate receptor 1—found on

lymphocyte A lymphocyte is a type of white blood cell (leukocyte) in the immune system of most vertebrates. Lymphocytes include T cells (for cell-mediated and cytotoxic adaptive immunity), B cells (for humoral, antibody-driven adaptive immunity), an ...

s and other cell types. Siponimod may be very similar to fingolimod but preventing

lymphopenia Lymphocytopenia is the condition of having an abnormally low level of lymphocytes in the blood. Lymphocytes are a white blood cell with important functions in the immune system. It is also called lymphopenia. The opposite is lymphocytosis, which r ...

, one of its main side effects, by preventing egress of lymphocytes from lymph nodes. Siponimod may be more selective in the particular sphingosine-1-phosphate receptors (five in number) that it modulates. It is selective for the -1 and -5 SIP receptors.

History

In March 2019, siponimod was approved in the United States to treat adults with relapsing forms of multiple sclerosis, to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease. The efficacy of siponimod was shown in a clinical trial of 1,651 patients that compared siponimod to placebo in people with secondary progressive multiple sclerosis who had evidence of disability progression in the prior two years and no relapses in the three months prior to enrollment. The primary endpoint of the study was the time to three-month confirmed progression in disability. The trial was conducted at 294 centers in Asia, Australia, Canada, Europe, South America, and the United States. The U.S.

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respo ...

(FDA) granted approval of Mayzent to Novartis. Siponimod was approved for medical use in Australia in October 2019. In January 2020, siponimod was approved in the European Union for the treatment of adults with secondary progressive multiple sclerosis with active disease evidenced by relapses or imaging features of inflammatory activity.

References

{{Authority control Azetidines Lipids Multiple sclerosis Drugs developed by Novartis Trifluoromethyl compounds S1P receptor modulators Cyclohexyl compounds Ketoxime ethers