Satralizumab, sold under the brand name Enspryng, is a

humanized monoclonal antibody Humanized antibodies are antibodies from non-human species whose protein sequences have been modified to increase their similarity to antibody variants produced naturally in humans. The process of "humanization" is usually applied to monoclonal ant ...

medication that is used for the treatment of

neuromyelitis optica spectrum disorder Neuromyelitis optica spectrum disorders (NMOSD), including neuromyelitis optica (NMO), are autoimmune diseases characterized by acute inflammation of the optic nerve (optic neuritis, ON) and the spinal cord (myelitis). Episodes of ON and myelitis ...

(NMOSD), a rare

autoimmune disease An autoimmune disease is a condition arising from an abnormal immune response to a functioning body part. At least 80 types of autoimmune diseases have been identified, with some evidence suggesting that there may be more than 100 types. Nearly a ...

. The drug is being developed by

Chugai Pharmaceutical is a drug manufacturer operating in Japan. It is a subsidiary controlled by Hoffmann-La Roche, which owns 62% of the company as of 30 June 2014. The company is headquartered in Tokyo. Osamu Nagayama is the current representative director and c ...

, a subsidiary of

Roche F. Hoffmann-La Roche AG, commonly known as Roche, is a Swiss multinational healthcare company that operates worldwide under two divisions: Pharmaceuticals and Diagnostics. Its holding company, Roche Holding AG, has shares listed on the SIX S ...

. The most common side effects include the common cold (nasopharyngitis), headache, upper respiratory tract infection, inflammation of the lining of the stomach, rash, joint pain, extremity pain, fatigue and nausea. Satralizumab regulates inflammation by inhibiting the

interleukin-6 Interleukin 6 (IL-6) is an interleukin that acts as both a pro-inflammatory cytokine and an anti-inflammatory myokine. In humans, it is encoded by the ''IL6'' gene. In addition, osteoblasts secrete IL-6 to stimulate osteoclast formation. Smooth ...

(IL-6) receptor, a key mediator of the immune response. 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 respon ...

(FDA) considers it to be a

first-in-class medication A first-in-class medication is a pharmaceutical that uses a "new and unique mechanism of action" to treat a particular medical condition. While the Food and Drug Administration's Center for Drug Evaluation and Research tracks first-in-class medicat ...

Medical uses

Satralizumab 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 neuromyelitis optica spectrum disorder (NMOSD) in adults with a particular antibody – people who are anti-aquaporin-4 or AQP4 antibody-positive. NMOSD is a rare autoimmune disease of the central nervous system that mainly affects the optic nerves and spinal cord. In people with NMOSD, the body's immune system mistakenly attacks healthy cells and proteins in the body, most often those in the optic nerves and spinal cord. Individuals with NMOSD typically have attacks of optic neuritis, which causes eye pain and vision loss. Approximately 50% of people with NMOSD have permanent visual impairment and paralysis caused by NMOSD attacks. Estimates vary, but NMOSD is thought to impact approximately 4,000 to 8,000 Americans. NMOSD can be associated with antibodies that bind to a protein called aquaporin-4 (AQP4). Binding of the anti-AQP4 antibody appears to activate other components of the immune system, causing inflammation and damage to the central nervous system.

Contraindications

Vaccination with live-attenuated or live vaccines is not recommended during treatment and should be administered at least four weeks before starting satralizumab.

Side effects

The most common side effects observed were the common cold (nasopharyngitis), headache, upper respiratory tract infection, inflammation of the lining of the stomach, rash, joint pain, extremity pain, fatigue and nausea. The FDA label for satralizumab includes a warning for increased risk of infection, including serious and potentially fatal infections – such as potential reactivation of hepatitis B and tuberculosis. Other warnings and precautions for satralizumab include elevated liver enzymes, decreased neutrophil counts and hypersensitivity reactions.

Pharmacology

Mechanism of action

Satralizumab is a humanized IgG2

monoclonal antibody A monoclonal antibody (mAb, more rarely called moAb) is an antibody produced from a cell Lineage made by cloning a unique white blood cell. All subsequent antibodies derived this way trace back to a unique parent cell. Monoclonal antibodies ca ...

that binds to soluble and membrane-bound human interleukin-6 (IL-6) receptors and thereby prevents IL-6-mediated signal transmission through these receptors. IL-6 is a

pleiotropic Pleiotropy (from Greek , 'more', and , 'way') occurs when one gene influences two or more seemingly unrelated phenotypic traits. Such a gene that exhibits multiple phenotypic expression is called a pleiotropic gene. Mutation in a pleiotropic g ...

cytokine that is produced by a large number of cell types and is involved in a variety of inflammatory processes. Patients with NMO and NMOSD have elevated levels of IL-6 in

cerebro-spinal fluid Cerebrospinal fluid (CSF) is a clear, colorless body fluid found within the tissue that surrounds the brain and spinal cord of all vertebrates. CSF is produced by specialised ependymal cells in the choroid plexus of the ventricles of the bra ...

and serum during periods of active disease. Some of the pro-inflammatory processes involved in NMOSD are thought to involve IL-6, including the formation of pathological autoantibodies against aquaporin-4 (AQP4), and the permeability of the blood-brain barrier to mediators of inflammation.

Efficacy

The effectiveness and safety of satralizumab for the treatment of neuromyelitis optica spectrum disorder (NMOSD) were demonstrated in two 96-week clinical studies. A study of satralizumab as

monotherapy Combination therapy or polytherapy is therapy that uses more than one medication or modality. Typically, the term refers to using multiple therapies to treat a ''single'' disease, and often all the therapies are pharmaceutical (although it can also ...

for NMOSD included 95 adult participants, 64 of whom had antibodies against AQP4 (i.e. were anti-AQP4 positive). During this study, treatment with satralizumab reduced the number of NMOSD relapses by 74% in participants who were anti-AQP4 positive compared to treatment with a

placebo A placebo ( ) is a substance or treatment which is designed to have no therapeutic value. Common placebos include inert tablets (like sugar pills), inert injections (like Saline (medicine), saline), sham surgery, and other procedures. In general ...

(inactive treatment). A study of satralizumab as an

adjuvant In pharmacology, an adjuvant is a drug or other substance, or a combination of substances, that is used to increase the efficacy or potency of certain drugs. Specifically, the term can refer to: * Adjuvant therapy in cancer management * Analgesic ...

immunosuppressant Immunosuppressive drugs, also known as immunosuppressive agents, immunosuppressants and antirejection medications, are drugs that inhibit or prevent activity of the immune system. Classification Immunosuppressive drugs can be classified in ...

treatment for NMOSD included 76 adult participants; 52 were anti-AQP4 positive. Immunosuppressant treatment in combination with satralizumab reduced the rate of relapses in participants who were anti-AQP4 positive by four-fifths compared to immunosuppressant treatment alone. The U.S.

(FDA) approved satralizumab based on evidence from two clinical trials (Trial 1/ NCT02073279 and Trial 2/NCT02028884) of 116 participants with NMOSD who were anti-aquaporin-4 (AQP4) antibody positive. The trials were conducted at 62 sites in the United States, Canada, Europe and Asia. Participants received at random either satralizumab or placebo injections according to the schedule. Neither the participants nor the healthcare providers knew which treatment was being given. In the second trial, all participants were also receiving their current immunosuppressive medications for the treatment of NMOSD. The benefit of satralizumab was evaluated by measuring the time to the first attack and comparing it to placebo. There was no evidence of a benefit in participants who were anti-AQP4 antibody negative in either trial.

Society and culture

Legal status

Satralizumab was approved for the treatment of AQP4-IgG-seropositive NMOSD in Canada, Japan, and Switzerland. Satralizumab was approved for medical use in the United States in August 2020. The U.S.

(FDA) granted the application for satralizumab

fast track The fast track is an informal English term meaning "the quickest and most direct route to achievement of a goal, as in competing for professional advancement". By definition, it implies that a less direct, slower route also exists. Fast track or F ...

and

orphan drug An orphan drug is a pharmaceutical agent developed to treat medical conditions which, because they are so rare, would not be profitable to produce without government assistance. The conditions are referred to as orphan diseases. The assignment of ...

designations. The FDA granted the approval of Enspryng to

Genentech Genentech, Inc., is an American biotechnology corporation headquartered in South San Francisco, California. It became an independent subsidiary of Roche in 2009. Genentech Research and Early Development operates as an independent center within R ...

Inc. Satralizumab is the third approved treatment for NMOSD in the United States.

Names

Satralizumab is the international nonproprietary name (INN) and the United States Adopted Name (USAN).

References

External links

* * * {{Portal bar , Medicine Genentech brands Hoffmann-La Roche brands Monoclonal antibodies Orphan drugs