The U.S. Food and Drug Administration (FDA) approved the treatment for the prevention of acute NMOSD attacks in adult patients who are positive for aquaporin-4 immunoglobulin G (AQP4-IgG) antibodies. Patients receive the treatment as a subcutaneous (under-the-skin) injection every four weeks.
How does Enspryng work?
NMOSD is a rare autoimmune disease. It primarily results in inflammation and damage to the optic nerve and the spinal cord. Two-thirds or more of patients with NMOSD have elevated levels of the AQP-IgG antibodies in their blood. These antibodies target support cells in the nervous system called astrocytes. When AQP-IgG binds to astrocytes, this triggers a chain reaction in the immune system called the complement pathway. Activation of the complement pathway causes inflammation. This inflammation damages astrocytes as well as the nerve cells around them. That ultimately leads to the neurological symptoms of NMOSD.
Enspryng is a recombinant humanized IgG2 antibody that targets the interleukin-6 (IL-6) receptors. These receptors play an important role in inflammation. By binding to the receptors, Enspryng inhibits IL-6 from binding to them, which blocks IL-6 signaling and reduces the immune response. Enspryng is a version of another treatment that targets IL-6 called tocilizumab. However, researchers modified it to be able to bind to and block more receptors.
Enspryng in clinical trials
Researchers investigated Enspryng in two double-blind, randomized, placebo-controlled, Phase 3 clinical trials.
One trial, SAkuraStar (NCT02073279), investigated Enspryng without other treatments. The second, SAkuraSky (NCT02028884), investigated it as an add-on therapy to patients’ usual immunosuppressant therapy. SAkuraStar recruited patients, ages 18 to 74 while SAkuraSky also included adolescents, making the patient age range 12 to 74.
In the SakuraSky trial, researchers randomized AQP4-IgG positive and negative patients with NMOSD 1:1 and those in the SAkuraStar trial 2:1, to receive either subcutaneous injections of 120 mg of Enspryng or a matching placebo. Patients received injections at weeks 0, 2, and 4. They then received injections every four weeks.
In SAkuraSky, patients continued in the double-blind portion of the trial (receiving either placebo or Enspryng) until they had a relapse or until the total number of relapses in the study reached 26. At this point, patients entered the open-label portion of the trial. This was the case regardless of whether they were initially receiving Enspryn or the placebo. In the open-label portion, all patients received Enspryng at weeks 0, 2, and 4 continuing every four weeks.
Patients in SAkuraStar continued in the double-blind portion until they had a relapse, the total number of relapses for the study reached 44, or 1.5 years had passed after the last patient began receiving injections.
Researchers published the results of the SAkuraSky trial in The New England Journal of Medicine in 2019. They showed that a total of 83 patients enrolled, with 41 receiving Enspryng and 42 receiving placebo. During the double-blind portion of the trial, only eight patients (20%) receiving Enspryng had a relapse compared to 18 (43%) of those receiving placebo. Fifty-five of the patients enrolled were positive for AQP4-IgG antibodies. Only three of 27 (11%) patients on Enspryng had a relapse, while 12 of 28 (43%) receiving the placebo relapsed. In patients who were negative for the antibody, five of 14 (36%) receiving Enspryng relapsed compared to six of 14 (43%) receiving the placebo. The rates of adverse events (side effects) and infection did not differ between the two groups. The SAkuraSky trial continues in the open-label phase. Researchers estimate it will conclude in March 2022.
A total of 95 patients enrolled in the SAkuraStar trial. Researchers published the results of the trial in The Lancet Neurology in 2020. They showed that 19 of 63 (30%) participants who received Enspryng had relapses during the placebo-controlled portion of the trial compared to 16 of the 32 (50%) patients receiving the placebo. The rate of adverse events between the two groups was similar. The SAkuraStar trial also continues in the open-label phase. Researchers estimate it also will conclude in March 2022.
The FDA approved Enspryng for use in adults with AQP4-IgG positive NMOSD in August 2020 based on the results from these two trials.
Additonal analysis of the results, as well as milestones to the approval of the drug, published in Drugs showed that patients taking Enspryng continued to have a lower relapse rate than those taking the placebo. In an analysis of pooled data from both studies, patients who received Enspryng had a 58% reduced risk of relapse compared to the placebo.
Researchers presented pooled data from the double-blind and open-label extension portions of both trials at the MSVirtual2020 conference. Across both studies, during the double-blind section, patients receiving Enspryng had a 79% reduced risk of severe relapses compared to placebo. In a separate analysis, pooled data including both the double-blind and open-label portions of the study showed that the risk of relapse was 51% less compared to the original placebo groups. In patients positive for AQP4-IgG, there was a 66% reduction in risk.
Patients taking Enspryng may be at higher risk of serious infections such as tuberculosis and reactivation of the hepatitis B virus. They also may experience serious allergic reactions, have high liver enzymes, and low neutrophils (a type of immune cell).
The most common side effects are irritation of the nose and throat, headache, infection of the upper respiratory tract, stomach pain, rash, joint pain, pain in the extremities, and nausea.
Last updated: Dec. 2, 2020
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