Neuromyelitis Spectrum Disorder (NMOSD)'s first B cell depleting agent!

March 28, 2021/bioon.
com" target="_blank">/--Mitsubishi Tanabe Pharmaceutical Company (MTPC) recently announced that the Japanese Ministry of Health, Labour and Welfare (MHLW) has approved the anti-CD19 bioon.
com/monoclonalDrugs/" target="_blank">monoclonal antibody drug Uplizna (MEDI-551, generic name: inebilizumab) for the treatment of neuromyelitis optica spectrum disorder (NMOSD) , Optic neuromyelitis) patients to prevent disease recurrence.
Uplizna is a new mechanism drug for the treatment of NMOSD.
The convenience of a dosing interval every six months (6 months) will provide a new treatment option for NMOSD patients in preventing the recurrence period.

NMOSD is a central nervous system bioon.
com/tags/%E8%87%AA%E8%BA%AB%E5%85%8D%E7%96%AB/">autoimmune disease characterized by severe optic neuritis and transverse myelitis is characterized, it is a chronic disease.
Recurrence may occur repeatedly, and a single recurrence may cause vision loss or wheelchair mobility.

Uplizna is a humanized anti-CD19 monoclonal antibody, licensed by MTPC from Viela Bio, and has the right to develop and commercialize Uplizna therapy in Japan, Thailand, Korea, Indonesia, Vietnam, Malaysia, the Philippines, Singapore, and Taiwan.
NMOSD and other potential future indications.
On March 15, 2021, Horizon Therapeutics will acquire Viela Bio.

In June 2020, Uplizna received the world's first regulatory approval in the United States: as a maintenance regimen twice a year after the initial dose, it is used to treat anti-aquaporin-4 (AQP4) antibody-positive NMOSD adult patients.
It is estimated that about 80% of NMOSD patients test positive for anti-AQP4 antibodies.
Previously, the bioon.
com/fda/" target="_blank">FDA has granted Orphan Drug Designation (ODD) and Breakthrough Drug Designation (BTD) for inebilizumab to treat NMOSD.

NMOSD (Image source: empr.
com)

It is worth mentioning that Uplizna is the first and only B cell depleting agent approved for the treatment of AQP4 antibody-positive adult patients with NMOSD.
The active pharmaceutical ingredient of Uplizna is inebilizumab, which is a humanized CD19-directed monoclonal antibody with high affinity to CD19.
CD19 is a protein widely expressed in B cells, including plasmablasts and plasmablasts that secrete antibodies.
Some plasma cells.
After inebilizumab binds to CD19, these cells are quickly exhausted from the circulatory system to prevent NMOSD from recurring.

The end of May 2019, Stockhausen medicine (Hansoh Pharma) and Viela Bio reached a strategic cooperation to develop inebilizumab NMOSD and other potential treatment of inflammatory / in China bioon.
com/tags/%E8%87%AA%E8%BA%AB%E5%85%8D%E7%96%AB/">autoimmune and hematological malignant bioon.
com/course_video/chang-fei-bian-ma-RNA-yu-zhong-liu959063.
html">tumor indications.
According to the terms of the agreement, Viela Bio is eligible to receive an upfront cooperation fee and milestone payments of more than $220 million, as well as tiered royalties based on net product sales.
Hausen Pharmaceuticals will be responsible for leading the development and commercialization of inebilizumab in China.

The mechanism of action of Uplizna's active pharmaceutical ingredient inebilizumab (MEDI-551)

This approval is based on data from the key global clinical study N-MOmentum conducted by Viela Bio, which is a large-scale study conducted in adult patients (including Japanese patients) of the real-world lineage of NMOSD.
The study is a global, randomized, double-dummy, placebo-controlled study, enrolling a total of 213 anti-AQP4 antibody-positive patients and 17 anti-AQP4 antibody-negative patients.
In the study, these patients were randomly divided into 2 groups at a ratio of 3:1, and received 2 introductory doses of 300 mg inebilizumab monotherapy or placebo on day 1 and day 15, and were followed up for 6.
5 months (197 day).
After the randomized control period (RCP), patients can choose to enter the open-label expansion period, and all patients receive 300 mg inebilizumab monotherapy every 6 months.
The primary endpoint is the time from the start of treatment to the onset of NMOSD.

According to the recommendations of the Independent Data Monitoring Committee (IDMC) and based on evidence of efficacy, the study ended early.
The data showed that the primary endpoint was reached: after 28 weeks of treatment, in AQP4-IgG seropositive patients, compared with placebo, inebilizumab significantly reduced the risk of an NMOSD attack by 77% (HR=0.
227, p<0.
0001).
In the total treated patient group (including AQP4-IgG seronegative patients), compared with placebo, inebilizumab reduced the risk of an NMOSD attack by 73% (HR=0.
272, p<0.
0001).
At the end of the randomized control period, 89% of AQP4-IgG seropositive patients treated with inebilizumab had no seizures, compared with 58% in the placebo group.

The study also reached key secondary endpoints: Compared with placebo, inebilizumab significantly reduced disability deterioration (15.
5% vs 33.
9%, p=0.
0049), NMOSD-related hospitalization (10/174 patients vs 8/56 patients, p= 0.
01), the frequency of new central nervous system MRI injuries (79/174 patients vs 32/56 patients, p=0.
0034).
In the study, inebilizumab has good safety and acceptable tolerability, and the incidence of adverse events is similar to that of placebo.
The incidence of serious and/or grade ≥3 serious adverse events was similar, 10.
3% in the inebilizumab group and 14.
3% in the placebo group.

png" target="_blank">

NMOSD is a rare, destructive, complement-mediated central nervous system bioon.
com/tags/%E8%87%AA%E8%BA%AB%E5%85%8D%E7%96%AB/">autoimmune disease, characterized by recurrent, recurrence time will result in the gradual accumulation of disability, including blindness and paralysis, and sometimes even premature death.
In NMOSD patients, about 80% of patients have aquaporin-4 (AQP4) autoantibodies.
These AQP4-IgG autoantibodies are thought to be produced by plasmablasts and plasma cells, and are mainly related to the stars in the central nervous system.
Shaped glial cells combine.
The binding of AQP4-IgG antibody to the central nervous system is thought to trigger an attack that damages the optic nerve, spinal cord, and brain.
Blindness, paralysis, loss of sensation, bladder and bowel dysfunction, neuralgia, and respiratory failure may all be manifestations of the disease.
Each NMOSD attack will cause further injury and disability.
NMOSD is more common in women and may be more common in non-whites.

In terms of NMOSD treatment, Alexion's first C5 complement inhibitor Soliris (eculizumab) was approved in 2019, becoming the first drug approved for the treatment of NMOSD.
In December 2020, bioon.
com/tags/%E9%98%BF%E6%96%AF%E5%88%A9%E5%BA%B7/">AstraZeneca announced that it would acquire Alexion for US$39 billion.

In 2020, Roche IL-6R monoclonal antibody Enspryng (satralizumab) was approved for marketing, becoming the second drug approved for the treatment of NMOSD.
It is worth mentioning that Enspryng is the first and only treatment that targets the inhibition of interleukin-6 receptor (IL-6R) activity to treat NMOSD.
The drug is a humanized monoclonal antibody that targets IL-6 receptors to inhibit IL-6 signaling.
IL-6 is a cytokine that is believed to play a key role in the inflammation of NMOSD, triggering the inflammatory cascade, leading to injury and disability.
()

Original source: Manufacturing and Marketing app roval of UPLIZNA for IV Infusion 100mg for the Treatment of Neuromyelitis Optica Spectrum Disorder in Japan-FirstWord Pharma