Viela Bio Announces U.S. FDA Approval of UPLIZNA™ (inebilizumab-cdon) for the Treatment of Neuromyelitis Optica Spectrum Disorder (NMOSD)
“NMOSD is an extremely challenging disease to treat. Patients experience unpredictable attacks that can lead to permanent disability from blindness and paralysis. In addition, each subsequent attack may result in a cumulative worsening of disability. In the pivotal N-MOmentum trial, UPLIZNATM—a humanized CD19-directed monoclonal antibody—significantly reduced the risk of attacks and also reduced hospitalizations when given as a monotherapy,” said
NMOSD is a rare, severe, neuroinflammatory autoimmune disease that attacks the optic nerve, spinal cord and brain stem. In addition to potentially irreversible blindness and paralysis, patients may also experience loss of sensation, bladder and bowel dysfunction, nerve pain and respiratory failure. It is estimated that there are approximately 10,000 people in the
“As an organization that understands and represents the struggle of patients and their loved ones affected by NMOSD, we are pleased that now there is another treatment option that could reduce their attacks, which can lead to devastating and irreversible disability,” said
The approval of UPLIZNATM—which previously received Breakthrough Therapy and Orphan Drug designations from the FDA—is based in part on results from the pivotal N-MOmentum trial, the largest study ever conducted in a real-world spectrum of adults with NMOSD. The global, placebo-controlled study—which enrolled 213 anti-AQP4 antibody positive patients and 17 anti-AQP4 antibody negative patients—met its primary endpoint by demonstrating a statistically significant reduction in risk of NMOSD attacks. Specifically, 89% of patients in the anti-AQP4 antibody positive group remained relapse-free during the six-month period post-treatment, compared to 58% of the patients taking placebo. UPLIZNATM also demonstrated statistically significant benefits in key secondary endpoints, including reductions in NMOSD-related hospitalizations. Additionally, UPLIZNATM demonstrated a favorable safety and tolerability profile. Across both the randomized and open-label treatment in Study 1, the most common adverse reactions (greater than 10%) were urinary tract infection (20%), nasopharyngitis (13%), infusion reaction (12%), arthralgia (11%), and headache (10%). The results from the N-MOmentum trial were published in the peer-reviewed journal, The
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Study Design Overview and Efficacy Results Summary
Patients in the N-MOmentum trial were randomized 3:1 (UPLIZNATM to placebo) to receive two introductory doses of 300 mg of UPLIZNATM monotherapy or placebo at Day 1 and Day 15. The patients were followed for a total of 197 days. Following that randomized-controlled period (RCP), patients were given the option to enter an open-label extension period, in which every participant received 300 mg of UPLIZNATM monotherapy every 6 months. The study was concluded early on the recommendation of the independent data monitoring committee, based on evidence of efficacy. Results from the anti-AQP4 antibody positive patient subgroup are shown in the chart below.
| UPLIZNATM N = 161 |
Placebo N = 52 |
|
| Time to Adjudication Committee-Determined Relapse (Primary Efficacy Endpoint) | ||
| Number (%) of patients with relapse | 18 (11.2%) | 22 (42.3%) |
| Hazard ratio (95% CI)a | 0.227 (0.121, 0.423) | |
| p-valuea | < 0.0001 | |
a Cox regression method, with placebo as the reference group.
1Jarius S, Wildemann B. Aquaporin-4 antibodies (NMO-IgG) as a serological marker of neuromyelitis optica: a critical review of the literature. Brain Pathol. 2013;23(6):661-683.
2 Flanagan EP. Ann Neurol. 2016;79(5):775-783.
About Neuromyelitis Optica Spectrum Disorders (NMOSD)
NMOSD is a unifying term for neuromyelitis optica (NMO) and related syndromes. NMOSD is a rare, severe, relapsing, neuroinflammatory autoimmune disease that can be fatal. Approximately 80% of all patients with NMOSD test positive for anti-AQP4 antibodies.
These AQP4 autoantibodies are produced by CD19+ B cells and bind primarily to astrocytes in the central nervous system. Binding of AQP4 antibodies to central and peripheral nervous system cells is believed to trigger attacks, which can damage the optic nerve, spinal cord and brain. Loss of vision, paralysis, loss of sensation, bladder and bowel dysfunction, nerve pain and respiratory failure can all be manifestations of the disease. Each NMOSD attack can lead to further damage and disability. NMOSD occurs more commonly in women and may be more common in individuals of African and Asian descent.
About N-MOmentum
N-MOmentum, the largest clinical study ever conducted in NMOSD, was a double-blind, placebo-controlled clinical trial of 213 patients who are anti-AQP4 antibody positive and 17 who are anti-AQP4 antibody negative (n=230). In the trial, patients were randomized to receive two intravenous doses of UPLIZNATM (inebilizumab-cdon) monotherapy or placebo and followed for 6.5 months. Patients were subsequently given the option to enter into an open-label extension in which all patients receive inebilizumab every 6 months. The primary endpoint was time from treatment initiation to occurrence of an NMOSD attack, which was reviewed by an independent, blinded external Adjudication Committee. NMOSD attack diagnosis was standardized using 18 clinically meaningful criteria that were developed for the study. The open-label extension portion of the study is ongoing. More information can be found on clinicaltrials.gov (Study NCT02200770).
Additional Clinical Investigation
A Phase 2 trial with inebilizumab is ongoing in kidney transplant desensitization, with an additional Phase 3 trial planned in myasthenia gravis and a Phase 2b trial planned in IgG4-related disease. For more information on ongoing clinical trials, please visit www.clinicaltrials.gov and enter the search term “Viela.”
IMPORTANT SAFETY INFORMATION
UPLIZNATM is contraindicated in patients with:
- A history of life-threatening infusion reaction to UPLIZNATM
- Active hepatitis B infection
- Active or untreated latent tuberculosis
WARNINGS AND PRECAUTIONS
Infusion Reactions: UPLIZNATM can cause infusion reactions, which can include headache, nausea, somnolence, dyspnea, fever, myalgia, rash, or other symptoms. Infusion reactions were most common with the first infusion but were also observed during subsequent infusions. Administer pre-medication with a corticosteroid, an antihistamine, and an anti-pyretic.
Infections: The most common infections reported by UPLIZNATM-treated patients in the randomized and open-label periods included urinary tract infection (20%), nasopharyngitis (13%), upper respiratory tract infection (8%), and influenza (7%). Delay UPLIZNATM administration in patients with an active infection until the infection is resolved.
Increased immunosuppressive effects are possible if combining UPLIZNATM with another immunosuppressive therapy.
The risk of hepatitis B virus (HBV) reactivation has been observed with other B-cell-depleting antibodies. Perform HBV screening in all patients before initiation of treatment with UPLIZNATM. Do not administer to patients with active hepatitis.
Although no confirmed cases of Progressive Multifocal Leukoencephalopathy (PML) were identified in UPLIZNATM clinical trials, JC virus infection resulting in PML has been observed in patients treated with other B-cell-depleting antibodies and other therapies that affect immune competence. At the first sign or symptom suggestive of PML, withhold UPLIZNATM and perform an appropriate diagnostic evaluation.
Patients should be evaluated for tuberculosis risk factors and tested for latent infection prior to initiating UPLIZNATM.
Vaccination with live-attenuated or live vaccines is not recommended during treatment and after discontinuation, until B-cell repletion.
Reduction in Immunoglobulins: There may be a progressive and prolonged hypogammaglobulinemia or decline in the levels of total and individual immunoglobulins such as immunoglobulins G and M (IgG and IgM) with continued UPLIZNATM treatment. Monitor the level of immunoglobulins at the beginning, during, and after discontinuation of treatment with UPLIZNATM until B-cell repletion especially in patients with opportunistic or recurrent infections.
Fetal Risk: May cause fetal harm based on animal data. Advise females of reproductive potential of the potential risk to a fetus and to use an effective method of contraception during treatment and for 6 months after stopping UPLIZNATM.
Adverse Reactions: The most common adverse reactions (at least 10% of patients treated with UPLIZNATM and greater than placebo) were urinary tract infection and arthralgia.
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Forward-Looking Statements
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements, other than statements of historical facts, contained in this press release, including statements regarding our strategy, future operations, prospects, plans, objectives of management, our belief that UPLIZNATM provides prescribing physicians an important new treatment option for patients living with NMOSD; our belief that UPLIZNATM could reduce attacks which can lead to devastating and irreversible disability in patients living with NMOSD; our estimate of the number of people in the
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