Therapy Areas: Respiratory
Horizon Therapeutics Receives CHMP Positive Opinion for Uplinza (inebilizumab) as a Monotherapy for the Treatment of Adult Patients with Neuromyelitis Optica Spectrum Disorder (NMOSD)
12 November 2021 - - The Committee for Medicinal Products for Human Use of the European Medicines Agency has adopted a positive opinion recommending marketing authorization for Uplinza (inebilizumab) as a monotherapy for the treatment of adult patients with neuromyelitis optica spectrum disorder (NMOSD) who are anti-aquaporin-4 immunoglobulin G seropositive (AQP4-IgG+), Dublin-based Horizon Therapeutics plc (NASDAQ: HZNP) said.

Uplinza has been granted orphan designation by the European Commission.

That designation is subject to additional review by the Committee for Orphan Medicinal Products.

Uplinza has not been approved for commercial use in the European Union.

Based on the CHMP recommendation, a decision by the EC, if granted, would authorize marketing approval in the EU.

This centralized marketing authorization would be valid in all EU Member States, as well as in Iceland, Liechtenstein and Norway.

Uplinza was approved by the FDA in June 2020 and by the Japanese Ministry of Health, Labour and Welfare in March 2021 as a targeted CD19 B-cell depleting antibody for adult patients with AQP4-IgG+ NMOSD, to reduce the risk of attacks.

Uplinza is the only approved NMOSD therapy in the US that has demonstrated a clinically relevant and durable effect on delaying worsening of disability, with a significant reduction in hospitalization.

In Japan, Mitsubishi Tanabe Pharma Corp. has the rights for development and commercialization of Uplinza.

Long-term Uplinza treatment has been shown to be well tolerated and provide a sustained reduction in NMOSD attack risk for four or more years.

NMOSD is a rare, severe autoimmune disease where the body's defense cells (B-cells) start to attack the optic nerve, spinal cord and brain stem.

NMOSD is often misdiagnosed as multiple sclerosis (MS) and primarily damages the optic nerve(s) and spinal cord, causing permanent blindness, muscle weakness and paralysis.

NMOSD is characterized by unpredictable attacks and severe disability that often occurs following the first attack, accumulating with each subsequent relapse.

Preventing these attacks is the primary goal for disease management.6 UPLIZNA works by depleting B-cells in a targeted manner, and patients need only take it once every six months, via infusion, following an initial two treatments spaced two weeks apart.

AQP4 is a membrane protein that is predominantly found in the central nervous system. It has a protective effect by regulating the water homeostasis, a self-regulating process, to maintain the stability of the physiological function in the body.

A defining feature of NMOSD (seen in approximately 80% of patients) is the presence of serum autoantibodies which work against AQP4, leading to severe attacks in the central nervous system, resulting in substantial and often permanent disability.

Globally, the prevalence of NMOSD is approximately 0.5–4/100,000 people.

Europe has an estimated disease population of at least 7,300 patients, 75-80% of which are AQP4-IgG+. Each year, approximately 370 new patients in Europe are diagnosed with NMOSD.

The CHMP positive opinion was granted based on the data from the N-MOmentum clinical development program (NCT02200770), which found that UPLIZNA monotherapy reduced the risk of relapse by 77% compared to placebo in AQP4-IgG+NMOSD adult patients.

NMOSD is a unifying term for neuromyelitis optica and related syndromes. NMOSD is a rare, severe, relapsing, neuroinflammatory autoimmune disease that attacks the optic nerve, spinal cord, brain and brain stem.

Approximately 80% of all patients with NMOSD test positive for anti-AQP4 antibodies.

AQP4-IgG binds primarily to astrocytes in the central nervous system and triggers an escalating immune response that results in lesion formation and astrocyte death.
Anti-AQP4 autoantibodies are produced by plasmablasts and plasma cells.

These B-cell populations are central to NMOSD disease pathogenesis, and a large proportion of these cells express CD19.

Depletion of these CD19+ B-cells is thought to remove an important contributor to inflammation, lesion formation and astrocyte damage. Clinically, this damage presents as an NMOSD attack, which can involve 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 cumulative damage and disability.17,18 NMOSD occurs more commonly in women and may be more common in individuals of African and Asian descent.

N-MOmentum was a multicenter, double-blind, randomized placebo-controlled Phase 2/3 clinical trial that was conducted in 25 countries. Participants were randomly assigned (3: 1 with a ratio AQP4+: n=213 and AQP4-: n=17) to receive 300 mg of intravenous UPLIZNA or placebo.

The study consisted of a 28-week randomized-controlled period, followed by an optional open-label period of at least two years. The OLP lasted approximately four years, producing long-term data for a subset of patients (n=94 AQP4+ patients).


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