Therapy Areas: Central Nervous System
Horizon Therapeutics Receives European Commission Approval of Uplizna for the Treatment of Adults with Neuromyelitis Optica Spectrum Disorder
3 May 2022 - - The European Commission has approved Uplizna (inebilizumab) as monotherapy for the treatment of adult patients with neuromyelitis optica spectrum disorder (NMOSD) who are anti-aquaporin-4 immunoglobulin G seropositive (AQP4-IgG+), following the positive opinion adopted by the Committee for Medicinal Products for Human Use of the European Medicines Agency on 11th November, 2021, Dublin-based Horizon Therapeutics plc (NASDAQ: HZNP) said.

People impacted by NMOSD live with unpredictable attacks; 90% will experience repeat attacks within five years of an initial attack.

Even a single NMOSD attack can result in significant, irreversible damage, with each subsequent attack building upon the damage caused by the previous.

This damage is caused when CD19+-expressing B-cell lymphocytes (plasmablasts and some plasma cells) secrete AQP4-IgG, triggering an escalating autoimmune reaction.

Depletion of CD19+ B-cells has proven effective at halting inflammation, lesion formation and astrocyte loss.

As a targeted CD19 B-cell depleter, Uplizna offers a unique mode of action developed specifically to induce broad, deep and durable B-cell depletion and prevent attacks. Maintaining B-cell depletion and preventing attacks are key to limiting cumulative disability within NMOSD.

In the N-MOmentum pivotal clinical trial (2014-000253-36), the largest NMOSD trial to date, UPLIZNA demonstrated a significant reduction in the risk of an NMOSD attack with only two infusions per year, following the initial loading doses.

Additionally, 89% of patients in the AQP4-IgG+ group remained relapse-free during the six-month period post-treatment and more than 83% of patients on treatment remained attack free for at least four years.

Globally, the prevalence of NMOSD is approximately 0.5–4/100,000 people, and women are nine times more likely to be impacted than men.

Consequences of this disease extend beyond the clinical impact, including physical, functional and psychological impact on patients' quality of life.

In Europe, it is estimated that at least 7,300 people live with NMOSD, approximately 80% of whom are AQP4-IgG+.

Each year, approximately 370 new patients in Europe are diagnosed with the disease.

The EC approval of Uplizna results in the granting of a centralised marketing authorisation, which is valid in all EU Member States, as well as in Iceland, Liechtenstein and Norway.

Horizon will work with local health authorities to bring Uplizna to patients in a number of countries across Europe.

Germany will be the first country where Horizon initiates commercialisation efforts.

Uplizna was approved by the US Food and Drug Administration 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.

Mitsubishi Tanabe Pharma Corp. has the rights to develop and commercialise Uplizna in Japan, Thailand, South Korea, Indonesia, Vietnam, Malaysia, Philippines, Singapore and Taiwan.

Hansoh Pharmaceutical Group company Ltd., another strategic partner to Horizon, has also recently received manufacturing and marketing approval from National Medical Products Administration of the People's Republic of China for Uplizna.

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.

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, and nerve pain can all be manifestations of the disease.

Each NMOSD attack can lead to further cumulative damage and disability.

NMOSD occurs more commonly in women and may be more common in individuals of African and Asian descent.

Anti-AQP4 autoantibodies are produced by plasmablasts and some 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.

N-MOmentum was a multicentre, double-blind, randomised placebo-controlled Phase 2/3 clinical trial that was conducted in 25 countries.

A total of 230 participants were enrolled:213 were AQP4-IgG seropositive, and 17 were AQP4 IgG seronegative. Participants were randomly assigned at a ratio of 3 (on treatment) to 1 (on placebo).

The study consisted of a 28-week randomised-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=75 AQP4+ patients).

Horizon is focused on the discovery, development and commercialisation of medicines that address critical needs for people impacted by rare, autoimmune and severe inflammatory diseases.
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