-- First and only anti-CD19 B-cell-depleting monotherapy for the treatment of adult patients with NMOSD who are anti-aquaporin-4 immunoglobulin G seropositive (AQP4-IgG+) --

-- NMOSD is a devastating rare autoimmune disease that can cause vision loss and paralysis --

Horizon Therapeutics plc (Nasdaq: HZNP) today announced the Brazilian Health Regulatory Agency (ANVISA) has approved UPLIZNA as a monotherapy for the treatment of adult patients with NMOSD who are AQP4-IgG+. This rare autoimmune disease is caused by inflammation in the central nervous system, resulting in severe and recurrent attacks that can lead to permanent disability, such as paralysis and vision loss.¹ An estimated 10,000 people in Brazil live with the disease.²

“This approval is an important part of Horizon’s commitment to helping people worldwide who are living with challenging rare diseases,” said Vikram Karnani, executive vice president, international and global medical affairs, Horizon. “The NMOSD community in Brazil now has an approved medicine that has been proven in clinical studies to provide sustained protection against NMOSD attacks.”

Unlike other autoimmune diseases, patients with NMOSD typically do not fully recover from attacks.³ It is estimated that 69% of patients have severe vision loss in at least one eye within three years of disease onset and 34% may develop permanent motor impairment.^4,5,6 A primary goal of treatment is to help prevent cumulative damage and permanent disability that can be caused by subsequent attacks.

In the N-MOmentum pivotal clinical trial, 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 attack free during the six-month period post-treatment and more than 83% of patients on treatment remained attack free for at least four years.⁷

“NMOSD is an extremely debilitating and life-changing disease that can impact patients physically, socially and economically,” said Douglas Sato, M.D. Ph.D., neurologist, full professor of medicine, Pontifical Catholic University of Rio Grande do Sul (PUCRS). “UPLIZNA is unique in that it prevents attacks by depleting a broad range of B cells, including plasmablasts and plasma cells, and has a very good safety profile in NMOSD patients. This approval represents a significant advancement in the treatment of NMOSD and can provide hope for those who have been struggling with this disease.”

UPLIZNA was approved by the U.S. Food and Drug Administration (FDA) in June 2020, by the Japanese Ministry of Health, Labor and Welfare in March 2021 and by the European Commission (EC) in April 2022.

About Neuromyelitis Optica Spectrum Disorder (NMOSD)

NMOSD is a unifying term for neuromyelitis optica (NMO) and related syndromes. NMOSD is a rare, severe, relapsing, neuroinflammatory autoimmune disease that attacks the optic nerve, spinal cord, brain and brain stem.^1,8 Approximately 80% of all patients with NMOSD test positive for anti-AQP4 antibodies.⁹ 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.¹⁰

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 CD19.¹¹ 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.^10-12 Loss of vision, paralysis, loss of sensation, bladder and bowel dysfunction, nerve pain and respiratory failure can all be manifestations of the disease.¹³ Each NMOSD attack can lead to further cumulative damage and disability.^14,15 NMOSD occurs more commonly in women and may be more common in individuals of African and Asian descent.^16,17

About UPLIZNA (inebilizumab-cdon)

INDICATION

UPLIZNA is indicated for the treatment of neuromyelitis optica spectrum disorder (NMOSD) in adult patients who are anti-aquaporin-4 (AQP4) antibody positive.

IMPORTANT SAFETY INFORMATION

UPLIZNA is contraindicated in patients with:

• A history of life-threatening infusion reaction to UPLIZNA
• Active hepatitis B infection
• Active or untreated latent tuberculosis

WARNINGS AND PRECAUTIONS

Infusion Reactions: UPLIZNA 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 UPLIZNA-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 UPLIZNA administration in patients with an active infection until the infection is resolved.

Increased immunosuppressive effects are possible if combining UPLIZNA 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 UPLIZNA. Do not administer to patients with active hepatitis.

Although no confirmed cases of Progressive Multifocal Leukoencephalopathy (PML) were identified in UPLIZNA 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 UPLIZNA and perform an appropriate diagnostic evaluation.

Patients should be evaluated for tuberculosis risk factors and tested for latent infection prior to initiating UPLIZNA.

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 UPLIZNA treatment. Monitor the level of immunoglobulins at the beginning, during, and after discontinuation of treatment with UPLIZNA 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 UPLIZNA.

Adverse Reactions: The most common adverse reactions (at least 10% of patients treated with UPLIZNA and greater than placebo) were urinary tract infection and arthralgia.

For additional information on UPLIZNA, please see the Full Prescribing Information at www.UPLIZNA.com.

About Horizon

Horizon is a global biotechnology company focused on the discovery, development and commercialization of medicines that address critical needs for people impacted by rare, autoimmune and severe inflammatory diseases. Our pipeline is purposeful: We apply scientific expertise and courage to bring clinically meaningful therapies to patients. We believe science and compassion must work together to transform lives. For more information on how we go to incredible lengths to impact lives, visit www.horizontherapeutics.com and follow us on Twitter, LinkedIn, Instagram and Facebook.

Forward-Looking Statements

This press release contains forward-looking statements, including, but not limited to, statements related to the potential benefits of UPLIZNA. These forward-looking statements are based on management expectations and assumptions as of the date of this press release, and actual results may differ materially from those in these forward-looking statements as a result of various factors. These factors include the actual timing of launching UPLIZNA in Brazil and other markets, whether UPLIZNA is successfully commercialized, and those risks detailed from time-to-time under the caption "Risk Factors" and elsewhere in Horizon’s filings and reports with the SEC. Horizon undertakes no duty or obligation to update any forward-looking statements contained in this press release as a result of new information.

References

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3. Borisow N, Mori M, Kuwabara S, Scheel M and Paul F. Diagnosis and Treatment of NMO Spectrum Disorder and MOG-Encephalomyelitis. Front Neurol. 2018. 9 888 doi 10 3389/fneur.2018.00888.
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