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Biomarker Analysis Publication Highlights Key Signals of Disability Worsening Associated With Neuromyelitis Optica Spectrum Disorder (NMOSD) Attacks, Illustrates Efficacy of UPLIZNA® (inebilizumab-cdon)

-- Analysis in The Journal of Neurology, Neurosurgery and Psychiatry demonstrate the direct effect of UPLIZNA on levels of sNFL and sGFAP, two key biomarkers strongly associated with NMOSD attacks and disability --

Horizon Therapeutics plc (Nasdaq: HZNP) today announced the publication of new data from the Phase 3 N-MOmentum pivotal trial of UPLIZNA, which offer insights on serum biomarkers that signal acute attacks and disability worsening associated with NMOSD and illustrate the role of UPLIZNA in reducing these biomarker levels, potentially reducing the frequency and severity of these attacks. The results of this analysis are published in The Journal of Neurology, Neurosurgery and Psychiatry.

NMOSD is most notably associated with acute attacks, which can cause irreversible damage to the optic nerve, spinal cord, brain and brain stem. Disease management goals are focused on prevention of attacks, as well as understanding and tracking biomarkers that could signal these attacks. The N-MOmentum pivotal trial of UPLIZNA, which demonstrated the effects of the treatment in reducing the attacks associated with NMOSD, included analyses of biomarkers linked to disease activity and neuronal injury: serum neurofilament light chain (sNfL, a structural protein increasingly recognized as a signal of neuronal injury), serum glial fibrillary acidic protein (sGFAP, a marker previously found to correlate with NMOSD attacks), ubiquitin C-terminal hydrolase L1 (sUCHL1), and tau (sTau).

The trial identified important biomarker trends associated with NMOSD attacks. Throughout the 28-week randomized controlled trial period (RCP) and the two-year open-label follow-up period, the concentration of all four biomarkers increased during NMOSD attacks, and in the days leading up to attacks. Of the four biomarkers evaluated in the trial, sNfL measured at the time of attack was the strongest predictor of worsening disability during and after attacks (as measured by Expanded Disability Status Scale, or EDSS). The strong link suggests that higher sNfL levels may be associated with more severe attacks and increased risk of residual disability. However, only levels of sGFAP were determined to be predictive of future attacks, building upon prior research studying that biomarker in particular.

“This analysis provides valuable insights into how we can improve care for people with NMOSD by integrating easily accessible serum biomarker assessments into treatment decision-making,” said Orhan Aktas, M.D., Professor at the Department of Neurology, Medical Faculty at Heinrich-Heine-University, Düsseldorf, Germany. “Conducting assessments of the sNfL biomarker during an attack can inform clinicians about the attack severity and the likelihood of residual disability in the patient, and therefore may guide therapeutic interventions to help preserve their long-term outcomes. Combination with other select serum biomarkers such as sGFAP may further increase prediction of clinical activity and, thus, prognosis in this devastating disorder.”

Importantly, biomarker changes among UPLIZNA-treated participants in the trial reinforced the effects of this medicine. Compared with placebo, UPLIZNA was shown to hinder biomarker elevation during attacks while reducing biomarker levels over time in the absence of attacks. Participants treated with UPLIZNA had significantly lower levels of sNfL at the end of the RCP compared to placebo (22% vs. 45% of participants with sNfL levels above 16 mg/mL, respectively), and numerically lower levels of the other three biomarkers. Among patients who did experience attacks, those treated with UPLIZNA had lower biomarker levels during attacks versus those who received placebo, reflecting potentially less severe events, and sGFAP levels were significantly lower with UPLIZNA among those who did not experience attacks versus placebo.

“These findings support the strong clinical profile of UPLIZNA as a leading therapeutic option for NMOSD, with compelling evidence of its direct effects on critical biomarkers that signal disease activity and disability,” said Kristina Patterson, M.D., Ph.D., senior medical director, neuroimmunology medical affairs, Horizon. “The availability of these data in a rare and challenging disease like NMOSD can inform disease management strategies and contribute to improved outcomes for this population over time.”

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.1-2 Approximately 80% of all patients with NMOSD test positive for anti-AQP4 antibodies.3 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.4

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 CD19.5 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.4-6 Loss of vision, paralysis, loss of sensation, bladder and bowel dysfunction, nerve pain and respiratory failure can all be manifestations of the disease.7 Each NMOSD attack can lead to further cumulative damage and disability.8-9 NMOSD occurs more commonly in women and may be more common in individuals of African and Asian descent.10-11



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


UPLIZNA is contraindicated in patients with:

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


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

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 and follow us on Twitter, LinkedIn, Instagram and Facebook.

Forward-Looking Statements

This press release contains forward-looking statements, including statements regarding the potential benefits of UPLIZNA, future use of biomarker analyses and Horizon’s research and development plans. These forward-looking statements are based on management's 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, but are not limited to, risks regarding whether future results of clinical trials will be consistent with preliminary results or results of prior trials or other data or Horizon’s expectations, the risks associated with clinical development and adoption of novel medicines and risks related to competition or other factors that may change physician treatment strategies. For a further description of these and other risks facing Horizon, please see the risk factors described in Horizon’s filings with the United States Securities and Exchange Commission, including those factors discussed under the caption “Risk Factors” in those filings. Forward-looking statements speak only as of the date of this press release and Horizon undertakes no obligation to update or revise these statements, except as may be required by law.


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  2. What is NMO? Accessed April 15, 2021.
  3. What We Know About NMO. Accessed Aug. 2, 2022.
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