Horizon Therapeutics announced new Uplizna (inebilizumab-cdon) data being presented at the American Academy of Neurology’s 73rd Annual Meeting being held virtually April 17-22, 2021 (AAN 2021), including new, end-of-study data from the open-label extension period of the pivotal N-MOmentum trial in patients with NMOSD. Uplizna is the first and only FDA-approved anti-CD19 B-cell depleting humanized monoclonal antibody for the treatment of adult patients with anti-aquaporin-4 (AQP4) antibody positive NMOSD.
“The goal of the open-label extension period was to better understand the long-term administration of Uplizna beyond the 28-week time frame that was originally studied in the randomized controlled period of the trial,” Bruce Cree, MD, PhD, MAS, professor of clinical neurology at the University of California San Francisco Weill Institute for Neurosciences and primary study investigator, said in a company news release. “These data are important because they provide further evidence that Uplizna can safely be used by NMOSD patients for an extended period of time, for at least 4 years, and that the medicine provides a sustained effect on attack risk.”
Outcomes Maintained Throughout the Four-Year Open-Label Period
The N-MOmentum phase 2/3 clinical trial consisted of a 28-week randomized controlled period (RCP), where study participants received Uplizna or placebo. Following the completion of this period, patients could enter into the OLP for at least 2 years, during which all patients (n=216) received Uplizna 300 mg every 6 months, with follow-up visits at weeks 2, 4, 13, 26 and 39 of the OLP and every 26 weeks thereafter.
Key OLP findings include (P15.076)*:
- Long-term Uplizna treatment provided a sustained reduction in NMOSD attack risk from baseline, regardless of when treatment was initiated: 87.7 percent of patients who originally received Uplizna in the RCP (n=165) and 83.4 percent of patients who originally received placebo in the RCP (n=51) remained attack-free during the OLP for at least 4 years.
- The vast majority of attacks occurred in the first year of treatment.
- Uplizna treatment was associated with lesion reduction shown by MRI. The mean number of active lesions was similar during the OLP to the number observed in patients who received Uplizna during the RCP.
Key OLP safety findings include (P15.100)*:
- Treatment with Uplizna was generally well-tolerated for at least 4 years.
- No new safety signals were identified with prolonged Uplizna treatment and Uplizna-mediated B-cell depletion.
- Rates of infection or serious infection did not increase with prolonged Uplizna treatment.
- Levels of immunoglobins declined over time and continued to fall up to 5 years after the start of the OLP. No clear association between low IgG levels and severe infection can be established.
- Infusion-related reactions during the N-MOmentum trial were generally mild, with no unexpected safety concerns identified during continued dosing in the OLP (P15.211).
Data from the OLP were also recently presented at the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) 2021 Forum. Of note, one poster featured data with Uplizna in NMOSD patients who had previous rituximab exposure. Seventeen subjects who enrolled in the N-MOmentum study had previous rituximab treatment. The annual relapse rate for those with prior rituximab exposure was .083 compared to an annual relapse rate of .102 for those without prior rituximab exposure.
“For people living with Uplizna, attacks can cause devastating and often permanent disability, including blindness and paralysis,” said Quinn Dinh, vice president, medical affairs, Horizon. “Having a treatment that can be administered twice a year after the initial doses and that has supportive long-term data, is an important advancement for the NMOSD community.”
A separate study presented at AAN (P2.017)* evaluated patient-reported pain scores for each of five body areas (eyes, arms, legs, upper back and lower back) in the previous 24 hours, every 4 weeks during the RCP of the N-MOmentum trial, as well as during NMOSD attacks. The study used the 11-point Pain Numeric Rating Scale (NRS-11), where 0 equals no pain and 10 equals the worst pain. Across the five body areas, patients in both groups reported episodic, rather than persistent pain during the RCP. Also in the RCP, fewer patients who received Uplizna (56 percent) than placebo (77 percent) reported a ≥3-point worsening in NRS-11 score relative to baseline.
*Note: These abstracts only provide interim results, full posters provide end-of-study results.
Patient Attitudes Towards NMOSD Diagnosis and Treatment
To improve understanding of NMOSD patients’ experience throughout the course of their disease, a comprehensive survey was administered to 151 people living with NMOSD. The survey results demonstrate the importance of finding the right specialist who can identify appropriate screening tests that will lead to an earlier diagnosis and progression toward better patient outcomes.
Key findings include (P2.106):
- The average time to NMOSD diagnosis was 2.2 years, and over 10 years for some.
- Only 11 percent of survey participants were diagnosed with NMOSD when symptoms first appeared.
- 34 percent first shared their symptoms with an emergency room doctor and 34 percent first shared their symptoms with a primary care physician.
- Fear (57 percent) and frustration (40 percent) were the most-commonly reported emotions experienced during initial visits with a medical provider.