'Uplizna' to bring a shift to the NMOSD treatment strategy

Launch symposium has been held…it is expected to launch within the first half of this year after the reimbursement listing

Benefit of convenience with twice-yearly administration…proven to reduce relapse and have long-term effects

Tanabe Pharma Korea recently held the UPSTREAM Symposium at Voco Seoul Gangnam to celebrate the launch of NMOSD treatment Uplizna in South Korea.

New treatment strategies are emerging for neuromyelitis optica spectrum disorder (NMOSD), a condition where a single relapse can lead to lifelong disability. This shift has been brought about by the introduction of 'Uplizna', a new drug targeting CD19 B cells, for NMOSD treatment in South Korea. Uplizna has been shown to significantly reduce the risk of relapse in AQP4 antibody-positive patients, and medical professionals anticipate that this treatment option will provide patients with a better choice in terms of mechanism and efficacy.

Tanabe Pharma Korea recently held the UPSTREAM Symposium at Voco Seoul Gangnam to celebrate the launch of Uplizna (inebilizumab)in South Korea.

Professor Ho Jin Kim of the Department of Neurology at the National Cancer Center served as the chairperson. Professor Ki Hoon Kim of the Department of Neurology at Severance Hospital and Professor Jeeyoung Oh of the Department of Neurology at Konkuk University Medical Center delivered lectures titled ▲Optimizing the treatment with inebilizumab after rituximab and ▲inebilizumab in practice: identifying appropriate patients, respectively.

Uplizna is a targeted therapy for adult patients with AQP4 antibody-positive NMOSD. It works by targeting and depleting CD19+ B-cells, thereby reducing attacks (relapses) caused by the immune system targeting the optic nerve and spinal cord.

The treatment received U.S. FDA approval in 2020 and was authorized in South Korea in 2021. Tanabe Pharma Korea is currently proceeding with the reimbursement listing process for the drug.

During the symposium, Professor Ki Hoon Kim began by highlighting B-cells and the AQP4-IgG production pathway as core elements of NMOSD pathophysiology.

The professor explained, "Plasma cells are directly linked to the clinical deterioration of NMOSD. Unlike rituximab, which targets only CD20, Uplizna depletes cells up to the pre-CD19 stage, allowing for an approach closer to the underlying cause of the disease."

NMOSD is a rare autoimmune disease characterized by unpredictable, repeated relapses of optic neuritis and myelitis, leading to severe disabilities such as eye pain, blindness, and paraplegia. Approximately seven out of ten NMOSD patients are AQP4 antibody-positive; the formation of these antibodies activates the complement system, which can cause necrosis in the optic nerve and spinal cord.

Notably, 80–90% of patients experience recurrent relapses, thus even a single event can result in fatal outcomes. These symptoms are often irreversible and difficult to recover from, necessitating rapid acute-phase treatment fully.

Previously, NMOSD relapse relied on high-dose steroids or immunosuppressants to suppress symptoms or used rituximab or 'tocilizumab (product name: Actemra)' to prevent relapses. However, as the relapse suppression effects of these treatments were limited, there was a high demand for new options.

Rituximab' clinical limitations have been pointed out. These include non-unified administration protocols, varying B-cell depletion and relapse risks based on FCGR3A genotypes, and high rates of infusion-related reactions (IRR) during the first administration. 

In contrast, evidence was presented that Uplizna is easy to manage with twice-yearly dosing, reduces the risk of relapse by more than 70% in clinical trials, and cuts the rate of worsening on the Expanded Disability Status Scale (EDSS) by more than half. 

Professor Kim summarized, "Uplizna is an option that can supplement the structural limitations for patients who do not respond to rituximab."

In the second session, Professor Oh focused on the timing of switching therapies, which is a challenge in NMOSD treatment.

Professor Oh emphasized, "Defining treatment failure based solely on clear relapses may cause us to miss patients." She presented various clinical patterns, including partial responses, incomplete recovery after severe relapses, and switching due to side effects or infections.

Professor Oh also pointed out that due to strict domestic reimbursement criteria, some patients with "disability creep," where disability accumulates slowly without clear relapses, may miss the window for adjusting their treatment strategy.

Based on actual patient cases, Professor Oh identified characteristics of patient groups requiring a switch from rituximab to Uplizna.

The characteristics include ▲rapid repopulation of CD19+ B-cells, ▲incomplete response due to genotype influence, and ▲difficulty maintaining treatment due to infection burdens such as pneumonia.

Professor Oh also highlighted data showing the sustained efficacy of Uplizna.

The N-MOmentum study, which served as the basis for approval, was a 28-week randomized, placebo-controlled trial that faithfully reflected the NMOSD patient population in real-world clinical settings by including diverse racial and ethnic groups.

In the trial, 89% of the Uplizna group remained relapse-free for 28 weeks, compared to only 58% of the placebo group.

Long-term data also showed sustained efficacy, with an annualized relapse rate (ARR) of 0.03 for patients treated with Uplizna for at least 2.5 years, significantly lower than the approximately 1.0 ARR in the placebo group.

However, because the open-label period (OLP) was non-blinded and uncontrolled, the results might appear more positive due to patient dropout among those with poor prognoses.

Professor Oh assessed that "Uplizna is an option that is not merely as a substitute, but the one that ensures both efficacy and safety when a mechanistic switch is required."

Professor Kim concluded, "Because NMOSD is a disease where a single minor relapse can lead to lifelong disability, establishing an initial strategy and determining the appropriate timing for a switch is paramount," adding, "This symposium was meaningful for refining our understanding of mechanism-based treatment and discussing customized decisions for each patient. The introduction of Uplizna will serve as an opportunity to advance NMOSD treatment strategies to the next level."