Bruce Cree, MD, PhD, MAS, FAAN, offered his perspective on data from the phase 2/3 N-MOmentum trial of the recently approved inebilizumab (Uplizna; Horizon Therapeutics) and why the therapy stands out from other NMOSD treatments.
Bruce Cree, MD, PHD, MAS, FAAN
EARLIER IN 2022, data from the phase 2/3 N-MOmentum trial (NCT02200770) in neuromyelitis optica spectrum disorder (NMOSD) suggested that the FDA-approved treatment being evaluated—inebilizumab (Uplizna; Horizon Therapeutics)—is effective, not only for patients who have had more long-term disease, but for those with only a single relapse prior to treatment.1,2
The data show that of the 37 individuals with only 1 attack prior to study enrollment, only 4.2% (n = 1) experienced relapse in the group treated with inebilizumab (n = 24) compared with 23.1% (n = 3) of the placebo cohort (n = 13) (HR, 0.160; 95% CI, 0.017-1.542). Additionally, of the 176 participants with more than 1 attack prior to study enrollment, 12.4% (n = 17) of the cohort who were treated with inebilizumab (n = 137) experienced an attack compared with 48.7% (n = 19) of the 39 individuals in the placebo group (HR, 0.212; 95% CI, 0.110-0.408). There were no reported significant differences in attacks nor in Expanded Disability Status Scale worsening between those with 1 prestudy attack and those with 2 or more prestudy attacks.1
Study investigator Bruce Cree, MD, PhD, MAS, FAAN, professor of clinical neurology, University of California, San Francisco (USCF) Weill Institute for Neurosciences, and clinical research director, UCSF Multiple Sclerosis and Neuroinflammation Center, sat down with NeurologyLive® to offer his perspective on the data, sharing his insight into the clinical takeaways and the efficacy of this new option for patients with NMOSD.
The N-MOmentum clinical trial investigated the question as to whether B-cell depletion with a monoclonal antibody directed against CD19 is effective at preventing relapses and disability in neuromyelitis optica. This study was conducted as a placebo-controlled trial and was successful. It showed that there was a highly significant effect of inebilizumab, also known as Uplizna, on preventing attacks and on the prevention of disability worsening. There are other outcomes too, such as an impact on hospitalizations and an impact on new lesions seen in central nervous system imaging by MRI, and there were significant effects there as well.
This analysis is addressing the question as to whether inebilizumab is different in individuals who’ve had a single attack—meaning patients [who have just received a diagnosis of] NMOSD—or in individuals who’ve had more than 1 attack. Those are the [patients] who have had a longer disease course. What is being shown in this poster is that inebilizumab has a very comparable effect in individuals who have had a single attack, meaning individuals [who have just been given diagnoses], compared with individuals who’ve had more than 1 attack or many attacks. It’s important for clinicians to know and understand that inebilizumab can be used in individuals who, right at the time of first attack, [have just received diagnoses], as well as in patients who have a longer disease course, and almost invariably have more treatment experience as well.
First off, it’s important to understand, in whom does the drug work? The bottom line is the drug seems to work regardless of race, regardless of age, and it works in men and women. It works regardless of number of prior attacks. Across the board, it is a very effective drug. In terms of trying to understand the applicability of a particular medication, you must look at not only the primary end point—which was an impact on acute attacks—but also some of the secondary end points.
I think one of the things that distinguishes inebilizumab from the other products that are available for treatment in NMOSD is its impact on disability. There’s a robust effect on NMO-related disability. Many [individuals] think that this is primarily driven by attacks, but there’s probably some degree of insidious worsening that occurs in NMO as well. This product has a robust effect on NMO-related disability, NMO-related attacks, NMO-related hospitalizations, and of course, MRI outcomes, which I think are very important, too.
Now, out of the different trials that have recently been conducted that led to approval of the 3 products in NMOSD, N-MOmentum was the only study that systematically used MRI as an end point. That’s important for clinicians to understand as well. Really, when you look at all these clinical and radiographic end points, all favoring line inebilizumab treatment, I think it’s fairly clear that inebilizumab has a robust effect on multiple domains of clinical and radiographic interest for clinicians.
We don’t have that high-[efficacy] vs low-efficacy conversation like we do in [multiple sclerosis], and the reason we don’t have that is because all 3 products are incredibly effective. They’re all great drugs. That’s just kind of amazing, right? We went from a state of having really nothing available to having 3 products that all have just knocked the ball out of the park in terms of efficacy. I see all of them as having a place.
There are clear differences between route of administration and frequency of infusions. So, for example, with eculizumab (Soliris; Alexion), infusions are every 2 weeks after a multiweek, initial loading dose. For inebilizumab, the infusions are twice a year. For satralizumab (Enspryng; Genentech), there are no infusions because the product is administered by subcutaneous injection at home.
Each of the drugs has a different route of administration, different frequency of either injections or infusions, and that makes questions about tolerability come into play. In addition, they have unique safety profiles. It’s essential that anybody who’s prescribing these medications not only understands their efficacy but their safety profiles as well.