Nearly five years after an FDA approval for Soliris in neuromyelitis optica spectrum disorder (NMOSD), AstraZeneca’s follow-on C5 drug Ultomiris has entered the rare neurological disease, as well.
The FDA has cleared Ultomiris for patients with anti-AQP4 antibody-positive NMOSD, which by AZ’s estimates constitutes about 75% of all NMOSD cases.
Compared with Soliris, Ultomiris reduces the dosing frequency from biweekly infusions to once every eight weeks during the maintenance phase. AZ has been hoping that Ultomiris’ long-acting nature could help it reach more patients with various autoimmune diseases.
The NMOSD nod came later than expected. The FDA first rejected Ultomiris in the indication in September, requesting AZ to modify the design of a mandated safety monitoring program known as a Risk Evaluation and Mitigation Strategy.
In NMOSD, Ultomiris’ current competitors include Roche’s Enspryng, a once-monthly injection that can be self-administered; and Amgen’s Uplizna, which is an infusion that can be given every six months.
NMOSD is a rare chronic autoimmune disorder of the central nervous system affecting about 200,000 people worldwide. It’s more common in women beginning in their 30s and 40s.
Ultomiris proved its worth in NMOSD in the phase 3 CHAMPION-NMOSD trial. In the study, no patients experienced an adjudicated relapse by the time the last enrolled participant completed their 50-week visit, or after a median treatment duration of 73 weeks. Compared to external control, Ultomiris led to a 98.6% reduction in the risk of relapse.
By comparison, 89% of anti-AQP4 antibody-positive patients who took Amgen’s Uplizna in the N-MOmentum trial remained relapse-free during a six-month period. For Roche’s Enspryng, the relapse-free rate at 96 weeks was 76.5% in the SAKuraStar monotherapy study and 91.1% in the SAkuraSky study, in which patients also received baseline immunosuppressant therapy.
With Ultomiris, AZ now offers a treatment option that has the potential to eliminate relapses with a dosing schedule every eight weeks, Marc Dunoyer, CEO of AZ’s Alexion rare disease unit, said in a statement Monday.
First approved by the FDA in late 2018, Ultomiris is also allowed in multiple other autoimmune diseases, including generalized myasthenia gravis (gMG) thanks to a 2022 approval. Roche last week just reported a positive phase 3 trial for Enspryng in gMG but said the size of clinical benefit didn’t meet the company’s expectations.
With just the NMOSD label, Enspryng brought Roche 256 Swiss francs ($285 million) in sales in 2023. And Uplizna, a key asset that Amgen brought as part of its $27.8 billion acquisition of Horizon Therapeutics, generated $65 million in sales last year after an FDA NMOSD nod in mid-2020. A phase 3 readout for Uplizna in myasthenia gravis is expected in the second half of this year.
Thanks to its multiple indications, Ultomiris reeled in nearly $3 billion in sales last year, up 51% year over year, although some of the growth came at the cost of Soliris.
AZ is not done expanding Ultomiris. Two phase 3 trials are testing the long-acting C5 inhibitor in hematopoietic stem cell transplant-associated thrombotic microangiopathy and cardiac surgery-associated acute kidney injury. AZ believes both diseases hold blockbuster opportunities.
Besides those studies, midphase trials are underway in lupus nephritis and immunoglobulin A nephropathy. The British pharma suffered a setback recently as it canned a phase 2 trial for Ultomiris in dermatomyositis due to disappointing efficacy.