Satralizumab

In neuromyelitis optica spectrum disorder, Ultomiris’ current competitors include Roche’s Enspryng and Amgen’s Uplizna. (AstraZeneca) 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.

Pictured: Roche's building in Shanghai, China/iStock, Robert Way Roche subsidiary Chugai Pharmaceutical on Thursday unveiled results from the Phase III LUMINESCE study, showing that its IL-6 inhibitor Enspryng (satralizumab) could significantly improve generalized myasthenia gravis symptoms that affect daily life. However, the biotech was unsatisfied with the magnitude of Enspryng’s effects, noting in the announcement that “the results did not reach our expectations on the degree of clinical benefit.” In terms of safety, LUMINESCE found that Enspryng was well-tolerated when used to treat generalized myasthenia gravis (gMG), with an adverse event pro was consistent with what had been established in trials in neuromyelitis optica spectrum disorder (NMOSD). Roche and Chugai did not provide specific data in their announcement but promised to present detailed results at the upcoming American Academy of Neurology Annual Meeting on April 15 in Denver, Colorado. The companies also did not detail their future plans for Enspryng in gMG, a chronic autoimmune disorder in which antibodies destroy communication between nerves and muscle, causing weakness of the skeletal muscles. Designed to be delivered via subcutaneous Injections, Enspryng is a recombinant humanized monoclonal antibody that targets the IL-6 cytokine. According to its label, Enspryng’s exact mechanism of action is still unknown, though it is thought to Interfere with IL-6 signaling and the inflammatory cascade. Enspryng won the FDA’s approval in August 2020 for the treatment of NMOSD patients positive for the aquaporin-4 antibody. Thursday’s readout does not affect Enspryng’s approval in NMOSD, according to the companies’ announcement. Roche and Chugai will also continue to develop Enspryng in other inflammatory and neurological autoimmune indications, including myelin oligodendrocyte glycoprotein-associated disorder, thyroid eye disease and autoimmune encephalitis. LUMINESCE’s disappointing data buck Roche’s clinical winning streak in recent months. Last week, the pharma announced during a neurology-focused investor event that its investigational Alzheimer’s disease therapy trontinemab cleared a Phase Ib/II study, demonstrating rapid and robust reduction in amyloid plaque levels. Trontinemab, developed using Roche’s proprietary Brainshuttle technology, penetrates the blood-brain barrier reaching high levels of distribution throughout the central nervous system. Earlier this month, Roche’s Alnylam-partnered RNAi therapeutic zilbesiran aced its Phase II study, eliciting a significant drop in 24-hour mean systolic blood pressure. Roche also recently reported several Phase III victories, including one for its asthma drug Xolair (omalizumab) in food allergies and its anti-TIGIT immunotherapy tiragolumab in esophageal squamous cell carcinoma. In December 2023, the pharma announced that its orally available PI3Kα inhibitor inavolisib significantly improved progression-free survival in PIK3CA-mutated, HER2-negative breast cancer when used with palbociclib and fulvestrant in the first-line setting. Tristan Manalac is an independent science writer based in Metro Manila, Philippines. Reach out to him on LinkedIn or email him at tristan@tristanmanalac.com or tristan.manalac@biospace.com.