Eculizumab

Dosing is central to Dianthus Therapeutics\' plans to differentiate its candidate in a competitive market. \n Dianthus Therapeutics is advancing its challenge for the increasingly competitive generalized myasthenia gravis (gMG) market, outlining plans to move into phase 3 on the back of hits in a midphase study.The phase 2 trial compared two doses of claseprubart, an antibody engineered to selectively target the classical pathway, to placebo in 65 adults with AChR-positive gMG. Patients received claseprubart every two weeks via subcutaneous injection. While the primary endpoint looked at safety and tolerability, the secondary endpoint data provided a glimpse of the efficacy of the drug candidate. At the low dose, Dianthus reported a 4.6-point improvement on MG-ADL, a scale that measures the impact of gMG on daily functions. The improvement rose to 5.4 points on the high dose. Adjusted for placebo, the improvements on the low and high doses were 1.8 points and 2.6 points, respectively.Dianthus shared the results alongside data on QMG, a physician\'s score of disease severity. QMG scores improved 4.4 points and 4.5 points, respectively, on the low and high doses. Scores improved by two points in the placebo arm. Dianthus also reported statistically significant improvements on other measures of gMG. The biotech shared cross-trial comparisons to show how claseprubart performed against AstraZeneca’s Soliris and Ultomiris and UCB’s Zilbrysq. Claseprubart outperformed the competition in the data shared by Dianthus, with the caveat that such cross-trial comparisons can be unreliable. The company found the drug candidate was generally well tolerated, giving it a data set to inform talks with the FDA and preparations for phase 3. Dianthus plans to test two regimens of the low dose in phase 3, with patients receiving the study drug every two or four weeks. Dianthus didn’t test four-week dosing in the phase 2 study, but the lack of statistical difference between the low and high doses, coupled with evidence such as half-life data, led it to speculate that a less-frequent regimen could work. The two-week dose is Dianthus’ target product profile, but CEO Marino Garcia sees an opportunity to go beyond the base case.“Why not go further? Why not push that differentiation? I don\'t see much of a downside to be honest,” Garcia said on a call with investors to discuss the data. Dosing is central to Dianthus’ plans to differentiate its candidate in a competitive market. The company said more than 80% of patients with AChR-positive gMG have yet to switch to a biologic, despite the availability of C5 inhibitors such as Ultomiris and FcRn drugs, including argenx’s Vyvgart. Dianthus has identified intravenous and high-volume subcutaneous dosing as a barrier to uptake of rival drugs.That thinking led Dianthus to develop an autoinjector. The overarching goal is to combine the efficacy of C5 inhibitors such as Ultomiris with the safety of C1 blockers such as Enjaymo and the convenience of Dupixent. Analysts at Evercore ISI said in a note to clients that: “Both doses clearly met all the bull case efficacy bars” the firm had discussed in preview ahead these data. They added that the biotech “convincingly” matched the C5s. It didn’t see a dose response, thus “opening the door to a longer Q4W dosing interval.”

iStock, beast01 Regeneron’s cemdisiran, used alone or in combination with its complement inhibitor Veopoz, significantly improved activities of daily living in patients with generalized myasthenia gravis.   Regeneron’s investigational small interfering RNA therapy cemdisiran significantly improved disease activity in certain patients with generalized myasthenia gravis, opening up a path for regulatory filing early next year. Results from the Phase III NIMBLE study were published Tuesday , demonstrating a 2.3-point placebo-adjusted improvement in Myasthenia Gravis Activities of Daily Living (MG-ADL) scores, a patient-reported scale used to measure the daily impacts of the disease. Cemdisiran also achieved a 74% reduction of complement factor 5 (C5), a part of the complement system that is inappropriately activated in gMG. Regeneron also tested a combination regimen of cemdisiran with the company’s complement inhibitor Veopoz, which elicited a significant MG-ADL improvement of 1.74 points over placebo. Veopoz is approved for the treatment of patients 1 year and up with CD55-deficient protein-losing enteropathy. In premarket trading Wednesday, Regeneron’s stock was up 2.67%. Writing to investors on Tuesday, analysts at Truist Securities noted that cemdisiran  monotherapy  “surpassed our expectations,” given the “historical performance” of other anti-C5 therapies. NIMBLE did not detect instances of meningitis, a known side effect of this drug class, but Truist still expects cemdisiran to come with a boxed warning if approved, “based on the class precedent.” Aside from its apparent efficacy and safety edge, Truist also pointed to cemdisiran’s “convenient administration” as another point for Regeneron. The drug is given subcutaneously every 12 weeks, whereas its most notable competitors—AstraZeneca’s Soliris and Ultomiris—are delivered intravenously. This administration advantage could help cemdisiran “capture a significant share of the C5 gMG market,” according to the analysts. With NIMBLE data in hand, Regeneron is planning an FDA submission for the first quarter of 2026, the pharma noted in its Tuesday release. Full findings from the study will be shared at an upcoming meeting. Designed to target and destroy C5 mRNA, cemdisiran is a small interfering RNA therapy that helps suppress the complement cascade, which in gMG plays a role in damaging muscle nerves. The therapy was developed by Alnylam as part of a research collaboration with Regeneron, for which Regeneron in April 2019 paid $800 million upfront . The deal gave the pharma access to Alnylam’s RNAi experience for diseases of the eyes and central nervous system, a push that has cemdisiran at its core. Milestone payments for this agreement could reach up to $200 million. Elsewhere in the gMG arena, argenx on Monday reported positive Phase III data for its FcRn inhibitor Vyvgart, positioning it up for expansion into patients who are AChR seronegative. While argenx did not provide specific data, it emphasized a “statistically significant and clinically meaningful improvement” in disease activity in patients treated with Vyvgart, adding that it is preparing for a label expansion application into this specific patient population.