Drug Name:danicopan

R&D Code:ACH-4471

CAS:1903768-17-1

Original Research Company:Achillion Pharmaceuticals; AstraZeneca 

2024Year4Month1Day,VOYDEYA™(danicopan)Has been approved in the United States asravulizumabOreculizumabAdditional therapy for the treatment of adult paroxysmal nocturnal hemoglobinuria(PNH)Extravascular Hemolysis(EVH)。

The approval of the U.S. Food and Drug Administration is based on the keyALPHA IIIPositive results from the Phase trial. The trial lasted12The results of Zhou's preliminary evaluation period were published in The Lancet Haematology.

ALPHA IIIThe trial period evaluatedVOYDEYAAsULTOMIRISOrSOLIRISAdditional TherapyPNHWith clinical significanceEVHThe efficacy and safety of patients. The results showed that from baseline to day12Week,voydeyaReached the primary endpoint of hemoglobin change and all keyThe secondary endpoints, including transfusion avoidance and changes in the Functional Assessment of Chronic Illness Therapy-Fatigue Score.

ALPHA IIIResults from the trial period showed,voydeyaOverall Tolerability Was Good, with No New Safety Issues Identified. The most common treatment-related adverse events in the trial were headache, nausea, arthralgia, and diarrhea.

Earlier,voydeyaHas been approved by the United StatesFDAGranted Breakthrough Therapy Designation and awarded Priority Medicine status by the European Medicines Agency.voydeyaHas also been approved for treatment in the United States, the European Union, and Japan.PNHOrphan Drug Designation.VOYDEYAHas been approved in Japan (2024Year1Month19Day), and recommended EU approval. Other countries are conducting regulatory reviews.

ALPHAIs a key globalIIIPhase clinical trial, aimed at evaluatingVOYDEYAAsC5Add-on Medications for Inhibitor TherapySOLIRISOrULTOMIRISClinically SignificantEVHThePNHEfficacy and safety in patients. In this double-blind, placebo-controlled, multi-dose trial, patients were enrolled and randomly assigned to receiveVOYDEYAOrPlacebo(2:1), while receiving continuous12Week'sSOLIRISOrULTOMIRISTreatment. As of2022Year6Month28Day,63Name Randomized Patients Completed12Pre-specified interim analysis was conducted during the initial evaluation period of the week or after discontinuation of treatment.12Weeks, Placebo+ SOLIRISOrULTOMIRISThe group of patients was converted toVOYDEYA+  SOLIRISOrULTOMIRISGroup, andVOYDEYA+ SOLIRISOrULTOMIRISThe group of patients continued to receive this treatment.12Week. Complete two treatment periods(24Week)Patients can choose to participate in a two-year long-term extension period, and inSOLIRISOrULTOMIRISContinue to accept outsideVOYDEYATreatment. The open-label period of the study is currently ongoing.

Mechanism of Action

Danicopan prevents the cleavage of complement factor B into Ba and Bb fragments, which are necessary for the formation of the alternative pathway complement component C3 convertase (C3bBb), the production of downstream effectors (including opsonization by C3 fragments), and the amplification of the terminal pathway. In paroxysmal nocturnal hemoglobinuria, danicopan acts proximally in the alternative pathway of the complement cascade, preferentially controlling extravascular hemolysis mediated by C3 fragments, while co-administration of ravulizumab or eculizumab is expected to control intravascular hemolysis mediated by MAC.

Key Intermediate Synthesis

WO2017035409