Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Label indication VOYDEYA is indicated as add-on therapy to ravulizumab or eculizumab for the treatment of extravascular hemolysis (EVH) in adults with paroxysmal nocturnal hemoglobinuria (PNH). VOYDEYA is a complement factor D inhibitor indicated as add-on therapy to ravulizumab or eculizumab for the treatment of extravascular hemolysis (EVH) in adults with paroxysmal nocturnal hemoglobinuria (PNH) ( 1 ).
Also known as [14C]-Danicopan, Danicopan - Tablet, Danicopan: Powder-In-Capsule 1, Danicopan:In- 1, ALXN2040, ACH-4471, ACH-0144471 (formerly), ACH-0144471
Danicopan · 9 trials · 10 indications
Baseline was defined as the lowest Hgb value observed between and including Screening and Day 1. The least square (LS) mean and standard error (SE) were produced using mixed-effect model for repeated measures (MMRM). Hgb values collected within 4 weeks after transfusion were not included in the MMRM.
The composite biopsy score was based on a score incorporating changes in the activity index, glomerular C3c staining, and glomerular macrophage infiltration at the end of 6 months of treatment. The composite renal biopsy index scoring system ranged from 0 to 21, with higher scores indicating worse outcomes.
Proteinuria reduction was defined as ≥ 30% decrease from baseline based on 24-hour urine protein (mg/day).
Serum C3 levels were measured by conventional Roche immunoturbidimetric assay method. Change from Baseline = Serum C3 levels on Day 15 - Baseline Serum C3 levels
Plasma Intact C3 level were measured by a novel multiplex assay method. Change from Baseline = Plasma Intact C3 levels on Day 15 - Baseline Plasma Intact C3 levels
Change from Baseline = Serum LDH levels at Week 25 - Baseline Serum LDH levels. Baseline was the baseline value from the primary Study ACH471-100.
Change from Baseline = Hgb levels at Week 25 - Baseline Hgb levels. Baseline was the baseline value from the primary Study ACH471-100.
Change from Baseline = reticulocyte count at Week 25 - Baseline reticulocyte count. Baseline was the baseline value from the primary Study ACH471-100.
The PNH clone size refers to the percentage of PNH-affected cells versus normal cells within the total cell population. Change from Baseline = PNH clone size at Week 25 - Baseline PNH clone size. Baseline was the baseline value from the primary Study ACH471-100.
Serum AP functional activity was measured by the Wieslab functional immunoassay method. Change from Baseline = Serum AP functional activity at Week 25 - Baseline Serum AP functional activity. Baseline was the baseline value from the primary Study ACH471-100.
Change from Baseline = free Hgb at Week 25 - Baseline free Hgb. Baseline was the baseline value from the primary Study ACH471-100.
An AE was as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An SAE was an AE that met at least 1 of the following criteria: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization for the AE, persistent or significant disability/incapacity or substantial disruption of the ability to conduct normal life functions, congenital anomaly/birth defect (in the child of a participant who was exposed to the study drug), important medical event or reaction. The intensity of an AE was graded according to the Common Terminology Criteria for Adverse Events (CTCAE) Adverse Event Severity Grading Table. A summary of all Serious Adverse Events and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section.
Change from Baseline = Serum LDH levels on Day 28 - Baseline Serum LDH levels.
| Arm | Type | Description |
|---|---|---|
| Danicopan | EXPERIMENTAL | Participants will receive a 12-week weight-based open-label treatment period and up to 1 year open-label long term extension period. |
| Danicopan + C5 Inhibitor | EXPERIMENTAL | Participants will receive danicopan, in addition to their C5 inhibitor therapy, for 24 weeks (12 weeks in Treatment Period 1, followed by 12 weeks in Treatment Period 2). |
| Placebo + C5 Inhibitor | PLACEBO_COMPARATOR | Participants will receive placebo, in addition to their C5 inhibitor therapy, for 12 weeks during Treatment Period 1. At Week 12, participants randomized to receive placebo will be switched to danicopan for an additional 12 weeks (Treatment Period 2). |
| Danicopan (Double-blind Treatment Period), Followed by Danicopan (Open-label Extension Period) | ACTIVE_COMPARATOR | Danicopan was administered at a starting dose of 100 milligrams (mg) 3 times daily (TID) for the first 2 weeks, then dosage was to be increased to 200 mg TID for the remainder of the 6-month treatment period. All participants who completed the double-blind treatment period were enrolled in the open-label extension period and were to receive danicopan 200 mg TID. |
| Placebo (Double-blind Treatment Period), Followed by Danicopan (Open-label Extension Period) | PLACEBO_COMPARATOR | Placebo was administered TID during the 6-month treatment period. All participants who completed the double-blind treatment period were enrolled in the open-label extension period and were to receive danicopan 200 mg TID. |
| Group 1: 100 mg Danicopan TID + Eculizumab | EXPERIMENTAL | Starting dose of 100 mg danicopan TID in combination with eculizumab. |
| Group 2: Initial dose 100 or 150 mg Danicopan TID + Eculizumab | EXPERIMENTAL | Starting dose of 100 or 150 mg danicopan TID in combination with eculizumab. |
| Group 3: Initial dose of 100, 150, or 200 mg Danicopan TID + Eculizumab | EXPERIMENTAL | Starting dose of 100, 150, or 200 mg danicopan TID in combination with eculizumab. |
| Group 4: Optimal Dose of Danicopan TID + Eculizumab | EXPERIMENTAL | Optimal dose (starting dose of either 100, 150, or 200 mg, as determined from Groups 1-3) of danicopan TID in combination with eculizumab. |
| Group 1: Danicopan 100 mg TID (Sentinel) | EXPERIMENTAL | All participants received 100 milligrams (mg) of danicopan three times per day (TID) during the Treatment Period. |
| Group 2: Danicopan up to 200 mg TID | EXPERIMENTAL | All participants received not more than 200 mg of danicopan TID depending on the available safety, pharmacokinetic, and pharmacodynamic data from Group 1 (Sentinel) during the Treatment Period. |
| ACH-0144471 | EXPERIMENTAL | All participants will receive ACH-0144471 during the treatment period. |
| Part 1: Healthy Match | EXPERIMENTAL | Single 200-milligram (mg) dose of danicopan on Day 1 in healthy participants (matched control group with normal hepatic function). |
| Part 1: Moderate HI | EXPERIMENTAL | Single 200-mg dose of danicopan on Day 1 in participants with moderate HI. |
| Name | Type | Description |
|---|---|---|
| Danicopan | DRUG | Participants will receive danicopan on a weight-based dosing regimen. |
| Placebo | DRUG | Oral tablet |
| C5 Inhibitor | DRUG | Participants will continue to receive their ongoing C5 inhibitor (eculizumab or ravulizumab) therapy according to their usual dose and schedule. |
| Eculizumab | DRUG | Participants received intravenous eculizumab administered at the participant's usual dose and schedule. |
| ACH-0144471 | DRUG | ACH-0144471 will be administered to all participants enrolled in the study. |
Inclusion Criteria: * Confirmed diagnosis of PNH. * CS-EVH defined by: Anemia: Hgb ≤ 11.0 g/dL, and absolute reticulocyte count ≥ 100 × 109/L * Treated with ravulizumab or eculizumab for at least 12 weeks immediately preceding Day 1, the dose received should be stable during this period, and there ...
Danicopan is an investigational small molecule developed by AstraZeneca PLC (ticker AZN). It is being studied in nephrology and hematology indications, including C3 glomerulonephritis, C3 glomerulopathy, hepatic impairment, and paroxysmal nocturnal hemoglobinuria (PNH). It is a complement factor D inhibitor and is not yet approved.
Danicopan is being studied for paroxysmal nocturnal hemoglobinuria (PNH), including as an add-on to C5 inhibitors in patients with clinically significant extravascular hemolysis. It is also being evaluated in C3 glomerulonephritis, C3 glomerulopathy, and hepatic impairment. These uses remain investigational and are not approved.
Danicopan targets complement factor D (CFD) and acts as an inhibitor. By inhibiting factor D, it is designed to modulate the alternative complement pathway, which is relevant to conditions such as PNH and C3 glomerulopathy where complement dysregulation plays a role.
Danicopan is developed by AstraZeneca PLC, which trades under the ticker AZN. AstraZeneca is the sponsor of the clinical trials evaluating danicopan across its studied indications.
Danicopan is in Phase 2 development overall, with Phase 3 trials also conducted in paroxysmal nocturnal hemoglobinuria. It is investigational and not approved. Five trials are recorded in total, of which two are active and three are completed, with 194 participants enrolled across them.
Danicopan trials include NCT06449001, a recruiting Phase 3 study in pediatric PNH patients with extravascular hemolysis, and NCT05389449, an active Phase 3 long-term safety and efficacy study as an add-on to C5 inhibitors in PNH. Completed trials include NCT04469465 (ALPHA) in PNH and NCT03555539 in hepatic impairment.
Yes, [14C]-Danicopan is an alternative name for danicopan, along with Danicopan - Tablet, Danicopan: Powder-In-Capsule 1, and Danicopan:In- 1. These refer to the same investigational compound developed by AstraZeneca.