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Annual European Hematology Association (EHA) Congress 2023

Updated: Jun 12, 2023

During the ALPHA Phase III trial, danicopan, an investigational oral Factor D inhibitor, demonstrated positive outcomes as an add-on treatment to Ultomiris or Soliris in patients with paroxysmal nocturnal haemoglobinuria (PNH) experiencing clinically significant extravascular haemolysis (EVH). The trial results showed a significant increase in haemoglobin levels compared to placebo from baseline to week 12.

Furthermore, all critical secondary endpoints indicated statistical superiority for danicopan. The treatment effectively reduced fatigue, anaemia, and the need for transfusions.

The ALPHA trial, a pivotal Phase III study, included patients with PNH who were already receiving standard C5 inhibitor therapy, Ultomiris or Soliris. The addition of danicopan to the treatment regimen demonstrated a significant and clinically meaningful increase in haemoglobin levels while maintaining disease control, as compared to the placebo plus established C5 inhibitor therapy.

During the prespecified interim analysis of the trial, which occurred after 63 participants completed or discontinued the primary treatment period of 12 weeks, danicopan met the primary efficacy endpoint. In patients using Ultomiris or Soliris for PNH management, the addition of danicopan resulted in superior outcomes compared to placebo plus Ultomiris or Soliris. The change in haemoglobin levels from baseline to week 12, measured by least squares mean change and standard error of the mean, was significantly greater in the danicopan group (2.94g/dL) than in the placebo group (0.50g/dL). Notably, the improvements in haemoglobin levels were observed as early as week two and sustained through week 12.

These findings highlight the potential of danicopan as an add-on therapy to Ultomiris or Soliris in improving haemoglobin levels and maintaining disease control for PNH patients.

AbbVie has presented new findings demonstrating the long-term effectiveness and safety of Venclyxto/Venclexta (venetoclax)-based combination therapies in patients with Chronic Lymphocytic Leukemia (CLL). The data from two studies highlight the sustained progression-free survival (PFS) achieved with fixed-duration venetoclax combination regimens in CLL patients across different stages of the disease.

CLL14 Long-Term Analysis

The Phase 3 CLL14 study, with a median follow-up of six years, revealed continued PFS in previously untreated CLL patients with co-existing conditions who were treated with venetoclax plus obinutuzumab. This treatment combination showed improved PFS and higher rates of undetectable minimal residual disease (uMRD) compared to the standard treatment of chlorambucil plus obinutuzumab. 53.1% of patients achieved uMRD in the venetoclax plus obinutuzumab arm compared to 21.7% in patients on chlorambucil plus obinutuzumab. There was an improvement in the rates of time to the subsequent treatment (65.2% versus 37.1%).

The patients treated with venetoclax plus obinutuzumab also had significantly higher rates of time to the subsequent treatment (TTNT) than those receiving chlorambucil plus obinutuzumab across all risk groups.

No new safety concerns were identified in the six-year analysis.

MURANO trial in relapsed/refractory CLL

The Phase 3 MURANO trial, with a final seven-year follow-up, demonstrated sustained PFS and overall survival (OS) in patients with relapsed/refractory (R/R) CLL treated with venetoclax and rituximab. The patients treated with the venetoclax-based combination showed significantly longer median PFS than those receiving bendamustine plus rituximab (54.7 months versus 17.0 months).

The seven-year OS rates were also higher in the venetoclax-based combination group (69.6% versus 51%). Most patients treated with the entire two-year venetoclax-based combination achieved uMRD, resulting in improved PFS and OS compared to those with detectable minimal residual disease.

The safety profile of the venetoclax-rituximab combination remained consistent with the known safety profile of each therapy alone. No severe new safety issues were reported in the updated analysis.

Genentech presented positive results from two Phase III studies, COMMODORE 1 and COMMODORE 2, evaluating the efficacy and safety of crovalimab in patients with paroxysmal nocturnal hemoglobinuria (PNH). Crovalimab, an investigational anti-C5 recycling monoclonal antibody, was compared to eculizumab, the current standard of care for PNH.

In the COMMODORE 2 study, crovalimab and eculizumab demonstrated similar hemolysis control rates, with 79.3% and 79.0% of participants, respectively, achieving control from week five to week 25. Transfusion avoidance was also comparable, with 65.7% of crovalimab-treated patients and 68.1% of eculizumab-treated patients achieving this outcome. Crovalimab showed a numerically more significant improvement in FACIT-Fatigue score compared to eculizumab.

The incidence of adverse events (AEs) was similar between the crovalimab and eculizumab groups, occurring in 78% and 80% of participants, respectively. Serious infections were observed in 3% of crovalimab-treated participants and 7% of eculizumab-treated participants, with no meningococcal infections.

Results from the COMMODORE 1 study indicated that crovalimab maintained disease control in patients who switched from currently approved complement inhibitors. The data supported the consistent benefit-risk profile of crovalimab and the subcutaneous administration route, including the potential for self-administration.

Preliminary data from the COMMODORE Burden of Illness study highlighted the substantial burden of disease experienced by individuals with PNH, despite available C5 inhibitor treatments. This burden negatively impacts their quality of life and results in considerable costs, suggesting the potential benefit of alternative treatment options.

Genentech announced that it plans to submit the global Phase III data from the COMMODORE 1 and 2 studies to regulatory authorities worldwide.

Vertex Pharmaceuticals and CRISPR Therapeutics announced positive results from pivotal trials of exagamglogene autotemcel (exa-cel) in transfusion-dependent beta-thalassemia (TDT) and severe sickle cell disease (SCD) patients. Both trials achieved their primary and critical secondary endpoints during pre-specified interim analyses.

The data presented at the congress included information from the ongoing Phase 3 trials (CLIMB-111 and CLIMB-121) and the long-term follow-up trial (CLIMB-131). Eighty-three patients, 48 with TDT and 35 with SCD, were dosed with exagamglogene autotemcel with follow-up up to 43.7 months.

For patients with TDT, 27 were evaluable for the primary and key secondary endpoints. Among them, 24 patients (88.9%) achieved transfusion independence for at least 12 consecutive months (TI12) and transfusion independence for at least six straight months (TI6) with a mean weighted haemoglobin of at least 9 g/dL. The mean duration of transfusion independence was 20.5 months, with a maximum of 40.7 months. The remaining three patients showed substantial reductions in transfusion volume or complete cessation of transfusions.

In patients with severe SCD, 17 were evaluable for the primary and critical secondary endpoints. Among them, 16 patients (94.1%) achieved freedom from vaso-occlusive crises (VOCs) for at least 12 consecutive months (VF12), and all 17 patients (100%) achieved independence from hospitalizations related to VOCs for at least 12 straight months (HF12). The mean duration of the VOC-free period was 18.7 months, with a maximum of 36.5 months.

The safety profile of exagamglogene autotemcel was consistent with the conditioning and transplant procedures involved.


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