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American Society of Hematology (ASH) Annual Meeting and Exposition | 2023 | iPharmaCenter

Updated: Dec 16, 2023

Novartis presented long-term data on Fabhalta in PNH patients 

Novartis has unveiled the latest findings from the Phase III APPLY-PNH trial, demonstrating the sustained effectiveness and long-term safety of Fabhalta (iptacopan) over 48 weeks in adults with paroxysmal nocturnal hemoglobinuria (PNH).

During the extension period of the APPLY-PNH trial, continuous treatment with Fabhalta in adults with PNH led to prolonged increases in haemoglobin levels, reaching near-normal values (≥12 g/dL), along with a notable reduction in the need for blood transfusions and improved patient-reported fatigue. The safety profile observed was consistent with previously reported data. 

Patients who transitioned from anti-C5 therapy to Fabhalta during the extension period achieved outcomes comparable to those in the Fabhalta arm during the initial 24-week randomized controlled period, including transfusion avoidance and the attainment of near-normal haemoglobin levels (≥12 g/dL) for the majority of patients. Recently approved by the FDA for adults with PNH, Fabhalta is now accessible for previously treated and treatment-naive patients.

Novartis reported the results from the extension period of the pivotal Phase III APPLY-PNH trial, focusing on adults with PNH experiencing residual anaemia (haemoglobin <10 g/dL) despite prior anti-C5 therapy. Continuous treatment with Fabhalta (200 mg twice daily) for 48 weeks consistently led to sustained increases in haemoglobin levels, achieving near-normal levels (12 g/dL or more), a reduced need for blood transfusions, and diminished patient-reported fatigue in the majority of patients. 

Similar benefits were observed in patients who switched from anti-C5 therapy to Fabhalta during the extension period. Patients who completed the initial 24-week randomized treatment period of APPLY-PNH had the option to enter the extension, continuing with Fabhalta (61 out of 62 patients; one patient discontinued due to pregnancy) or switching from anti-C5s to Fabhalta (34 out of 35 patients; one patient discontinued based on investigator decision) through week 48.


In the continuous Fabhalta group, the positive outcomes achieved during the randomized period persisted at 48 weeks. The mean haemoglobin level remained near-normal (12.2 g/dL), nearly all patients (91.9%) remained free of transfusions (Weeks 2-48), and improvements in patient-reported fatigue were observed (adjusted mean change from baseline: 9.80-point increase in Functional Assessment of Chronic Illness Therapy – Fatigue [FACIT-F] score). In the anti-C5-to-Fabhalta group, similar benefits emerged after the switch, with mean haemoglobin levels reaching near-normal values (from 9.1 g/dL at 24 weeks to 12.1 g/dL at 48 weeks), transfusion avoidance achieved for almost all patients (94.1%, Weeks 26-48), and improvements in patient-reported fatigue observed after transitioning to Fabhalta (adjusted mean change from baseline between Week 48 and Week 24: 10.79-point increase in FACIT-F score).


The safety profile of Fabhalta at 48 weeks was comparable to that at 24 weeks, with three patients experiencing major adverse vascular events (MAVEs), all deemed unrelated to Fabhalta.


Abecma demonstrated superior data vs standard therapy in earlier lines of multiple myeloma treatment 

Bristol Myers Squibb and 2seventy Bio, Inc. released findings from the final progression-free survival (PFS) analysis of the KarMMa-3 study, a Phase 3 trial comparing Abecma (idecabtagene vicleucel) with standard regimens in adults with relapsed and refractory multiple myeloma. After a median follow-up of over 30 months, Abecma demonstrated a sustained 51% reduction in the risk of disease progression or death, boasting a median PFS of 13.8 months, compared to 4.4 months for standard regimens.


Abecma showcased significantly improved responses, with a complete response rate of 44% versus 5% for standard regimens, and these benefits persisted across various patient subgroups. The safety profile of Abecma in the KarMMa-3 study remained consistent, with predictable and mostly low-grade occurrences of cytokine release syndrome and neurotoxicity.

In newly diagnosed multiple myeloma, Abecma demonstrated deep and durable responses, achieving a 77% complete response rate with a median PFS not reached, and no new safety signals were identified in the extended follow-up from the KarMMa-2 study.

The study's patient-centric design allowed crossover from standard regimens to Abecma upon confirmed disease progression. In terms of overall survival (OS), Abecma exhibited a median OS of 41.4 months, compared to 37.9 months for standard regimens, with a positive trend observed in sensitivity analyses adjusting for crossover. The predefined sensitivity analyses, which accounted for crossover, revealed a median overall survival (OS) of 41.4 months for Abecma, surpassing the 23.4 months observed for standard regimens. These findings indicate a favorable trend in OS benefit for Abecma when compared to standard regimens.

Abecma's safety profile, including low-grade occurrences of CRS and neurotoxicity, remained consistent with extended follow-up, reinforcing its well-established nature. Notably, Abecma recently received regulatory approval in Japan for patients with relapsed or refractory multiple myeloma, further solidifying its position as the first CAR T cell therapy to receive approval for use in earlier lines of therapy. The results are currently under review with the U.S. FDA, and regulatory applications are also pending in Europe.

Extended follow-up results for Cohort 2c of the KarMMa-2 study revealed promising outcomes, with Abecma showcasing an 87.1% overall response rate and a 77.4% complete response rate in patients with inadequate responses to frontline therapy.

Abecma, the first-in-class BCMA-directed CAR T cell therapy, holds FDA approval for the treatment of adult patients with relapsed or refractory multiple myeloma after four or more prior lines of therapy, establishing its significance in the evolving landscape of multiple myeloma treatment.


Darzalex Faspro quadruplet therapy significantly improves outcomes in transplant-eligible newly diagnosed multiple myeloma patients

Johnson & Johnson has disclosed the initial results from the PERSEUS Phase 3 study, showcasing significant clinical advancements through a quadruplet induction, consolidation regimen, and doublet maintenance regimen based on Darzalex Faspro (daratumumab and hyaluronidase) for transplant-eligible (TE) individuals with newly diagnosed multiple myeloma (NDMM). The findings from this Phase 3 study evaluating TE NDMM reveal an unprecedented progression-free survival (PFS) and substantial enhancements in rates of overall complete response (CR) or better and minimal residual disease (MRD) negativity compared to the comparator arm.

Conducted collaboratively with the European Myeloma Network, the PERSEUS study demonstrates that induction and consolidation treatment with Darzalex Faspro in combination with bortezomib, lenalidomide, and dexamethasone (D-VRd), followed by Darzalex Faspro and lenalidomide (D-R) maintenance, results in a 58% reduction in the risk of disease progression or death compared to bortezomib, lenalidomide, and dexamethasone (VRd) alone followed by lenalidomide (R) maintenance. Furthermore, the quadruplet regimen significantly deepens the treatment response compared to VRd alone, with increased rates of CR or better, stringent complete response (sCR), and MRD negativity.

The estimated 48-month PFS rates were 84.3% for D-VRd vs 67.7% for VRd. Treatment with D-VRd also led to deeper responses compared with VRd, including higher rates of sCR (69.3% vs 44.6%), and ≥CR (87.9% vs 70.1%). MRD negativity rates (10–5) were higher with D-VRd vs VRd (75.2% vs 47.5%). Sustained MRD-negativity rates (for ≥12 months) more than doubled with D-VRd (64.8% vs 29.7%). Overall survival (OS) data are not yet mature but are showing favourable trends for the D-VRd arm compared to VRd.

The overall safety profile of D-VRd was consistent with the known safety profiles for daratumumab and VRd. The most common (>10%) Grade 3/4 hematologic and non-hematologic adverse events (AE) with D-VRd vs VRd were neutropenia (62.1% vs 51.0%), thrombocytopenia (29.1% vs 17.3%), diarrhoea (10.5% vs 7.8%), pneumonia (10.5% vs 6.1%), and febrile neutropenia (9.4% vs 10.1%).


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