Skip to main content

The majority of patients taking FABHALTA experienced Hb improvements in the absence of RBC transfusions

.

PRIMARY END POINT


Patients with sustained Hb increase of ≥2 g/dL* from baseline in the absence of RBC transfusions after 24 weeks1

Response rate 77.5% FABHALTA (n=31/40; 95% CI, 61.5-89.2)

*Assessed between Days 126 and 168.1   
Assessed between Days 14 and 168. Requiring RBCs refers to any patient receiving transfusions or meeting protocol-defined criteria.

Higher Hb levels in the absence of RBC transfusions are within reach1 
                         

FABHALTA is the first PNH treatment to evaluate a primary end point of the response rate of patients achieving sustained Hb increase of ≥2 g/dL, as opposed to Hb stabilization1,3-5

Patients taking FABHALTA experienced an increase in adjusted mean Hb level of +4.29 g/dL from baseline

ADDITIONAL END POINTS

Patients experienced increases in mean Hb by Week 1, with increases through Week 246,7

Mean Hb levels (g/dL) through Week 24 (values within 30 days of transfusion are considered missing) 

Fabhalta (n=40). +4.29 g/dL (95% CI, 3.86-4.72) adjusted mean increase in Hb from baseline. Adjusted mean assessed between Weeks 18 and 24 values within 30 days after transfusion were excluded from the analysis.

The data from this additional analysis are exploratory; therefore, not subject to family-wise Type 1 error control, and presented for observation only. No formal conclusions can be made.

Click on image to enlarge. 

Sustained Hb level of ≥12 g/dL* in the absence of RBC transfusions after 24 weeks was observed in 47.5% of patients (n=19/40; 95% CI, 31.5-63.9)6

*Assessed between Days 126 and 168.1         
Assessed between Days 14 and 168. Requiring RBCs refers to any patient receiving transfusions or meeting protocol-defined criteria.2 

RBC transfusion avoidance with FABHALTA over the 24-week treatment period

ADDITIONAL END POINT

The data from this additional analysis are exploratory; therefore, not subject to family-wise Type 1 error control, and presented for observation only. No formal conclusions can be made.

Patients achieving RBC transfusion avoidance assessed between Weeks 2 and 246

Click on image to enlarge. 

In the 6 months before trial enrollment, 70% (n=28/40) of patients required a transfusion.2 Transfusion avoidance in APPOINT was defined as absence of administration of packed-RBC transfusions between Days 14 and 168.6

The impact of FABHALTA on LDH and ARC levels

ADDITIONAL END POINTS     

The data from this additional analysis are exploratory; therefore, not subject to family-wise Type 1 error control, and presented for observation only. No formal conclusions can be made.

Absolute reticulocyte count (ARC) and lactate dehydrogenase (LDH) are 2 of the known biomarkers of hemolytic activity. ARC is a marker of both IVH and EVH, while LDH primarily reflects IVH.9-11     
 

Adjusted mean change from baseline in LDH2,6,II

Click on image to enlarge.

IIMean of visits between Days 126 and 168.2  
#Day 7.2         
Day 14.2         
**Day 168.2     
 

Adjusted mean change from baseline in ARC2,6,II 

Click on image to enlarge.

IIMean of visits between Days 126 and 168.2

With FABHALTA, the adjusted mean change from baseline in FACIT-Fatigue score was +10.8

ADDITIONAL END POINT

Patient-reported FACIT-Fatigue scores may be an underestimation or overestimation because patients were not blinded to treatment.

The data from this additional analysis are exploratory; therefore, not subject to family-wise Type 1 error control, and presented for observation only. Due to the explanatory nature, small sample size, single-arm and open-label design, no formal conclusions can be made.

  • Assessed between Weeks 18 and 24. The adjusted mean change* from baseline in FACIT-Fatigue score†† in patients taking FABHALTA was +10.8 (95% CI, 8.63-12.95)2,6

Click on image to enlarge.

  • In separate large-scale surveys, the mean FACIT-Fatigue score for the general population was 4412,13,§§

*Assessed between Days 126 and 168.1
††The Functional Assessment of Chronic Illness Therapy – Fatigue Scale (FACIT-Fatigue) is a 13-item questionnaire that assesses self-reported fatigue and its impact upon daily activities and function. The level of fatigue is measured on a 4-point Likert scale (in the study, 4=not at all fatigued to 0=very much fatigued), with 0 being the worst possible score and 52 the best.2        
‡‡Baseline mean FACIT-Fatigue scores and adjusted mean change in FACIT-Fatigue scores at Day 168 were reported for 40 patients.2  
§§The FACIT-Fatigue score for the general population was determined through the assessment of 1010 adults in the US in 2002 and 2426 adults in Germany in 2018.12,13

Start adult patients on FABHALTA

IMPORTANT SAFETY INFORMATION

WARNING: SERIOUS INFECTIONS CAUSED BY ENCAPSULATED BACTERIA

FABHALTA, a complement inhibitor, increases the risk of serious infections, especially those caused by encapsulated bacteria, such as Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae type B. Life-threatening and fatal infections with encapsulated bacteria have occurred in patients treated with complement inhibitors. These infections may become rapidly life-threatening or fatal if not recognized and treated early.

  • Complete or update vaccinations for encapsulated bacteria at least 2 weeks prior to the first dose of FABHALTA, unless the risks of delaying therapy with FABHALTA outweigh the risk of developing a serious infection. Comply with the most current Advisory Committee on Immunization Practices (ACIP) recommendations for vaccinations against encapsulated bacteria in patients receiving a complement inhibitor.

  • Patients receiving FABHALTA are at increased risk for invasive disease caused by encapsulated bacteria, even if they develop antibodies following vaccination. Monitor patients for early signs and symptoms of serious infections and evaluate immediately if infection is suspected.

Because of the risk of serious infections caused by encapsulated bacteria, FABHALTA is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the FABHALTA REMS.

INDICATION

FABHALTA is indicated for the treatment of adults with paroxysmal nocturnal hemoglobinuria (PNH).

CLICK OR SCROLL TO SEE IMPORTANT SAFETY INFORMATION, INCLUDING BOXED WARNING AND INDICATION

Definitions  
ARC, absolute reticulocyte count; CI, confidence interval; EVH, extravascular hemolysis; FACIT-Fatigue, Functional Assessment of Chronic Illness Therapy-Fatigue; HB, hemoglobin; IVH, intravascular hemolysis; LDH, lactate dehydrogenase; PNH, paroxysmal nocturnal hemoglobinuria; RBC, red blood cell; ULN, upper limit of normal.

References  
1. Fabhalta. Prescribing information. Novartis Pharmaceuticals Corp.  
2. Data on file. Study CLNP023C12301 CSR. Novartis Pharmaceuticals Corp; 2022.  
3. Empaveli. Prescribing information. Apellis Pharmaceuticals, Inc.  
4. Soliris. Prescribing information. Alexion Pharmaceuticals, Inc.  
5. Ultomiris. Prescribing information. Alexion Pharmaceuticals, Inc.  
6. Data on file. Study CLNP023C12301 and Study CLNP023C12302 supporting analyses for USPI clinical efficacy section. Novartis Pharmaceuticals Corp; 2023.  
7. Data on file. Study CLNP023C12302 FIR. Novartis Pharmaceuticals Corp; 2022.  
8. Cappellini MD, Motta I. Anemia in clinical practice—definition and classification: does hemoglobin change with aging? Semin Hematol. 2015;52(4):261-269. doi:10.1053/j.seminhematol.2015.07.006  
9. Brodsky RA. Paroxysmal nocturnal hemoglobinuria. Blood. 2014;124(18):2804-2811. doi:10.1182/blood-2014-02-522128  
10. Risitano AM, Notaro R, Marando L, et al. Complement fraction 3 binding on erythrocytes as additional mechanism of disease in paroxysmal nocturnal hemoglobinuria patients treated by eculizumab. Blood. 2009;113(17):4094-4100. doi:10.1182/blood-2008-11-189944  
11. Sahin F, Akay OM, Ayer M, et al. Pesg PNH diagnosis, follow-up and treatment guidelines. Am J Blood Res. 2016;6(2):19-27.  
12. Cella D, Lai JS, Chang CH, Peterman A, Slavin M. Fatigue in cancer patients compared with fatigue in the general United States population. Cancer. 2002;94(2):528-538. doi:10.1002/cncr.1024  
13. Montan I, Lowe B, Cella D, Mehnert A, Hinz A. General population norms for the Functional Assessment of Chronic Illness Therapy (FACIT)-fatigue scale. Value Health. 2018;21:1313-1321. doi:10.1016/j.jval.2018.03.013