Studied head-to-head vs
agalsidase beta1,2
The efficacy and safety of Elfabrio, 1 mg/kg every 2 weeks, vs agalsidase beta were studied in BALANCE, a head-to-head, randomized, double-blind, 2-year, active-controlled trial.1,2
- Prior agalsidase beta: >1 year, average of 5.7 years
- Primary study: 24 months (n=78, ITT=77, PP=72)
- Open-label extension: Up to 60 months
Primary endpoint
- Annualized rate of change in eGFR (eGFR slope) assessed over 2 years
Safety endpoints
- Treatment-emergent adverse events (TEAEs), infusion-related reactions (IRRs), anti-drug antibodies (ADAs)
BALANCE (Trial 2 in the Elfabrio Prescribing Information) provided confirmatory evidence in the FDA’s approval of Elfabrio. The data discussed are not intended to establish noninferiority or superiority to any other marketed drug product on the basis of safety or efficacy.3*
| * | Source: Elfabrio approval package. https://www.accessdata.fda.gov |
| eGFR, estimated glomerular filtration rate; FDA, Food and Drug Administration; ITT, intention to treat; PP, per protocol. | |
Comparable effect on eGFR vs agalsidase beta over 2 years1,3
Evaluation of change in mean eGFR values over 24 months1,3
eGFR mean slope, mL/min/1.73 m2/year1
|
Elfabrio
n=52 |
agalsidase beta
n=25 |
Difference
(95% CI) |
|---|---|---|
| -2.4 | -2.3 | -0.1 (-2.3, -2.1) |
The comparable effect on eGFR aligns with the FDA’s determination that the slopes in each arm were comparable based on a series of supportive statistical analyses.
The FDA has indicated that the magnitude of drug effect of agalsidase beta in a study population similar to that of BALANCE cannot be sufficiently quantified and as such, a noninferiority margin cannot be determined for BALANCE.
CI, confidence interval.
Picture this: Low immune response after switching to Elfabrio3
 ADA incidences3†‡ |
Elfabrio
n=52 |
|---|---|
| Positive IgG ADA at one or more time points post-treatment | 20 (38.5%) |
| Treatment-emergent ADA | 6 (11.5%) |
| Titer-boosted response | 3 (50%) |
| Induced response | 3 (50%) (2 transient + 1 persistent) |
| Positive for ADA at baseline | 18 (34.6%) |
| Negative for ADA at baseline | 34 (65.4%) |
| Positive at baseline and positive in at least one post-baseline visit | 17 (94.4%) |
| Positive at baseline and remained negative in all post-baseline visits | 1 (5.6%) |
| Negative at baseline and became positive in at least one post-baseline visit | 3 (8.8%) |
| Negative at baseline and remained negative in all post-baseline visits | 31 (91.2%) |
- Clinical significance of total ADAs and their effect on treatment is not completely understood
- Testing for ADAs before treatment with Elfabrio and continuing to monitor routinely throughout treatment can give you the full picture
| † | The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. |
| ‡ | Source: Elfabrio approval package. https://www.accessdata.fda.gov |
IgG, immunoglobulin G.
Demonstrated safety profile for Elfabrio1
BALANCE (Trial 2):
Safety was evaluated in a head-to-head trial assessing patients switching to Elfabrio after >1 year prior use of agalsidase beta (average of 5.7 years):
| Adverse reactions in adults with Fabry disease§ |
Elfabrio
n=52 n (%) |
agalsidase beta
n=25 n (%) |
|---|---|---|
| Infusion-associated reaction||¶ | 17 (32) | 8 (32) |
| Nasopharyngitis | 11 (21) | 4 (16) |
| Headache | 11 (21) | 5 (20) |
| Diarrhea | 10 (19) | 6 (24) |
| Fatigue | 9 (17) | 4 (16) |
| Nausea | 9 (17) | 3 (12) |
| Back pain | 8 (15) | 5 (20) |
| Pain in extremity | 8 (15) | 4 (16) |
| Sinusitis | 8 (15) | 3 (12) |
| Abdominal pain | 6 (12) | 0 (0) |
| Proteinuria | 6 (12) | 0 (0) |
| Hypersensitivity¶# | 5 (9) | 4 (16) |
| Upper respiratory tract congestion | 4 (8) | 0 (0) |
| Neuralgia | 4 (8) | 0 (0) |
| Peripheral neuropathy | 3 (6) | 0 (0) |
| Sciatica | 3 (6) | 0 (0) |
| Infusion site extravasation | 3 (6) | 0 (0) |
| Hematuria | 3 (6) | 0 (0) |
| Source: Elfabrio Prescribing Information; 2023. | ||
| § | Adverse reactions were those that occurred in ≥5% of Elfabrio-treated patients. |
| || | ”Infusion-associated reaction” (IAR) includes nausea, vomiting, abdominal pain, diarrhea, fatigue, chills, malaise, non-cardiac chest pain, hypersensitivity, body temperature increased, burning sensation, neuralgia, agitation, throat irritation, pruritic rash, and flushing. Events occurring within 24 hours. |
| ¶ | The events of hypersensitivity and pruritic rash fall in both hypersensitivity and IAR categories. |
| # | ”Hypersensitivity” includes macular rash, pruritic rash, and face swelling. Events occurring within 24 hours. |
Low rates of TEAEs and IRRs3
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|
Elfabrio
|
agalsidase beta
|
|||
|---|---|---|---|---|
| ADA negative N=34 |
ADA positive N=18 |
ADA negative N=17 |
ADA positive N=8 |
|
| Number of related TEAEs (rate**)3 |
13 (20.08) | 29 (87.18) | 28 (83.64) | 48 (295.80) |
| Total # of IRRs (rate††)3 |
5 (0.3) | 8 (0.9) | 19 (2.2) | 32 (7.5) |
| ** | A TEAE was defined as related if it was reported as possibly, probably, or definitely related to the study drug. Rate is calculated as the adjusted number of events per 100 years of exposure.3 |
| †† | IRRs are not injection site reactions. TEAEs occurred during the infusion or within 2 hours after the completion of the infusion, and causality was assessed as definitely, probably, or possibly related. Rate is presented as the number of IRRs per 100 infusions.3 |
| ‡‡ | The data discussed are not intended to establish noninferiority or superiority to any other marketed drug product on the basis of safety or efficacy. |
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