Important Safety Information: Contraindications: CERDELGA is contraindicated in the following patients based on CYP2D6 metabolizer status due to the risk of cardiac arrhythmias from prolongation of the PR, QTc, and/or QRS cardiac intervals: Extensive Metabolizers (EMs) taking a strong or moderate CYP2D6 inhibitor concomitantly with a strong or... View more

Switch Patient Study (ENCORE)

Cerdelga is the ONLY first-line oral therapy for most adults with Gaucher disease type 1, indicated for the long-term treatment of both naive and switch patients.1,2

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Disease Stability Maintained in Patients Switched from ERT to Cerdelga

The efficacy and safety of Cerdelga in patients previously treated with enzyme replacement therapy (ERT) was studied in a phase 3 ENCORE trial. ENCORE included a primary and open-label extension phase of Cerdelga in which patients were evaluated at 12 months and 2 years, and were observed for up to 4 years. Explore the results below.1,5,8

Key study design parameters (primary and open-label extension phases)1,5,6,8

  • ENCORE was a randomized, open-label, active-controlled, non-inferiority, multicenter clinical study.
  • 159 patients previously treated with ERT were randomized 2:1 to receive Cerdelga or imiglucerase for the duration of the 12-month primary analysis period.
  • All patients who completed the 12-month primary analysis period were allowed to participate in the open-label extension phase and receive Cerdelga.
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Chart showing phase 3 switch key study design parameters
View the full study design for complete details, including inclusion criteria and endpoints.

ENCORE Primary
Analysis Data

Switch with confidence. Switch to Cerdelga.

Cerdelga is the ONLY first-line oral treatment for most adults with Gaucher disease type 1 that maintained long-term disease stability in patients who were switched from ERT.1,2

PRIMARY ANALYSIS

After 1 year of treatment, ENCORE study results showed noninferiority to imiglucerase; 85% of Cerdelga patients met the primary composite endpoint compared to 94% in the imiglucerase group. The lower bound of the 95% CI (-17.6%) was within the prespecified noninferiority margin of -25%.1,5

There were no clinically meaningful differences between patients receiving Cerdelga vs imiglucerase (ERT), for any of the 4 parameters of the composite endpoint.1,5

Disease stability maintained in patients switched from ERT to Cerdelga1,5

Chart showing disease stability maintained in patients switched from ERT to Cerdelga

Of the patients who did not meet stability criteria for the individual components, 12 of 15 Cerdelga patients and 3 of 3 imiglucerase patients remained within therapeutic goals for Gaucher disease type 1.1
Per-protocol population. Note: Error bars represent exact 95% CIs around the proportion.
*Spleen percentages are based on the total number of nonsplenectomized patients in each treatment group.
Adapted from Cox et al. Lancet. 2015.

Maintained stability in spleen and liver volume for up to 12 months1,5,6

Chart showing stability in spleen for up to 12 months

Chart showing stability in liver for up to 12 months

Maintained stability in hemoglobin level and platelet count for up to 12 months1,5,6

Chart showing stability in hemoglobin level for up to 12 months

Chart showing stability in hemoglobin level for up to 12 months

Baseline is defined as before the first dose of study medication in the primary analysis phase. MN=multiples of normal.

All patients who completed the 12-month primary analysis period were allowed to participate in the open-label extension (OLE) phase and receive Cerdelga. Of the 159 patients in the primary analysis phase, 152 entered the extension phase (101/102 patients in the Cerdelga arm and 51/52 patients in the imiglucerase arm continued in the OLE phase and switched to Cerdelga).6,8 See the results from the OLE phase below.

ENCORE Long-Term, Open-Label Extension Data

Maintained stability in visceral and hematologic disease parameters for up to 2 years in the ENCORE study.1

  • In the open-label extension phase of ENCORE, 141 of 146 patients (42 patients previously treated with enzyme treatment therapy and 99 who continued treatment with Cerdelga) were evaluated for stability, as defined in the initial 12 months of the trial, in clinical parameters (composite of spleen and liver volume, hemoglobin level, and platelet count).
  • Stability was shown in 120/141 (85%) patients at one year and 111/129 (86%) patients at 2 years of Cerdelga exposure.

Mean changes from baseline in individual components of the primary endpoint composite score8

Chart showing ENCORE long-term, open-label extension data for the spleen

Chart showing ENCORE long-term, open-label extension data for the liver

Chart showing ENCORE long-term, open-label extension data for hemoglobin level

Chart showing ENCORE long-term, open-label extension data for hemoglobin level

Patients were followed for up to 4 years of Cerdelga treatment. Due to decreasing sample size, results after the 2-year analysis require cautious interpretation.

Percentage changes from baseline were calculated by dividing the LS mean change from baseline for each year (as reported in Cox et al, Blood, 2017) by the baseline value and multiplying by 100.

Baseline was defined as the last available assessment before Cerdelga treatment initiation (day 1 for patients originally randomized to Cerdelga and week 52 + 1 day for patients originally randomized to imiglucerase).

LS=least-square; CI=confidence interval; MN=multiples of normal.

Patients can be switched to Cerdelga in as little as 24 hours after their last ERT infusion.1

ENCORE Safety

Adverse reactions occurring in ≥5% of GD1 patients switching from ERT to Cerdelga and more frequently than imiglucerase in the primary analysis period1,5*
  • 2 (2%) patients given Cerdelga discontinued the study due to AEs in the primary analysis period.5
  • No new safety signals were observed in the open-label extension period.8

Primary Analysis Period

ADVERSE REACTION,
n (%)
CERDELGA® (n=106)   IMIGLUCERASE (n=53)
Fatigue 15 (14)   1 (2)
Headache 14 (13)   1 (2)
Nausea 13 (12)   0 (0)
Diarrhea 13 (12)   2 (4)
Back Pain 13 (12)   3 (6)
Pain in
Extremity
12 (11)   1 (2)
Upper
Abdominal
Pain
11 (10)   0 (0)
Dizziness 8 (9)   0 (0)
Asthenia 8 (9)   0 (0)
Cough 7 (7)   0 (0)
Dyspepsia 7 (7)   2 (1)
Gastro
esophageal
Reflux
Disease
7 (7)   0 (0)
Constipation 5 (5)   0 (0)
Palpitations 5 (5)   0 (0)
Rash 5 (5)   0 (0)

*ENCORE was not designed to support comparative claims for Cerdelga for the adverse reactions reported in this table.

References:
  1. Cerdelga [prescribing information]. Cambridge, MA: Sanofi Genzyme. 2018.
  2. Pleat R, Cox TM, Burrow TA, et al. Stability is maintained in adults with Gaucher disease type 1 switched from velaglucerase alfa to eliglustat or imiglucerase: A sub-analysis of the eliglustat ENCORE trial. Mol Genet Metab Rep. 2016;9:25-28.
  3. Mistry PK, Lukina E, Ben Turkia H, et al. Outcomes after 18 months of eliglustat therapy in treatment-naïve adults with Gaucher disease type 1: the phase 3 ENGAGE trial. Am J Hematol. 2017;92(11):1170–1176
  4. Mistry PK, Lukina E, Ben Turkia H, et al. Effect of oral eliglustat on splenomegaly in patients with Gaucher disease type 1. The ENGAGE randomized clinical trial. JAMA. 2015;313(7):695-706.
  5. Cox TM, Drelichman G, Cravo R, et al. Eliglustat compared with imiglucerase in patients with Gaucher’s disease type 1 stabilised on enzyme replacement therapy: a phase 3, randomized, open-label, non-inferiority trial. Lancet. 2015;385(9985):2355-2362.
  6. Data on file. Sanofi Genzyme
  7. Peterschmitt MJ, Cox GF, Ibrahim J, et al. A pooled analysis of adverse events in 393 adults with Gaucher disease type 1 from four clinical trials of oral eliglustat: Evaluation of frequency, timing, and duration. Blood Cells Mol Dis. 2018;68:185-191.
  8. Cox TM, Drelichman G, Cravo R, et al. Eliglustat maintains long-term clinical stability in patients with Gaucher disease type 1 stabilized on enzyme therapy. Blood. 2017;129(17):2375-2383.