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

Naive Patient Studies (ENGAGE and Phase 2)

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

View Indications and Usage

Proven Efficacy and Safety in Naive Patients

The efficacy and safety of Cerdelga was studied in a Phase 3 ENGAGE trial of treatment-naive patients. ENGAGE included a primary and open-label extension phase of Cerdelga in which patients were evaluated at 9 months and 2 years, and were observed for up to 4.5 years. Explore the results below.1,4,6

Key study design parameters (primary and open-label extension phases)1,3,4,6

  • ENGAGE was a randomized, double-blind, placebo-controlled, multicenter clinical study
  • 40 treatment-naive patients were randomized in a 1:1 ratio to receive Cerdelga or placebo for the duration of the 9-month blinded primary analysis period
  • On completing the 9-month primary analysis period, all patients had the opportunity to continue in the open-label ENGAGE trial extension, in which all patients received Cerdelga
Chart showing the phase 3 naive key study design parameters
View the full study design for complete details
View the full study design for complete details, including inclusion criteria and endpoints.

ENGAGE Primary Analysis Data

Start with Confidence. Start with Cerdelga.

Cerdelga is the ONLY first-line oral treatment for most adults with Gaucher disease type 1 that significantly improved visceral and hematologic parameters.1,2

Primary analysis data

Reduction in spleen and liver volume from baseline1,4

Chart showing the reduction in spleen volume from baseline

Difference between treatment groups was 30% (<0.0001). At baseline, mean spleen volumes were 12.5 and 13.9 MN in the placebo and Cerdelga groups, respectively.

Chart showing the reduction in liver volume from baseline

Difference between treatment groups was 6.6% (P=0.0072). At baseline, mean liver volumes were 1.4 MN for both groups.1,4

Improvement in hemoglobin level and platelet count from baseline1,4

Chart showing the improvement in hemoglobin level from baseline

Difference between treatment groups was 1.2 g/dL (P=0.0006). At baseline, mean hemoglobin levels were 12.8 and 12.1 g/dL in the placebo and Cerdelga groups, respectively.

Chart showing the improvement in platelet count from baseline

Difference between treatment groups was 41% (P<0.0001). At baseline, mean platelet counts were 78.5 and 75.1 x 109/L in the placebo and Cerdelga groups, respectively.

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

ENGAGE Long-Term, Open-Label Extension Data

Following the 9-month primary analysis period, all patients had the opportunity to continue to participate in the open-label extension (OLE) ENGAGE trial extension, in which all patients received Cerdelga.3

Of the 40 patients in the primary analysis phase, 39 entered the extension phase, including the 20 patients in the placebo arm of the primary analysis phase. See the results below.3

Long-term, open-label extension data

All 20 patients in the placebo arm of the primary analysis phase joined the Cerdelga arm of the open-label extension phase.3

Changes in spleen and liver volume from baseline for up to 2 years1,3,6

Chart showing changes in spleen volume from baseline for up to 2 years

At baseline, mean spleen volumes were 12.5 and 13.9 MN in the placebo and Cerdelga groups, respectively.

Chart showing changes in liver volume from baseline for up to 2 years

At baseline, mean liver volumes were 1.4 MN for both groups.

Changes in hemoglobin level and platelet count from baseline for up to 2 years1,3,6

Chart showing changes in hemoglobin level from baseline for up to 2 years

At baseline, mean hemoglobin levels were 12.8 and 12.1 g/dL in the placebo and Cerdelga groups, respectively.

Chart showing changes in platelet count from baseline for up to 2 years

At baseline, mean platelet counts were 78.5 and 75.1 x 109/L in the placebo and Cerdelga groups, respectively.

Patients were followed for up to 4.5 years of Cerdelga treatment. Due to decreasing sample size, results after the 2-year analysis require cautious interpretation.

Baseline is defined as before the first dose of study medication in the primary analysis phase. SEM=standard error of the mean; MN=multiples of normal; SD=standard deviation.

ENGAGE Safety

Adverse reactions occurring in ≥10% of treatment-naive Gaucher disease type 1 patients and more frequently than placebo1,4

  • No patients discontinued the ENGAGE study due to AEs in the primary analysis period.4
  • No new safety signals were observed in the open-label extension period.3

Primary Analysis Period

ADVERSE REACTION, n (%) CERDELGA® (n=20)   PLACEBO (n=20)
Arthralgia 9 (45)   2 (10)
Headache 8 (40)   6 (30)
Migraine 2 (10)   0 (0)
Flatulence 2 (10)   1 (5)
Nausea 2 (10)   1 (5)
Oropharyngeal Pain 2 (10)   1 (5)

Phase 2, Open-Label,
Naive Patient Study

Image of Phase 2, single-arm, naive patient study Image of Phase 2, single-arm, naive patient study
Continued improvements in visceral and hematologic parameters through 4 years1,9

In an uncontrolled study, improvements in spleen and liver volume, hemogloblin level, and platelet count continued through the 4-year treatment period. Patients were then observed up to 8 years.

Phase 2 Study: Also Analyzed Subgroups According to Baseline Disease Severity9.10

Due to small sample size, these analyses require cautious interpretation and clinical
significance of this data is unknown

Image of Phase 2, single-arm, naive patient study
References:
  1. Cerdelga [prescribing information]. Cambridge, MA: Sanofi Genzyme. 2021.
  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.
  9. Lukina E, Watman N, Dragosky M, et al. Outcomes after 8 years of eliglustat therapy for Gaucher disease type 1: final results from the phase 2 trial. AM J Hematol. 2019;94(1):29-38.
  10. Lau H, Lukina E, Watman N, et al. Long-term treatment response based on severity of Gaucher disease type 1 at baseline after 8 years of treatment with oral eliglustat: final efficacy and safety results from a phase 2 clinical trial in treatment-naïve adults. Oral presentation at: WORLDSymposium™; February 5-9, 2018; San Diego.