sHTG Results | Efficacy

CORE and CORE2 efficacy results

TRYNGOLZA achieved statistically significant, robust triglyceride reductions at 6 months in adults with severe hypertriglyceridemia (sHTG)1

Primary endpoint1
Down arrow next to 72%.

statistically significant mean change in fasting triglycerides with TRYNGOLZA 80 mg compared with placebo at Month 6* (P<0.0001) in addition to background lipid-lowering therapy

CORE1
TRYNGOLZA 50 mgTRYNGOLZA 80 mg
1169
Mean baseline (mg/dL)		1169
Mean baseline (mg/dL)
−63%−72%
placebo-corrected difference from baseline to Month 6*†placebo-corrected difference from baseline to Month 6*†
CORE21
TRYNGOLZA 50 mgTRYNGOLZA 80 mg
968
Mean baseline (mg/dL)		1088
Mean baseline (mg/dL)
−49%−55%
placebo-corrected difference from baseline to Month 6*†placebo-corrected difference from baseline to Month 6*†

*Average of Weeks 25 and 27.1
†Reached statistical significance (P<0.0001).1

SELECT IMPORTANT SAFETY INFORMATION

Adverse Reactions for sHTG


Most common adverse reactions in patients with sHTG (incidence ≥2% higher than placebo) were injection site reactions and liver enzyme increases.

The rapid reduction and consistent triglyceride control your patients need with TRYNGOLZA1

TRYNGOLZA demonstrated statistically significant decreases in fasting triglycerides at Month 6 and Month 12.1

Mean percent change in fasting triglycerides over time1
A graph of the CORE study results showing participants change from baseline at month 6.
TRYNGOLZA Autoinjector

Monthly dosing with TRYNGOLZA provided consistent triglyceride lowering throughout the 12-month treatment period.1

Next sHTG lipid parameters

Beyond triglycerides: multiple atherogenic lipid markers

Atherogenic burden reduction (Total ApoB, non–HDL-C) with mechanism-driven lipid remodeling.1-5

 

  • Accelerated TRL clearance with apoC-III inhibition resulted in a favorable shift in overall lipid profile with increases in LDL-C1-5
Placebo-corrected difference from baseline at Month 61
A graph of the CORE study results showing TRYNGOLZA and multiple lipid and biomarker parameters, such as remnant cholesterol, non-HDL-C, and others.

Mean percentage change in HDL-C compared with placebo at 6 months2:

  • 64% with TRYNGOLZA 50 mg
  • 85% with TRYNGOLZA 80 mg

LIMITATION: Data shown were exploratory analyses; observed results should be interpreted with caution.

*Reached statistical significance (P<0.05).1
Analysis results were based on an analysis-of-covariance model with treatment, 2 randomization stratification factors (qualification fasting triglycerides ≥880 mg/dL [yes/no] and prior history of pancreatitis within 10 years prior to screening [yes/no]) as the fixed effects, and baseline value as a covariate; missing data were imputed using a placebo-washout multiple-imputation approach.1
apo=apolipoprotein; HDL-C=high-density lipoprotein cholesterol; LDL-C=low-density lipoprotein cholesterol; TRL=triglyceride-rich lipoprotein.

Next sHTG responder analyses

Observed triglyceride levels <880 mg/dL, <500 mg/dL, and <150 mg/dL at 12 months1

>85% of patients reached triglyceride levels <500 mg/dL with TRYNGOLZA.1

Pooled responder analyses at 1 year1
A graph of pooled responder analyses at 1 year.

*Achievement of triglyceride levels <880 mg/dL, <500 mg/dL, and <150 mg/dL at 12 months among patients with baseline levels above these thresholds.1

†LIMITATION: Data shown were exploratory analyses; observed results should be interpreted with caution.

Next sHTG AP reduction

TRYNGOLZA is the first therapy indicated to reduce the risk of acute pancreatitis (AP) events in adults with severe hypertriglyceridemia1

Secondary endpoint1
Down arrow next to 91%.

reduction in the adjudicated acute pancreatitis event rate with TRYNGOLZA 50 mg compared with placebo in addition to background lipid-lowering therapy1

AP EVENT RATE REDUCTION BY
DOSE COMPARED WITH PLACEBO1
TRYNGOLZA 50 mg
RR: 0.09 (95% CI: 0.02, 0.42)		-91%
TRYNGOLZA 80 mg
RR: 0.24 (95% CI: 0.08, 0.69)		-76%

Pancreatitis events were assessed as a secondary endpoint in an integrated analysis of CORE and CORE2. Events were adjudicated by a blinded, independent committee according to the Revised Atlanta Diagnostic Criteria.1
RR=rate ratio.

SELECT IMPORTANT SAFETY INFORMATION

Adverse Reactions for sHTG


Most common adverse reactions in patients with sHTG (incidence ≥2% higher than placebo) were injection site reactions and liver enzyme increases.

Kaplan-Meier estimate of time to first AP event in patients with sHTG (pooled analysis of CORE and CORE2) (N=1061)1
A graph showing estimate of time to first AP event in patients with sHTG.

 

 

85% reduction in AP events (RR: 0.15; 95% Cl: 0.05, 0.40) in the pooled TRYNGOLZA group1

  • 17 patients (4.8%) in the pooled placebo group experienced 22 events of adjudicated AP1
  • 5 patients (0.7%) in the combined pooled TRYNGOLZA group experienced 7 events1

Pancreatitis events were assessed as a secondary endpoint in an integrated analysis of CORE and CORE2. Events were adjudicated by a blinded, independent committee according to the Revised Atlanta Diagnostic Criteria. Event rates over 53 weeks were compared between pooled TRYNGOLZA (50 mg and 80 mg) and pooled placebo using a negative binomial regression model.1
The time was censored at Week 53 or at the posttreatment follow-up termination date, whichever occurred first. The time to the first adjudicated pancreatitis event was compared between the pooled TRYNGOLZA treatment group and the placebo group using a log-rank test, stratified by study identifier (CORE or CORE2).1

Low numbers needed to treat (NNT) were observed in patients most at risk of AP2,3

The NNT communicates how many patients on average would need to be on a given treatment for a defined period to benefit compared with not using the therapy. The lower the NNT, the more effective the treatment.4,5

NNT with TRYNGOLZA over 1 year to prevent 1 AP event2,6


TGs ≥500 mg/dL
NNT=20*


TGs ≥880 mg/dL
NNT=9*

TGs ≥880 mg/dL 
+ prior AP history
NNT=4*

* LIMITATION: Data shown were exploratory analyses; observed results should be interpreted with caution.

 

TG=triglyceride.

Next See the sHTG safety profile
  • Seventeen participants (4.8%) in the pooled placebo group experienced 22 total events of adjudicated acute pancreatitis, compared with 5 patients (0.7%) in the combined pooled TRYNGOLZA group who experienced 7 total events1
  • Mean pancreatitis event rate ratio of 0.15 (95% CI: 0.05, 0.40) vs placebo (P=0.0002)1

Pancreatitis events were assessed as a secondary endpoint in a combined analysis of CORE and CORE2. Events were adjudicated by a blinded, independent committee according to the Revised Atlanta Diagnostic Criteria. Event rates were compared between pooled TRYNGOLZA (50 mg and 80 mg) and pooled placebo using a negative binomial regression model.1

What is number needed to treat (NNT)?

NNT is an important measure of efficacy

  • The NNT communicates how many patients on average would need to be on a given treatment for a defined period to benefit compared with not using the therapy4,5
  • The lower the NNT, the more effective the treatment5
NNT ratings7,8
NNT ≤6Represents exceptional clinical benefit
NNT <20Indicates strong clinical benefit
NNT 20–50Considered acceptable therapeutic benefit depending on the severity of the condition being prevented
NNT >50Generally represents marginal therapeutic benefit requiring careful consideration of treatment burden