TABLE
Phase III and Long-Term Extension Trial Results for Studies of PCSK9s
N
Baseline LDL-C Entry
Criteria, Median (mg/dl)
MENDEL-2
614
100–190, 143
ODYSSEY MONO
103
100–190, 140
2,067
≥150, 109
ODYSSEY COMBO II
720
ODYSSEY COMBO I
YUKAWA-2
Trial Name
Drug and
Dosing (mg)
LDL-C Reduction vs. Placebo
Evo 140 Q2W
57% and 39%* at 10-12 weeks†
Evo 420 Q4W
57% and 40%* at 10-12 weeks†
Ali 75 Q2W‡
32%• at week 24
Evo 140 Q2W
66-75% and 44-46%* at weeks 10-12†
Evo 420 Q4W
63-75% and 39-55%* at weeks 10–12†
≥70, 108
Ali 75 Q2W‡
30%* at week 12
316
≥70, 97
Ali 75 Q2W‡
46% at week 24
404
≥100, N/A
Evo 140 Q2W
74-75% at weeks 10-12†; 75-76% at week 12
Evo 420 Q4W
66-81% at weeks 10-12†; 61-76% at week 12
Evo 420 Q4W
49-62% at week 52
Monotherapy
In combination with statin
LAPLACE-2
In addition to diet alone, statin, or statin + ezetimibe
DESCARTES
901
≥75, 104
ODYSSEY CHOICE I
803
>Goal, 122
GAUSS-2
307
>Goal, 193
ODYSSEY ALTERNATIVE
314
>Goal, 191
ODYSSEY CHOICE II
233
>Goal, 158
Ali 75 Q2W
Ali 300 Q4W
52-59% at week 24
Evo 140 Q2W
38%* at week 12; 38%* at weeks 10-12†
Evo 420 Q4W
38%* at week 12; 39%* at week 10-12†
Ali 75 Q2W‡
30%* at week 24
Ali 75 Q2W‡
56% at week 24
Ali 150 Q4W§
56% at week 24
Evo 140 Q2W
59% at 12 weeks; 60% at weeks 10-12†
Evo 420 Q4W
61% at 12 weeks; 66% at weeks 10-12†
Statin intolerance
Heterozygous familial hypercholesterolemia
RUTHERFORD-2
331
≥100, 154
ODYSSEY FH I and II
735
≥160, 141
Ali 75 Q2W‡
51-58% at week 24
≥130, 347
Evo 420 Q4W
31% at week 12
Homozygous familial hypercholesterolemia
TESLA Part B
50
Long-term extension studies
OSLER-1 and OSLER-2
1,359
≥100, 120
Evo 420 Q4W
52% at week 52 (vs. standard of care)
ODYSSEY LONG TERM
2,341
≥70, 122
Ali 150 Q2W
62% at week 24
The safety and tolerability profile of the two
most extensively studied MoAbs (alirocumab,
evolocumab) for periods of up to 2 years appears
promising; however, longer exposure is necessary
to more completely evaluate potentially delayed
adverse effects, such as neurocognitive impairment
or cancer. Given the reduction in LDL-C observed in
phase II and III trials to date and the analyses of CV
events in longer-term studies, major vascular events
could be reduced by 40% to
50% in high-risk patients if
the benefits follow a similar
relationship as that observed
with statins.
Overall, the authors of the
JACC review caution against
excessive exuberance pending
To listen to an
interview with Robert
the results of the ongoing CV
P. Guigliano, MD, on
outcome trials. Furthermore,
the latest in PCSK9
given increasing constraints
inhibitors, scan the
code. The interview
on health care spending and
was conducted by
the higher bars being set by
Patrick T. O’Gara, MD.
the Centers for Medicare and
Medicaid Services for coverage
determination of novel therapies, Giugliano and Sabatine
anticipated the availability of
MoAbs to PCSK9 will be limited initially to those patients
who are at high cardiovascular
risk, who have an LDL-C that is not well controlled
despite intensive therapy with a statin + ezetimibe,
or who cannot tolerate statin therapy. ■
(Editor’s Note: ACCEL has featured several interviews discussing these drugs, includ