CLINICAL
NEWS JACC in a FLASH
Featured topics in the current and recent
issues of the JACC family of journals
Fewer Cardiovascular Drugs Being
Studied in Clinical Trials
The number of cardiovascular drugs
in the research pipeline has declined
across all phases of development in
the last 20 years even as cardiovascular disease has become the number
one cause of death world-wide, according to research published Aug. 29
in JACC: Basic to Translational Science.
While the development and use of
new prescription drugs have been associated with a significant reduction
in cardiovascular mortality over the
past 2 decades, cardiovascular disease
is still the leading cause of death in
the developing world and accounts
for one in three deaths in the United
States. There has been growing con-
“These findings
are not entirely
glass halfempty.”
—Douglas L. Mann, MD
12
CardioSource WorldNews
cern over the decline in the development of new therapies.
Researchers analyzed data from a
large commercial database of drug development activity, which tracks the
pipeline of pharmaceutical research
and development projects. The study
included all products that had entered
Phase 1 clinical trials between Jan. 1,
1990, and Dec. 31, 2012, and that
focused on drugs intended to treat
cardiovascular disorders.
During the trial period, 347 cardiovascular drugs entered Phase 1 testing,
with the most common types being
antihypertensive agents, lipid-lowering
agents, and anticoagulants. The number
of cardiovascular drugs entering clinical trials in all stages of development
declined over time. Between 1990 and
1995, 108 of 679 (16%) of Phase 1
t rials were initiated for cardiovascular
drugs, compared to 125 of 2,366 (5%)
of Phase 1 trials between 2005 and
2012. Cardiovascular drugs accounted
for 21% of Phase 3 trials in 1990 but
only 7% in 2012. By comparison, the
number of cancer drugs increased over
the same time period.
“These findings shed light on several important shifts in cardiovascular
research and development activity
over the past 2 decades. Importantly,
while the overall number of new
investigational cardiovascular drugs
has declined, we also found a relative
growth in the number of drugs target-
ing novel biological pathways,” said
Aaron S. Kesselheim, MD, JD, MPH,
senior author of the study.
Half of cardiovascular drugs entering Phase 3 trials targeted a novel biological pathway, or one for which the
U.S. Food and Drug Administration
(FDA) had not yet approved a therapeutic agent. The rate of novel drugs
entering Phase 3 increased from 27%
in 1990-1991 to 57% in 2012. The
development of most cardiovascular
drugs was sponsored by large pharmaceutical companies, but the number
sponsored by small and medium-sized
companies grew over time.
“These findings are not entirely
glass half-empty,” said Douglas L.
Mann, MD, editor-in-chief of JACC:
Basic to Translational Science. “Part of
the decline in new drugs is that there
are less ‘me too’ drugs that are similar
to those already available. The study
also refutes the premise that cardiovascular drugs are often riskier to develop
than drugs in other clinical categories.”
In an accompanying editorial comment, Mona Fiuzat, PharmD; Norman Stockbridge, MD; and Robert
M. Califf, MD, emphasized the need
for more translational basic research to
identify new drug targets and the need
to develop better strategies to identify
successful drug candidates in Phase 2.
“Because drug development follows science, continued investment
in the basic biology of cardiovascular
disease is needed, and because large
populations are impacted, attention
to improved efficiency of the evidence
generation system will be needed
to generate needed sample sizes for
definitive trials at a lower cost,” they
said. “Finally, involving the full community including industry, the National Institutes of Health, academic
experts, funding agencies, regulators,
practitioners, and patients will be an
important step in strengthening the
science and advancing the field.”
Hwang T, Lauffenburger J, Franklin J,
Kesselheim A. JACC: Basic to Translational
Science. 2016;1(5):301-8.
Longer-Term
DAPT May Benefit
Complex PCI
Patients
Alongside other established clinical
risk factors, procedural complexity
is an important parameter to take
into account when tailoring upfront
duration of dual antiplatelet therapy
(DAPT) following complex percutaneous coronary intervention (PCI)
with drug-eluting stents, according
to a study presented Aug. 29 during
the ESC Congress 2016 in Rome and
simultaneously published in JACC.
“[P]atients who
undergo complex
PCI might
benefit from
upfront longer
DAPT duration
to prevent MACE,
irrespective
of clinical
presentation.”
September 2016