|
E-mail this page to a friend!
Diabetes Medication Awaiting FDA Approval May
Increase Deaths, Cardiovascular Risk
FDA encouraged to delay muraglitazar for additional
safety studies
Oct. 20, 2005 - A new medication under review by
the Food and Drug Administration that may regulate blood glucose levels
and have a beneficial effect on blood cholesterol and lipid levels for
patients with Type 2 diabetes appears to increase the risk for major
adverse cardiovascular events and death, according to a new study in
JAMA. The study and an accompanying editorial were released early
online today at
www.JAMA.com because of their timeliness and potential importance
for public health.
| |
Update on Story |
|
| |
Bristol-Myers Squibb Statement on Muraglitazar
Oct. 27, 2005
- On October 18, the U.S. Food and Drug Administration (FDA)
issued an approvable letter for muraglitazar, Bristol-Myers
Squibb Company's investigational oral medicine for the treatment
of type 2 diabetes. The FDA requested additional information
from ongoing clinical trials to more fully address the
cardiovascular safety profile of muraglitazar. We and our
partner, Merck & Co., Inc., have determined that to receive
regulatory approval and to achieve commercial success,
additional studies may be required because the ongoing trials
were not designed to answer questions raised by the FDA. The
additional studies could take approximately five years to
complete.
In addition,
Bristol-Myers Squibb has agreed to begin discussions with Merck
to terminate the collaborative agreement. Bristol-Myers Squibb
will continue discussions with the FDA and will consider a range
of options including conducting additional studies or
terminating further development of muraglitazar. |
|
| |
Related Stories |
|
| |
Campaign Begins Empowering Older Adults to Manage
Their Diabetes
Revitalized campaign shows older adults that the power to control is in
their hands.
Oct. 20 – A new campaign kicked off today the newly
updated “The Power to Control Diabetes Is in Your Hands” awareness
campaign for older adults with diabetes. The goal of the campaign is to
help the 18.3 percent of adults age 60 and older senior citizens with
diabetes manage their disease. The highlights include a community action
kit and a brochure designed to reach older adults with diabetes and
their loved ones. Read
more...
More on Senior Health and Medicine -
click |
|
The medication, muraglitazar, is in a class of
drugs called dual peroxisome proliferator-activated receptors (PPARs),
that affect lipid levels and glycemic control in diabetic patients. The
studies on muraglitazar were reviewed by an FDA advisory committee on
September 9, 2005, resulting in a vote of 8 to 1 recommending approval
for its use as a monotherapy in controlling blood glucose levels in
patients with type 2 diabetes.
On October 18, 2005, the FDA issued an “approvable
letter” for muraglitazar, indicating that the drug could be approved
once the FDA receives and reviews additional information.
Steven E. Nissen, M.D., and colleagues from the
Cleveland Clinic Foundation, reviewed the FDA briefing documents
available via the FDA website for the September 9 public hearing. The
researchers analyzed the muraglitazar trials performed in diabetic
patients, publicly released by the sponsor and FDA for the advisory
panel meeting.
The documents provided data for five clinical
trials that assessed safety and efficacy in diabetic patients. The
researchers restricted their analysis to treatment groups using
muraglitazar doses of 5 mg/d or less. The analysis yielded 2,374
patients exposed to muraglitazar and 1,351 patients exposed to other
agents, of which 823 received pioglitazone (a currently available PPAR)
and 529 placebo.
The patients were relatively young (average age 55
years or less) and obese (average body mass index greater than 30). The
studies included both men and women participants and the diabetes
control among the participants was relatively poor.
“In the muraglitazar-treated patients, death, MI
(heart attack), or stroke occurred in 35 of 2,374 (1.47 percent)
patients compared with 9 of 1,351 (0.67 percent) patients in the
combined placebo and pioglitazone treatment groups (controls),” the
authors found.
“The results of this analysis are concerning,” the
authors write. “For the most widely accepted composite end point of
death, MI (heart attack), and stroke the RR (relative risk) for
muraglitazar was 2.23. Other end points using narrower definitions
(including only cardiovascular death) or broader composites (including
CHF [congestive heart failure] and TIA [transient ischemic attack]
events) showed similar risks.”
The researchers note that the results are
particularly concerning because the excess of adverse events was
observed after the study participants had limited drug exposure ranging
from 24 to 104 weeks.
The researchers state that “atherosclerotic
cardiovascular disease is particularly common in patients with type 2
diabetes, representing the cause of death in approximately 80 percent of
diabetic patients. Thus, any drug used to treat diabetes requires
careful scrutiny for its effects on atherosclerosis-related outcomes,
such as MI and stroke.” The researchers also note there are some
limitations to their analysis as they did not have access to original
trial databases.
“Nonetheless, some important conclusions are
warranted. Muraglitazar appears to increase the risk for morbidity and
mortality in diabetic patients during relatively short-term treatment.
The estimated magnitude of this risk is substantial with RRs indicating
a doubling for irrevocable, major end points and composite outcomes. The
consistency of these RRs suggests that this result is not due to
chance. Accordingly, muraglitazar should not be used or approved to
treat patients with diabetes until an appropriate dedicated trial to
assess cardiovascular outcomes is performed,” the authors conclude.
Editorial: Selling Safety – Lessons from
Muraglitazar
In an accompanying editorial, James M. Brophy,
M.D., F.R.C.P., Ph.D., from McGill University, Montreal, Canada, writes,
“muraglitazar is the first dual PPAR agonist to be considered for
general marketing both as mono and combined therapy by the U.S. Food and
Drug Administration. Given the emerging epidemic of diabetes, it is
easy to understand the enthusiasm for this new class of drugs.”
“Last month, a FDA advisory committee reviewed
muraglitazar’s efficacy and safety data and recommended approval.
However, in this issue of JAMA, Nissen and colleagues have re-analyzed
this data and challenge the advisory board’s recommendation.”
In addition to underscoring the cardiovascular
risks evident in the analysis by Nissen et al, Dr. Brophy notes that
carcinogenicity (cancer) also has been a concern in animal studies
involving other PPAR agonists. “While the manufacturer’s presentation to
the advisory committee concluded that cancer rates were not increased,
there were 34 cancers reported in the muraglitazar group and one in the
control group.” He goes on to question some of the methodological
decisions in the sponsor’s FDA application that “may foster an illusion
of safety” including the selection of the study population that is not
representative of potential future users; underpowered studies
increasing the failure rate to detect meaningful safety differences; and
concentrating on reductions in surrogate laboratory values rather than
in meaningful patient health outcomes.
“In conclusion, while muraglitazar may yet prove to
be a valuable addition to our clinical armamentarium, Nissen and
colleagues are to be congratulated for their meticulous examination of
the current evidence and for drawing our attention to its potential
cardiovascular risks. Residual safety concerns surrounding
carcinogenicity also have not been completely resolved. The question
now is which safety message will the FDA buy?”
(JAMA. 2005. Available at
www.JAMA.com).
Click to More Senior News on the
Front Page
Copyright: SeniorJournal.com |
