Here we go again

Here we go again

According to
a statement by the FDA, “FDA
is revising the prescribing information for Januvia (sitagliptin) and Janumet
(sitagliptin/metformin) to include information on reported cases of acute
pancreatitis in patients using these products.

the first in a new class of diabetic drugs called dipeptidyl peptidase-4
(DPP-4) inhibitors, is approved as an adjunct to diet and exercise to improve
glycemic control in adults with type 2 diabetes mellitus. 

post-marketing cases of acute pancreatitis, including two cases of hemorrhagic
or necrotizing pancreatitis in patients using sitagliptin, were reported to the
Agency between October 16, 2006 and February 9, 2009. Based on these reports,
FDA is working with the manufacturer of sitagliptin and sitagliptin/metformin
to revise the prescribing information to include:

·        Information
regarding post-marketing reports of acute pancreatitis, including the severe
forms, hemorrhagic or necrotizing pancreatitis.

·        Recommending
that healthcare professionals monitor patients carefully for the development of
pancreatitis after initiation or dose increases of sitagliptin or
sitagliptin/metformin, and to discontinue sitagliptin or sitagliptin/metformin
if pancreatitis is suspected while using these products.

·        Information
noting that sitagliptin has not been studied in patients with a history of
pancreatitis. Therefore, it is not known whether these patients are at an
increased risk for developing pancreatitis while using sitagliptin or
sitagliptin/metformin. Sitagliptin or sitagliptin/metformin should be used with
caution and with appropriate monitoring in patients with a history of

Merck (NYSE:MRK) the
makers of Januvia and Janumet issued the following response; “
Merck has thoroughly reviewed the safety
data for sitagliptin, and sitagliptin was not associated with an increase in
the incidence of pancreatitis in preclinical studies or in clinical trials of
up to two years in duration with more than 6,000 patients. Merck has also
carefully reviewed post marketing adverse experience reports, and Merck
believes these data do not demonstrate that a causal relationship exists
between sitagliptin and pancreatitis. Merck appreciates the important role that
the FDA plays in assessing the safety of medicines and, as we do with all of
our medicines, we will continue to monitor the safety of JANUVIA and will share
the data with regulatory agencies and the medical community,” said John
Amatruda, M.D., senior vice president and franchise head, Diabetes and Obesity,
Merck Research Laboratories.”Patients with type 2 diabetes are more likely
to develop pancreatitis than other people, and as FDA noted in a publication
earlier this year, ‘diagnosis [of drug-induced pancreatitis] poses a challenge
since it can be difficult to rule out other causes.’ Merck would encourage any
patient with concerns to speak with their physician.”

Diabetic Investor can say at this point is here we go again. We should also add
that Diabetic Investor was one of the few, perhaps only publication that warned
everyone that Januvia was not free from serious adverse events.

everyone knows the FDA issued a similar statement with Byetta. And just as they
did with Byetta and pancreatitis, the FDA statement implies there is casual
relationship between Januvia and pancreatitis.  It should be noted that Merck did revise the
label for Januvia and Janumet back in March addressing the pancreatitis issue.
Additionally according to Merck over 18 million prescriptions have been written
for Januvia/Janumet.

In a strange
twist of fate, Merck could actually benefit from the work Amylin (NASDAQ:AMLN)
did when they were facing this same issue.  Amylin went to great lengths to demonstrate that
there was no causal relationship between Byetta and pancreatitis. The company
also correctly noted that patients with diabetes are at increased risk of
pancreatitis. In the case of Byetta they also noted the incidence rate of
pancreatitis with Byetta users was actually lower than the incidence rate of
patients with diabetes. However, there is no question that Byetta sales
suffered due to the FDA’s statement and only now are beginning to recover.

This news
regarding Januvia and pancreatitis couldn’t have come at a worse time for
Merck, who for the first time is facing competition in the DPP-4 space. Onglyza®
a DPP-4 from Bristol Myers (NYSE:BMY) and AstraZeneca (NYSE:AZN) has been
approved by the FDA. While Diabetic Investor doubts that Onglyza will be
marketed as a safer DPP-4 as  this is a
dangerous path as it may turn out that Onglyza carries the same risk of
pancreatitis as Januvia. However, given the popularity of Januvia this news
will surely reach patients and physicians quickly as the mainstream media
outlets will soon be reporting the words Januvia and pancreatitis in the same

Once again
physicians will be facing calls from patients wondering if the medication they
take every day is safe. Once again patients will question the safety of a drug
that was promoted as being free from serious adverse events. Once again we’ll
here calls from critics that Januvia was approved prematurely. Once again the
FDA while doing their job has created more questions than answers by their unwillingness
to provide context to their statements.

Diabetic Investor has never been a huge fan of Januvia, we can sympathize with
Merck as they are about to become another victim of the FDA’s continuing quest
to push back diabetes management to the dark ages. Ever since the Avandia
controversy the FDA appears hell bent on finding any problem, real or perceived,
with drugs used to treat type 2 diabetes. Diabetic Investor had hoped that the
FDA under the new administration would actually follow their mission and use
evidenced based medicine to make decisions. Today’s news is further evidence
that FDA remains clueless as to the impact their statements can have patients
no matter how well intentioned these statements may be.

Today’s news
also must be sending shivers down the spines of the people at Amylin and Novo
Nordisk (NYSE:NVO), both of whom are awaiting approval for their drugs that are
targeted at patients with type 2 diabetes.

Investor had hoped under new direction the FDA would understand the simple
concept of risk/reward. That the agency would realize there is no such thing as
a completely safe drug. That the agency would understand that patients with
diabetes face a multitude of risks. The facts clearly demonstrate that when it
comes to pancreatitis patients with diabetes are at increased risk. It is also
true that is nearly impossible to draw a straight line from taking a particular
drug and developing pancreatitis.

After the
Avandia controversy the FDA opened a can of worms with their new guidelines for
approving any diabetes medication. Besides looking at cardiovascular events the
agency appears to be actively looking for any adverse event no matter how
minor. They are placing an almost impossible hurdle in front of companies who
must be wondering if the inmates are running the asylum.

saddest part of this whole situation is that once again patients are the ones
hurt most. Once again they will question whether or not to take their
medications. Once again they will wonder if any drug they take is safe. Once again
they have another reason not be compliant with their therapy regimen.

When will
the FDA wake up and realize that diabetes is serious condition and that no
medication is free from adverse events? When will the FDA understand the simple
concept of risk/reward? When will the FDA actually follow their stated mission
of using evidence based medicine to make decisions?

for the millions of patients taking Januvia or Janumet and the physicians that
treat them all we can say is; Here we go again.