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Discussion
about Coenzyme
Q10 and statins
Alena
Langsjoen
Paul
Rosch 2001-10-04
Alena
and Peter Langsjoen
2001-10-04
Bogdan
Sikorski 2001-10-08
Chris
Allen 2001-10-08
Bogdan
Sikorski 2001-10-09
Alena
Langsjoen 2001-10-10
Alena
Langsjoen
Comments
to statement from the International Coenzyme Q10 Association
Thought
I'd let you know that following the recent events regarding serious
side-effects related to the statin, Baycol, the International Coenzyme
Q10
Association has released an official statement which was mailed to the
US
Food and Drug Administration, to the European Agency for the Evaluation
of
Medical Products and to the Japanese Ministry of Health. Peter is
a member
of the Executive Committeee and he is the one who wrote the first draft
of
this letter. Attached is a copy of it in a rich text format.
(This letter is posted at the IQA website at: www.coenzymeQ10.org
Once there click on the "Current Issues" link to view the
letter.)
All my best, --Alena 2001-10-04
Paul J. Rosch
Dear
Peter, Alena et al.
Great letter but would not be surprised if you did not get a response
from the
FDA. I sent a letter along similar lines to JAMA, which they have
now
accepted minus some of the rhetoric such as the "tip of the
iceberg" analogy.
Was disappointed that they rejected Uffe's letter but intend to ask him
if I
can reproduce it in a forthcoming Newsletter that will expand on this
subject. Was not aware that Merck had applied for a patent to
include CoQ10
with their statin product and it would be of interest to learn how they
explained their rationale for this.
2001-10-04 Alena
and Peter Langsjoen
Dear Paul et al,
Below are the abstracts of the patents.....pasted below is what's
available
online (at http://www.delphion.com
), but if you want to read the full
patents, I have hard copies of them and if you're interested, I could
fax
them to you. Actually, I have a cd ROM with all the CoQ10 patents on it
through 1997 or so...you would not believe how many patents there are
assigned to CoQ10! The patents on the cd are in acrobat reader
format and
I supposed that could be emailed? (I know as little about
computers as I
can get away with.)
Anyway, back to statins and CoQ10, there are 2 patents assigned to Merck
(the Nobel Laureate, Michael Brown is the inventor of one of them) and 2
patents assigned to UT Austin (Karl Folkers and Peter's father, Per, are
the inventors on these, but UT Austin owns them), so there are a total
of 4
patents on the combination of HMG-CoA reductase inhibitors & CoQ10.
The US
patent US 5082650, issued in January 21, 1992 is not active anymore (UT
Austin did not pay the fees) and the one issued in 1994 may become
inactive
this fall (for the same reason). It appears that Merck is just
"sitting"
on them, so that noone else would come out with the combination of
statins
&CoQ10!?
So glad to hear that you submitted paper to JAMA on this topic and that
it
was accepted. Be sure to let us know when it will appear! As
far as
hearing back from FDA goes, we're not really counting on that. As
an
Association, we wanted our concerns on statin-induced CoQ10 deficiency
to
be matter of a public record. If we do hear from them, we'll be
sure to
let you know.
2001-10-08 Bogdan
Sikorski
Dear
fellow sceptics
The Statin Position Statement written to FDA should also be sent to the
regulatory
agencies of other countries, which also have some standing globally. And
these include the Swedish one as well as the Australian TGA
(www.health.gov.au/tga).
In my opinion FDA alone will not act on that warning, because it has
very
close
(?) links with its major "stakeholders" (?).Secondly, the letter has been sent to a general
address of the agency, which means it will disappear in a bureaucratic abyss.
Such letters should always be addressed personally, since then the
response
to them becomes a responsibility of a given person, and the
acknowledgement
has to be sent by that person.
So I suggest that the same letter be re-sent to FDA to a
Head of Drug
Approval Section or a similar official. It should also be sent to the
TGA,
addressed to the Principal Medical Advisor - Dr Susan Alder and/or the
Chair of the ADEC
Prof. Tatersal (an advisory body) - details (names) can be found on the
website I have given above. (postal address is PO Box 100, Woden ACT
2606
also on that site).
I have given some thought to that Statin/CoQ10 combination, as to how it
may be handled by the bureaucracy.
In terms of approval for marketing, no agency will approve it before new
clinical studies for the combination are provided, since CoQ10 is also
the
active. So any claim for the active or combination has to be proven
clinically. And that means a lot of money.
It appears that the sponsors have known for some time about the CoQ10
depletion/side-effect problems, but are sitting on the fence awaiting
some
action from the regulatory bodies before they will commit funds for
these
clinical studies, or reveal that the studies have been conducted
showing/addressing problems with CoQ10. They will not however admit that
they knew
because it would mean that they were negligent in their initial
pre-clinical and clinical studies.
After all statins are big money spinners and any loss in confidence
would
mean huge losses in profits. A scare with Bayer was a big enough problem
-
and the response was predictable, reassurances and a huge marketing
attack.
When they will be pushed to the wall by the accumulating evidence on
CoQ10
depletion, new studies will be done or published and the new formulation
with CoQ10
will be rushed to the market as a priority, thus saving them big money.
It
also means that no questions about the validity and the logic of the
treatment with statins will be raised at the time. The companies will
then
be on the fresh run of patents and many years of huge profits to come. 2001-10-08
Chris Allan
Hello
All:
Just some thoughts.
It would seem that any clinical study using a statin/CoQ10 combination
would
require a CoQ10 only arm. In the US the FDA now requires a
separate arm for
vaccine adjuvants without the antigen present. Perhaps this same
philosophy
would permeate the statin trials with CoQ10. If so, this would also
reveal
the benefit of CoQ10 in treatment of heart disease (and Cancer),
assuming
the trial end points were properly outlined. This might tend to make it
difficult for the manufacturers to justify the combination of statins
and
CoQ10. My guess is that the trial endpoints will be designed to be sure
that
there is no possibility that a CoQ10 arm looks useful.
2001-10-09
Bogdan
Sikorski
Chris Allan Wrote:
1. It would seem that any clinical study using a statin/CoQ10 combination
would require a CoQ10 only arm. In the US the FDA now requires a separate
arm for vaccine adjuvants without the antigen present. Perhaps this same
philosophy would permeate the statin trials with CoQ10.
Not necessarily so. The sponsor would probably be able to get away with a
toxicity studies for CoQ10, if they decide to admit (based on the
accumulated evidence) that statins cause depletion of endogenous CoQ10.
Therefore the CoQ10 would be approached as a supplement or sort of active
excipient. After all many agencies, including the one I work for, consider
CoQ10 as a complementary medicine (kind of vitamin) or food (FDA).
2. If so, this would also reveal the benefit of CoQ10 in treatment of heart
disease (and Cancer), assuming the trial end points were properly outlined.
This might tend to make it difficult for the manufacturers to justify the
combination of statins and CoQ10.
I am very surprised that thus far TGA has not received application for
registration of CoQ10 for cardiac indications. And the reason is probably
very simple. No controlled clinical trials/studies showing the benefits of
CoQ10 have been conducted. In Australia, and probably in many other
countries, CoQ10 is available, but the indication is very soft - "aids
in
energy production" - because it is a listed, rather than registered,
substance. In Australia, the use of registered substance must be supported
by clinical evidence, which has to be reviewed by the TGA during approval
process.
Therefore the likelihood of CoQ10 being registered for cancer or cardiac
diseases is very low, or virtually nil. Who is going to pay for such
clinical trials when there is no patent to make money from.
3. My guess is that the trial endpoints will be designed to be sure that
there is no possibility that a CoQ10 arm looks useful.
In such cases, a sponsor approaches a regulatory agency (typically FDA) for
advice, on how to conduct the trials and what endpoints would satisfy FDA
or EU agency, without spending too much time and money to show
"unnecessary
benefits".
2001-10-10 Alena
Langsjoen
Dear Bogdan, Chris, et al,
Peter and I are leaving for a trip to Tokyo and therefore haven't had time
to respond to your latest. We're pretty stressed out about leaving the
family at this time but hopefully nothing terrible here or overseas will
happen while we're away. Anyway, for now, I thought I would briefly
comment that there have been numerous controlled studies performed with
CoQ10 in heart disease over the years, most of them with positive results.
Peter has carefully studied the studies with negative (or should I say
rather 'neutral') results and concluded that it almost appears that they
were, as Chris says, 'designed to fail'. I have a fairly complete list
of
them all and am attaching it in Word as well as plain text files. Later
(after we return from Tokyo), if you'd like, I can put together a list of
abstracts of most of them. Also, below is an abstract of a
meta-analysis
of controlled studies of CoQ10 in CHF.
-------------------------------------
Soja AM, Mortensen SA.
Department of Medicine, County Hospital Sct. Elisabeth, Copenhagen,
Denmark.
The purpose of this was to investigate the effect of coenzyme Q10 (CoQ10)
in patients with congestive heart failure (CHF) by measuring the possible
improvement of certain relevant hemodynamic heart parameters. A statistic
aggregation method know as a meta-analysis was used to measure the changes
in the cardiac parameters. To begin with we collected the total number of
randomized controlled trials and from a total of 14 studies published in
the period of 1984-1994, eight studies met our inclusion criteria. The rest
were excluded because of a lack of data which made a meta-analysis
impossible. The relevant effect parameters investigated were stroke volume
(SV), cardiac output (CO), ejection fraction (EF), cardiac index (CI), end
diastolic volume index (EDVI), systolic time intervals (PEP/LVET) and total
work capacity (Wmax). Seven meta-analyses were performed, one for each of
the parameters, and the calculated effect sizes were all positive.
Statistical significance could be demonstrated for all of the parameters
except the PEP/LVET and Wmax thereby indicating an improvement of greater
or lesser magnitude in the CoQ10 group as opposed to the placebo group.
Accordingly, the average patient in the CoQ10 group had a better score with
regard to SV and CO than 76 and 73% respectively of the patients in the
placebo group. In conclusion, supplemental treatment of CHF with CoQ10 is
consistent with an improvement of SV, EF, CO, CI and EDVI. Homogeneity
could be established for SV and CO. Additional clinical trials of the
effect of CoQ10 on CHF are necessary, but, on the basis of the evidence
currently available, the possibility remains that CoQ10 will receive a
well-documented role as an adjunctive treatment of CHF.
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