BGC20-0166

Sleepdoctor (Michael Rack) alerts us to a new pharmaceutical product in
development: BGC20-0166.  He doesn't say a lot, except to
dismiss it out of hand.  That is appropriate, but I thought
I'd add a bit of explanation.  



His post:

Saturday, May 03, 2008

href="http://sleepdoctor.blogspot.com/2008/05/pills-dont-cure-obstructive-sleep-apnea.html">Pills
don't cure Obstructive Sleep Apnea



The life sciences company BTG is developing a pill that will supposedly
treat obstuctive sleep apnea:



BGC20-0166 is a novel combination of two marketed serotonin modulating
drugs being developed for the treatment of OSA.



Various serotonergic and serotenergic/noradrenergic antidepressants,
including Prozac and protriptyline, have been used to treat OSA. These
medications have a mild effect on osa. They slightly improve osa by
increasing upper airway tone and also possibly by decreasing REM sleep.
The effects are mild and antidepressants are not considered to be an
effective treatment for OSA.



I don't recommend buying stock in BTG.

Posted by Michael Rack, MD at 2:18 PM

So what is this stuff?

Unfortunately, there is very little information that is openly
available, at least that I could find.  There is nothing on
Medline, for example.  



The manufacturer's
site says that "...BGC20-0166 is a proprietary combination of
two marketed serotoninergic modulating drugs..."  It does not
say which drugs are used, nor does it tell us what kind of serotonin
modulation they perform.  Presumably, they are SSRIs.
 



If so, it is almost certain that both products are available as
generics, or will be, by the time BGC20-0166 is ready to come to
market.  It is hard to see why anyone would pay top dollar for
something that can be compounded from generics.  That is the
most obvious problem.



Furthermore, href="http://www.merck.com/mmpe/sec05/ch061/ch061b.html">obstructive
sleep apnea is a condition that has the potential to lead to
life-threatening complications.  We already have treatments
that reduce these risks.  It is not at all clear
that BGC20-0166 has the potential to reduce these risks.
 IF it does not, it would be an inferior treatment.  



The company's press release does provide some positive news:

href="http://www.sleepreviewmag.com/news/2008-04-25_01.asp">Sleep
Apnea Pill Lowers AHI



The development of a drug for the treatment of sleep apnea is coming
closer to offering a pharmaceutical alternative for apnea relief. BTG,
the life sciences company, issued a report of additional details from
its study of BGC20-0166 in subjects with mild to severe OSA, finding
that in 39 subjects who took the drug AHI was reduced by a mean of 40%
with individual responses ranging between 10% and 85%.

AHI refers to the apnea-hypopnea index, which is an indication of how
many times per hour a sleeping person takes a breath that does not move
any (apnea) or enough (hypopnea) air.  



Whenever you use single number to evaluate a disease state, there is a
risk that you will be oversimplifying, missing something critical.
  href="http://www.pulmonaryreviews.com/sep02/pr_sep02_AHIndex.html">How
valid is the AHI?

"There is not much association between the AHI and
anything else--sleepiness, muscle dysfunction," or other markers for SDB
[sleep-disordered breathing], claimed Dr. Sullivan, who heads the Sleep
Disorders Unit at the University of Sydney in Australia. The management
of SDB should hinge on the history, physical examination, and clinical
judgment, he asserted.

The AHI is not useless, but by itself, it does not tell you what you
really need to know.  



Back to the press release:

In this initial proof of concept study, 39 subjects
diagnosed with OSA received placebo, a single agent, or one of two
doses of BGC20-0166 daily for a period of 28 days. Each subject's
apnea-hypopnea index (AHI) was measured in overnight sleep laboratory
polysomnograph studies on days 14 and 28. The primary endpoint was a
reduction in the AHI at day 28. The treatment group receiving the
high-dose combination demonstrated a statistically significant
reduction in AHI compared to subjects receiving placebo at both day 14
and 28.

They describe this as a "proof-of-concept" study.  What they
have proven is that the drug does something, to some extent, in some
patients, and does not kill them.  That proves that it is
worth investigating more, but it is a long way from proving that the
drug is worth anything.



Their summary statement:

"The results from this trial demonstrate the
potential of this pharmacotherapy to decrease sleep apnea in some
patients and to normalize it in others," said sleep expert Dr Thomas
Roth, current director of the Sleep Disorders and Research Center at
Henry Ford Hospital and former president of the National Sleep
Foundation, who is serving as an advisor to the BTG program. "Future
research is needed to more precisely define the role of BGC20-0166 in
the clinician's armamentarium of apnea therapy."

Roth is a reputable guy, so I would take this seriously.  I
think his last statement is literally correct.  To be fair, the
company has not made any claims yet about the safety or efficacy of the
product.  They are saying that it is worth studying some more.



It seems, though, that in the best case, this still would be a niche
product, unless you can demonstrate reduction in risk of cardiovascular
and cerebrovascular complications, comparable to established treatment.
 That niche would be that subset of patients who a) simply do
not comply with positive airway pressure treatment, and
b) are not candidates for surgery.  



The other thing to keep in mind, is that the severity of OSA changes
over time.  The study indicated that at least some patients
got very good results.  But good results in a 4-week study
will not tell you anything about how well a person does over time.
 



The worrisome complications can take decades to develop.  In
my view, the "further research" they need will take a very long time to
do, in order to get enough evidence to be convincing.  The
time required to get that level of evidence could take up most of the
patent life of the product.



So you could say that I am skeptical, but I still want them to go ahead
with the development.  Maybe they will surprise us all.
 It would be great to have pill for OSA.  The ideal
way to treat anything is with a pill, or so said one of my professors.
 It's just that there are a lot of things we don't have pills
for.