A while back, I wrote about the new treatment for
that is under
development, href="http://www.nrpharma.com/products/NRP104.htm" rel="tag">NRP104.
The original post is href="http://trots.blogspot.com/2005_02_27_trots_archive.html">here.
In that post, I reviewed the pharmacology of NRP104.
The basic idea is that the company took an old molecule, href="http://en.wikipedia.org/wiki/Dextroamphetamine" rel="tag">dextroamphetamine,
and tacked a molecule of href="http://en.wikipedia.org/wiki/Lysine">lysine
onto it. That renders it inactive, until an enzyme lops off
the lysine. The point is to try to reduce the potential for
NRP104 has moved up the pipeline, and now has
an approvable letter from the FDA. It also has a
real name now: lisdexamfetamine dimesylate. It is so new that
it does not even have a Wikipedia page yet!
What is the point of this exercise? Do we really need another
repackaged version of an old compound?
The answer is yes, but the reason depends on whom you ask.
Abuse of prescription stimulants is a bit of a problem.
estimate (PDF link), about 5.9% of college undergranduates
will take stimulants that were not prescribed for them. How
much of that is enough of a problem to worry about is subject to
debate, but it indicates that there is a porblem.
Shire and their partner, New River Pharmaceuticals, have presented data
showing there is less potential for abuse of lisdexamfetamine
dimesylate, compared to dextroamphetamine. If that turns out
to be the case on the street, so to speak, then it would be an
So if you ask clinicians if there is a need for a new compound, they
would say there is. That is because no clinician wants to act
as an enabler for someone else’s substance abuse.
If you ask the pharmaceutical company, the answer is also yes.
The patent for Adderall has run out. The other
patented stimulants are running out of patent life. But if
something new is going to make it to the market, it has to have some
kind of selling point. A reduced potential for abuse could be
But how different will lisdexamfetamine really be? The data
presented by the company show that drug abusers do not like it as well
as regular amphetamine. They also show that the blood level
of the drug stops going up in proportion to the dose, at doses above
130mg. So, taking very high doses may not make up for the
delay in attaining peak concentration.
There are other data avaiable, which are favorable as well.
of Michigan Substance Abuse Research Center has on their site
PDF on the subject. On page 27, there is agraph
showing that nasal insufflation (snorting) results in nearly undectable
blood levels of dextroamphetamine, at least in rats.
Shire is hoping that the DEA gives the drug a rating lower than
schedule II, but it is not yet know if that will be the case.
The reason that is important, is that prescriptions for
schedule II medications cannot be refilled, and prescriptions cannot be
called in. It is a nuisance for all involved. Just
getting rid of the nuisance factor would make the product more popular
with doctors and patients. From the href="http://www.redorbit.com/news/health/684391/fda_issues_approvable_letter_for_nrp104_lisdexamfetamine_dimesylate_for_the/index.html?source=r_health">press
If NRP104 is approved with a Schedule III, IV or V
or is unscheduled (“favorable scheduling”), Shire will pay New River a
$300 million milestone payment. US operating profit will be divided as
follows: Shire will retain 75 percent of profits for the first two
years following launch, and the parties will share the profits equally
In the event that NRP104 receives a final Schedule
II classification, no milestone payment will be payable by Shire to New
River upon approval. Division of profits will be calculated under an
alternative profit sharing scheme.
If some actual social good comes of it, so much the
better. The thing is, it is difficult to know what
the abuse potential
really is, until the product has been on the market for a while.
Personally, I suspect that they will get a favorable
classification from the FDA, but that will be subject to change.
If the product turns out to be abused widely, the FDA could
(As an aside for those who like the chemistry of this kind of molecule,
Molecule of the Day has href="http://scienceblogs.com/moleculeoftheday/2006/10/lmethamphetamine_would_you_bel.php">a
post on the related compound, l-methamphetamine.)