The Corpus Callosum

New Drug Out, So What Do You Do?

Several bloggers have already commented on Johnson &
Johnson’s new schizophrenia drug, rel="tag">Invega®.  The official
FDA announcement is href="http://www.fda.gov/bbs/topics/NEWS/2006/NEW01534.html">here.
 The first blog post I saw was at href="http://garrettsparks.blogspot.com/2006/12/medicine-jj-wins-fda-approval-for.html">Sparkgrass:
 

I’d hate for somebody to have to come up with, ya
know, a new drug. Not to say that a longer acting atypical isn’t a nice
addition to the palette, but the fact that J&J’s stock is
suddenly worth more because their chemists did some reformulation work
on the weekend is pretty frustrating.

Some href="http://www.furiousseasons.com/archives/2006/12/nami_touts_new_atypical.html">others
were even more skeptical.  After all, at first glance it
appears to be another me-too drug, designed more to extend patent life
than to expand our pharmaceutical armamentarium.  But let’s
take another look and see if there really is something to this, some
real added value…


First of all, what is it?  It is a new chemical entity, href="http://en.wikipedia.org/wiki/Paliperidone" rel="tag">paliperidone.
 It differs from their prior drug, href="http://www.risperdal.com/">Risperdal ( href="http://en.wikipedia.org/wiki/Risperidone" rel="tag">risperidone)
by the addition of a single hydroxyl group.  It is an active
metabolite of risperidone.  So the active ingredient is
different that other available products.  Second, it has a
different delivery system.  It uses the href="http://www.alza.com/alza/oros" rel="tag">OROS
system, which is a clever pill that uses osmotic pressure to cause a
smooth delivery of the drug over a 24-hour period.  

Does that one small chemical change make any real difference?
 The answer, of course, is: it depends.  There are
many examples of drugs with similar chemical structures that have very
different activity and adverse effect profiles.  For example, href="en.wikipedia.org/wiki/Imipramine" rel="tag">imipramine
and
differ by only one chloride atom.  Yet their effects are
demonstrably different.  So it is premature to assume that
there is no significant difference, even though the molecules are so
similar.  

Another thing: paliperidone does not undergo hepatic metabolism (as
noted in the FDA release).  Risperidone is href="http://dmd.aspetjournals.org/cgi/content/abstract/22/1/129">metabolized
in the liver by the addition of that hydroxyl group, which
enables it to be excreted through the kidneys.  For
paliperidone, that step is unnecessary.  Thus, the potential
for drug interactions is greatly reduced.  In my view, that is
a pretty significant difference.  

What about the delivery system?  There are some instances in
which adverse effects are reduced by having drugs delivered at a
constant rate.  In some cases, it may mean that less total
drug has to be given, to achieve the same effect.  

There is more information at href="http://www.schizophrenia.com/sznews/archives/004387.html">Schizophrenia.com
and in a pair of posts at Psychiatric Resource Forum ( href="http://psychiatricresourceforum.blogs.com/my_weblog/2006/10/new_treatment_o.html">1
href="http://psychiatricresourceforum.blogs.com/my_weblog/2006/12/new_treatment_o.html">2).
 The authors at those two sites seem less skeptical about the
product.  

Of course, you never really know until the drug has been out for while.
 Six months would be a fair trial period.  

In general, if there is not a specific reason to use a new drug, it is
best to wait a while before either trying it (for patients) or
prescribing it widely (for doctors).  

What might be a good reason to try it early?  For one, perhaps
you have already tried everything else, and nothing was satisfactory.
 Of perhaps you are taking Risperdal with good results, but
have problems with sedation and nausea.  Maybe the OROS
delivery would enable you to get the same benefit, without the adverse
effects.  Or maybe you take several other medications that
have interactions in the liver, and you want to avoid the potential for
yet another interaction.

Chances are, this will turn out to be an incremental advance, but not
revolutionary.  The main argument against these kinds of
things is that we would rather have companies turning attention and
resources to finding truly new treatments, as opposed to small
refinements of existing ones.

Comments

  1. #1 Greg P
    December 26, 2006

    One calculated aspect of this is the combination of an easily-fabricated drug with a not-so-easily-fabricated “delivery system” to set the bar higher for copycats. Also adds another high-tech PowerPoint slide or two to the presentation on how the drug works.

  2. #2 Jim Henley
    December 26, 2006

    Hm. In 46 years of moderately informed life I never read complaints about pharmaceutical companies developing “me too” drugs. This is the second one I’ve read since Christmas, which was yesterday.

  3. #3 Joseph j7uy5
    December 26, 2006

    The complaint about me-too drugs probably didn’t get into the media much, but it was mentioned in a book written by Marcia Angell a couple of years ago: The Truth About Drug Companies. It was featured in the New York Review of Books, but thereafter vanished into obscurity. The book was notable, though, because it was written by a former editor for the New England Journal of Medicine.

  4. #4 Brian X
    December 27, 2006

    I think the most blatant examples of unnecessary me-too drugs would have to be Clarinex and Nexium — there really is no meaningful difference between loratadine and desloratadine, and the only difference between Nexium and Prilosec (over the counter, and therefore not as profitable) is that Prilosec is racemic omeprazole, while Nexium contains only one particular handedness.

    On the other hand, sometimes it’s a worthwhile thing to do — witness the replacement of terfenadine with fexofenadine. Carrying the drug one step down the metabolism path eliminated a lot of nasty drug reactions (although I suspect a lingering suspicion of the metabolite is part of what is keeping Allegra a prescription drug).