What Everyone should know about Telcagepant – the coming Migraine Drug

As reports continue to come out on the drug telcagepant, the media is abuzz with headlines about a "new era" of migraine treatment.  But how is this drug different, and does it really promise to help a significant number of migrainuers?

really?

When triptans (more about triptans) started to go on the market in the early 1990s, many considered them a miracle drug.  It started with sumatriptan – now commonly known as Imitrex or Imigran  Many with migraine finally found that they could stop an attack with one type or another, and they became truly a new standard in migraine treatment.

Of course, like any drug, triptans aren’t perfect.  Some patients simply don’t respond to triptan treatment.  Others experience side effects such as dizziness, tiredness, or chest and throat tightness.  But most importantly, people with cardiovascular disease or hypertension, or a risk of the same, need to avoid triptans because they constrict blood vessels.

So the theory of telcagepant (previously named MK-0974) is that it can stop a migraine attack (it’s an abortive drug, not a preventative), but with fewer risks and side effects than the triptans generally have.

But will telcagepant deliver?

How triptans and telcagepant stop migraine…

Because the body is such a complicated affair, we’re often unsure exactly why drugs work.  When triptans were first investigated, the focus was on serotonin receptors.  But recent research suggests that triptans don’t work for the reason their developers thought they would.  They actually may work in part by interrupting messages sent via the calcitonin gene–related peptide receptors (CGRP receptors) into the trigeminal nucleus.  (When triptans were first being developed, we didn’t even know what a CGRP receptor was!)

You don’t have to understand how exactly that works, but the interesting thing is that telcagepant is specifically targeted to work on the calcitonin gene–related peptide receptors.  It’s a CGRP receptor antagonist, to be specific.  It stops the normal function of the CGRP receptor.

So, in a nutshell, it’s designed to do on purpose what triptan drugs do "by mistake" – or what they were not specifically developed to do.  (This doesn’t mean they both do exactly the same thing, just that they have one similar function)

But as we said at the beginning, we’re really still learning what migraine does and why each of these drugs work.  They do have a different effect on the body, even though they may do something similar when it comes to migraine (either by stopping an attack at a similar point, or impacting similar chemicals).

Why that’s a good thing

That’s a good thing because we’re developing drugs based on new research, and hopefully drugs that are more "targeted" – so in theory drugs like that should cause less unwanted side effects.  In theory.

Does Telcagepant "work"?

First question, then.  Is the research telling us that telcagepant will work to stop a migraine attack?

The trials so far show telcagepant to be better than nothing (that’s a good start), and comparable to zolmitriptan (also known as Zomig).  Not spectacularly better, but comparable.

As we know from triptans, these medications tend to work differently in everyone.  So, the hope is that telcagepant could be a lot better for people that either can’t take a triptan, or haven’t found any that work for them. (read more on the most recent report on telcagepant)

Fewer side effects?

A common side effect of the triptans was nausea.  That’s a tricky one because, of course, that’s a common migraine symptom too.  However, when triptans compete against telcagepant, it looks like the newer drug will win on this one.  Telcagepant so far seems less likely to cause nausea, and generally seems to have less side effects than at least zolmitriptan.

What about the cardiovascular issues?

This brings us to a key point.  The cardiovascular concerns are why many people can’t take triptans at all.

The idea is that telcagepant will not cause vasoconstriction.  That seems to make it a better candidate.  However, researchers are not ready to give it the green light in this area.

The authors of the most recent study wrote:  …further studies are necessary to determine the safety of telcagepant in patients with cardiovascular disease. Additional studies are also necessary to assess the long-term efficacy and safety profile of telcagepant in patients treating more than 1 migraine attack.

The study that has been done so far is positive.  A couple of small studies (under 30 people) were reported on at the June 2008 meeting of the American Headache Society.  No significant problems were found in patients taking telcagepant.

Not only are more studies needed, researchers want to understand exactly where the CGRP receptors are that are being inhibited.  That will make a big difference when it comes to asking who the drug is safe for.

A new era?

Yes and no.  If this drug is a success, it will hopefully begin a new era of successful drugs that are specifically targeted to fight migraine, something that hasn’t been happening since the triptans came out.

On the other hand, this drug may in the end work in a similar way to the triptans.  There is, in my opinion, much more exciting work going on that will stop the migraine chain reaction at a completely different point.  These drugs may have a much higher chance of helping many more people.  More on those later!

As someone working to help people with migraine, I’m very optimistic that telcagepant will help a certain set of migraineurs that haven’t found good treatment so far.

Should you look forward to telcagepant?  It is certainly something to look forward to if you haven’t been able to take triptans.  It may be something to look forward to if triptans haven’t worked for you.  But there is still work to be done before it arrives on your pharmacist’s shelf.

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