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What is CGRP?
CGRP stands for calcitonin gene-related peptide, and it is a
protein that is released around the brain. When CGRP is released,
it causes intense inflammation in the coverings of the
brain (the meninges), and for most migraine patients, causes
the pain of a migraine attack. In fact, if you give CGRP by an
intravenous method to a person with migraine, within four
hours, most of them will get a migraine. That’s the basis of all
the new treatments.
How do the new drugs work and what is
their relationship to CGRP?
Once it was determined that CGRP caused migraine, it became
clear that if we could do something to stop CGRP, we
could probably stop migraine. Four companies decided to
create antibodies against CGRP and against the receptor to
which CGRP binds. These large molecules are called monoclonal
antibodies, and they do not cross into the brain. They
are not eliminated by the liver. In fact, they are such big molecules
that they have to be injected to get into the system. The
drug approved last week, which is called erenumab, the brand
name of which is Aimovig, is a monoclonal antibody against
the CGRP receptor. The additional three are monoclonal antibodies
against the CGRP protein.
What kind of side effects come
with these treatments?
These drugs are extremely well tolerated. In fact, for most
people, they don’t seem to have significant side effects
other than some pain at the injection site.
How fast can one expect to see results?
With these new drugs, the monoclonal antibodies, most patients
who are going to respond will see significant clinical
benefit within a month. They are fast. For typical preventive
medications, we usually work up to the correct dose and then
we wait three months to see whether they’re effective.
How are these drugs administered?
The first three of the treatments are going to be by patient
self-injection with a subcutaneous auto-injector at home.
Some migraine studies estimate that 13 percent of
adults in the U.S. population have migraines, and 2-3
million migraine suffers are chronic. Almost 5 million
in the U.S. experience at least one migraine attack per
month, while more than 11 million people blame migraines
for causing moderate to severe disability.
Two of them will always be monthly, and one of them will be
either monthly or quarterly self-injection. The fourth one is
going to be available by an intravenous infusion, which will
be given every quarter, but patients would have to come into
the doctor’s office to receive the fourth one, which we would
expect at the end of next year or in 2020.
Who will benefit from these treatments?
The monoclonal antibodies have all been studied in episodic
migraine and in chronic migraine and work in both, and
they’re approved by the FDA for both, which is significant.
These treatments are effective for migraine with aura or migraine
without aura, for medication overuse and for no medication
overuse. They have been proven to work in patients
who have had a lack of success in two, three, and four previous
preventive medications.
How much relief can patients
expect to receive?
For patients with episodic migraine, that is less than 15 headache
days per month, the new drugs dropped the number of
migraine days per month by two to four days, generally around
four days. If you multiply four days per month of no migraine
times 12 months, then you have 48 days of no migraine per
year, that otherwise would have been migraine days. That’s
roughly a month and a half of no migraine per year compared
to no treatment.
For the chronic migraine patients, those who have headache
15 or more headache days per month, these drugs dropped
the number of migraine days by six to eight days per month.
Of course, people with chronic migraine have more headache
days per month to begin with, but six to eight days per
month multiplied by 12 means that people could be expected
to have at least two and a half months of no migraine,
even three months of no migraine per year that they previously
had migraine. That’s a pretty dramatic drop in the
number of days of no migraine in a year and per month.
That’s why we’re very, very excited.
Are there any reasons, another question,
for pre-existing health condition or
another medicine that would prevent
somebody from receiving the treatments?
Erenumab, the drug that was approved, has been studied in
patients with angina and heart disease. In that study, there
was no impact on the angina in patients with pretty frequent
angina. Erenumab has also been studied in people
with risk factors for coronary disease and vascular disease
without problems noted. There don’t seem to be any drug
interactions that we know of with these monoclonal antibodies
and other treatments. People would still be able to
use their acute treatments when a migraine breaks through
because for most people, these are not going to completely
eliminate migraines. They’re going to help with frequency,
severity, and duration.
Should people living with migraine approach
this treatment option with caution,
or is it a viable option for most?
I think that the insurance companies are going to limit the access
to these drugs to people who have had a lack of success
with two or three of the conventional preventive medications.
Having said that, the one that was approved, erenumab was
studied in people who had already had two to four preventive
medication failures, and I mean complete failures. These were
people that had taken antidepressants, anti-epilepsy drugs,
anti-blood pressure drugs that were supposed to be effective
for migraine prevention, and they had not worked at all. Then,
they were given the monoclonal antibody, and it still seemed
to work. The other monoclonal antibodies are also being studied
people who have had a lack of success with their previous
preventive treatments, and they also very good in terms of
likelihood of success, even though people have had a lack of
success with previous treatments. This text is for the sake of
visual alighnment beause without it the columns do not line
up. I do hope that I am not making a terrible mess.
Amgen and Novartis have claimed the first approval for
a CGRP inhibitor in migraine, getting an FDA green light
for their Aimovig product ahead of rival drugs from Eli
Lilly, Teva and Alder Biopharma.
Still, I don’t think we would give everybody with migraine this
treatment option, because we’re likely to be limited by insurance
and by cost. The more disabled people, the people that
have tried the hardest and done the most and have still had a
lack of success in reducing their migraines, are the candidates
for whom these medicines should be made accessible.
Are the treatments expected to work for
most migraine cases or for only specific
types of migraine or symptoms?
These monoclonal antibodies were tested for migraine with
aura, migraine without aura, episodic migraine, chronic
migraine, medication overuse headache, and they worked
equally well in every single one of those groups. If you are
somebody who’s very disabled by migraine and has had a lack
of success with prevention and if you currently have commercial
insurance, a monoclonal antibody would be a very reasonable
option.
If these treatments have been said only to
alleviate a few headaches a month. Would
it be worth it for me to try?
It is a gross under-estimate to think that these are only going to
alleviate a few days per month. I think they’re going to reduce
not just the frequency of migraine days per month but the
intensity and the duration of the attacks, and they will likely
help with the acute treatments as well because when people
get their foot off the accelerator, the brake works better. They
have also been shown to reduce the number of acute migraine
treatments people need to take per month.
Are these treatments safe for women who
are pregnant?
I certainly don’t want my patients who go on these to get pregnant.
I am going to ask my patients to have very good birth
control in place before we initiate the treatment. We don’t
know about pregnancy safety, but monoclonal antibody effects
last for months, and I don’t want one of my patients to be
the one to try to find out whether there is a problem.
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