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Signalling molecules (neurotransmitters) whizz around between nerve cells all the time, acting as links to the surrounding environment. One of these signalling molecules is called PACAP or pituitary adenylate cyclase-activating polypeptide. It occurs naturally in the body and, among other things, sends pain signals to the brain. 

In 2009, Prof. Messoud Ashina and his research group at the Danish Headache Centre at Rigshospitalet discovered that PACAP triggers migraine attacks. This discovery has led to the development of a new antibody against migraine, which blocks PACAP.

The results of the recently completed clinical trial have demonstrated that the antibody aimed at PACAP molecules can prevent development of a migraine attack. The promising findings have just been published in the prestigious The New England Journal of Medicine​

Fewer days with migraine

The participants in the study were adults with migraine and prior to the treatment they were suffering an average of about 17 days with migraine a month. The participants were divided into two groups by drawing lots. One group received treatment with the new antibody against PACAP, while the other group had a placebo.

The group receiving the antibody experienced a reduction of six days with migraine a month. To put the results into perspective, the group receiving the placebo experienced a reduction of four days with migraine a month. The additional two days with no migraine make all the difference.  

- The success criterion for placebo-controlled studies is that the medicine being tested has to show a clear statistical advantage in relation to a placebo. That the antibody reduced the number of days with migraine by a further two days is therefore a very promising research result. Looking at experience with CGRP inhibitors, which at the same stage achieved similar results and are now the recommended first choice for preventive migraine treatment in Europe and the US, there is good reason to be very optimistic about this potential new treatment," says Messoud Ashina.

During the clinical trial, the researchers also ascertained that the antibody being tested only had a few, very mild side effects in less than 5% of the participants. 

Based on Danish research

Like medicines against CGRP, development of the PACAP antibody was based on Danish research. Messoud Ashina is proud of the Danish Headache Centre's contribution to the continued development of migraine treatment: 

- It's fantastic to see once again how findings in Danish headache research can result in new a medical treatment for migraine. Drugs against CGRP were largely developed on the basis of trials conducted at the Danish Headache Centre in the 1990s and 2000s. Now we can see that history has possibly repeated itself with this new antibody aimed at PACAP," says Messoud Ashina. 

One step closer, but not yet home

The study was carried out as a so-called phase 2 clinical trial in which the effect of the new antibody against migraine was examined on a small group of patients. The next step is a phase 3 trial to confirm of the effects of the treatment and examine the effects of the antibody in more detail. 

Messoud Ashina hopes that this new antibody against PACAP signalling will open the door to new treatment options for the millions of people suffering from migraine.

- We are at the threshold of a new era within migraine treatment, and targeted therapy against PACAP signalling may provide pain relief for patients who don't benefit from existing treatments," said Messoud Ashina. 

Facts about the study

• 337 adults with migraine took part in the study.  
  
  
• On average, the participants suffered migraine on 16.7 days a month and had tested two-four existing migraine treatments without success.
  
  
• The participants were divided into two groups by drawing lots: One group received the PACAP antibody Lu AG09222. The other group received a placebo. 
  
  
• The antibody group came down to an average of 10 days with migraine a month, while the placebo group came down to about 12 days a month. 
  
  
• The study was carried out in a collaboration between Prof. Messoud Ashina from the Danish Headache Centre at Rigshospitalet, and the Danish pharmaceuticals company, Lundbeck, which developed the Lu AG09222 PACAP antibody.