CGRP drugs remain highly promising.

CGRP migraine drugs remain on track to get an approval from the FDA within two years. My first post on these drugs appeared in 2007. The first product in this family was tested for the prevention and acute treatment of migraines. It reached the final phase 3 trials and was found to be very effective and safe, but a few patients developed minor liver abnormalities on blood tests. In view of these blood test abnormalities, the manufacturer, Merck decided against completing the trials. A similar medicine, also in a tablet form, is now being developed by Allergan (maker of Botox) and it appears to be free of liver problems.

CGRP (calcitonin gene-related peptide) is a chemical that is released in the brain during a migraine attack. Four companies are targeting the CGRP molecule in a different way. Instead of taking a pill during an attack or daily to prevent migraines, they are developing monoclonal antibodies which bind to the CGRP molecule or its receptor and block its action. These drugs are given by injection. Three of the companies, Amgen, Eli Lily, and Teva are testing intramuscular injection every month, while the fourth one, Alder is testing intravenous administration every three months. Eli Lily is also testing their compound for the treatment of episodic cluster headaches.

To date, there have been several thousand patients exposed to these monoclonal antibodies in clinical trials. What is most surprising to me is their outstanding safety. The side effects have been infrequent and mild. All four companies are conducting large-scale phase 3 trials, which will hopefully confirm their safety. Based on the previous studies, there is little doubt that these studies will show that the drugs are highly effective in preventing migraines. Unfortunately, it will be at least two years before these truly innovative medications become available.

While I am very excited about getting a new and a very different treatment for migraine and cluster headache sufferers, my enthusiasm is tempered by the potential cost of these drugs. Business experts project the cost to be between $12,000 and $18,000 a year. By comparison, the $6,000 yearly cost of Botox injections seems cheap. Only about 100,000 out of several million chronic migraine sufferers have been treated with Botox since it was approved for migraines 6 years ago. This is in large part due to the difficulties in getting approval from the insurance companies. Besides extensive paper work from the doctor, they require that the patient first try and fail two or three preventive drugs. The new CGRP drugs are likely to be the last option in this chain and will require even more paperwork. The result is likely to be a great underutilization of these breakthrough drugs, just as it has been happening with Botox.

I am not suggesting that these drugs should be cheap since literally billions of dollars will have been spent by the time these drugs receive approval. If the companies cannot make a profit, the investment in research will dry up and fewer breakthrough drugs will be developed. This is why most new treatments are developed in the US and not Europe, where drug costs are controlled by the government. Hopefully, in a few years the cost will drop as it has happened with another family of highly effective migraine drugs, the triptans.