FDA approved the first GPCR antibody drug! The first migraine prevention drug in 20 years, with a peak sales forecast of US $12.5 billion

Source: according to an article published in Nature Reviews Drug Discovery on May 21, 2018, there are 475 FDA approved GPCR related targeted drugs, accounting for 34% of all FDA approved drugs [1] However, these drugs are small molecules or polypeptides FDA has not approved the listing of any McAb targeted GPCR drugs Only Japan has approved the listing of GPCR antibody drugs targeting CCR4 before (see the table below) This is also one of the reasons why Hongyun Huaning, a Chinese innovative drug company that develops GPCR antibody new drugs, is regarded as one of the targets of the special article "exclusive · China's top 10 innovative drug companies in 2018" GPCR antibody drugs under research in the world [1] Note: as of June 2017, GPCR is the largest membrane protein family in the human body, with more than 800 family members At present, there are about 370 GPCR proteins that can become drug targets, and GLP-1R, the action target of star drug lilalutide (peptide drugs), is also a GPCR family However, GPCR family members have very conservative spatial structure, low natural expression, membrane protein is not easy to purify, and it is difficult to prepare bioactive GPCR antigen, which makes the development of GPCR antibody drugs very difficult On May 17, the FDA approved the listing of aimovig (erenumab aooe), a company of Amgen The patients were injected subcutaneously once a month to prevent migraine in adults It should be noted that aimovig is the first calcitonin gene related peptide (CGRP) antibody drug approved by FDA, because CGRP belongs to GPCR family protein, which also means aimovig is the first GPCR antibody drug approved by FDA The efficacy of aimovig was confirmed in three clinical studies In the first study, 955 patients with history of migraine intermittent attack were compared with those of placebo After 6 months of treatment, the number of headache attack days in the administration group was 1-2 days less than that in the placebo group on average; in the second study, 577 patients with migraine intermittent attack were 1-2 days less than that in the placebo group on average; in the third study, after 3 months of treatment, the number of headache attack days in the administration group was 1 day less than that in the placebo group on average 667 patients with history of chronic migraine attack were enrolled in the study group After 3 months of treatment, the number of headache attack days per month in the administration group was 2.5 days less than that in the placebo group The most common adverse reactions in the study included injection site reactions and constipation Amgen / Novartis jointly enjoy the U.S market rights of aimovig, pricing the treatment cost of aimovig at $6900 / year Express scripts had previously warned Amgen / Novartis that the $8000-10000 / year treatment fee is unacceptable As a result, aimovig's pricing not only satisfied express scripts, but also far lower than the estimated $8500 / year of the US Institute of clinical economics and evaluation Obviously, Amgen has learned a lesson from the pricing of PCSK9 monoclonal antibody repatha (evolocumab), a key product Migraine is a blue ocean market with tens of billions of dollars The first mover advantage of Amgen aimovig compared with Lilly and Teva candidate products may not be maintained for a long time, and there is no significant advantage in efficacy Therefore, Amgen is most important to choose a price that is easily accepted by all parties to occupy the market as soon as possible Migraine is a recurrent mild to severe headache It usually suffers from headache It can seriously affect sleep quality, and nausea, anxiety and depression will affect the social skills and academic performance of adolescents It will directly lead to the decline of the ability of adults to affect the ability of the whole population, which affects about 10% of the population worldwide, and the incidence rate of women is 3 times that of men There are about 36 million migraine patients in the United States, 8 million in Japan and 13 million in China As the pathological mechanism has not been fully elucidated, there is still no drug that can completely cure migraine The traptan drugs appeared in 1990s are only to relieve the headache degree of migraine attack, and can not prevent migraine attack No breakthrough migraine drugs have been on the market since triptan In April 2014, the FDA approved topiramate (approved for epilepsy prevention in 1996 and migraine prevention in adults in 2004) as a new drug to prevent migraine attack in adolescents In 2015, the new migraine treatment guidelines issued by the American Headache Society / American Academy of Neurology still recommended tripotan (amoctan, iritraptan, rotrtan, sumatriptan and zolmitrotan) It can be seen that migraine is a kind of disease whose medical demand is far from being satisfied CGRP release level was significantly increased during migraine attack, and was positively related to the degree of headache It is currently considered as the most potential target for migraine treatment and prevention Aimovig is the first CGRP McAb approved by FDA and the first migraine prevention drug approved by FDA in recent 20 years Once optimistic analysts predicted that the highest annual sales volume of CGRP inhibitor migraine drugs could reach 12.5 billion U.S dollars, while the total sales volume of the latter was only several billion U.S dollars.