In 2018, an article published in Nature Reviews Drug Discovery showed that the FDA has approved 475 G protein-coupled receptor (GPCR) -related targeted drugs, accounting for 34% of all FDA-approved drugs.
However, these drugs are all small molecules or peptides. The FDA has not yet approved any monoclonal antibody-based GPCR targeted drugs for marketing, and only Japan has previously approved the listing of a GPCR antibody drug targeting CCR4.
GPCR is the largest membrane protein family in the human body, with more than 800 members. At this stage, there are about 370 GPCR proteins that can be drug targets. The target of star drug liraglutide (polypeptide drugs), GLP- 1R, also belongs to the GPCR family. However, members of the GPCR family have a very conservative spatial structure, low natural expression, and difficult to purify. It is difficult to prepare biologically active GPCR antigens, which makes the development of GPCR antibody drugs difficult.
On May 17, the FDA approved Amgenig (erenumab-aooe) for marketing. Patients will be given subcutaneous injections 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 the FDA, sinch CGRP belongs to the GPCR family, which means that Aimovig is the first GPCR antibody drug approved by the FDA .
The efficacy of Aimovig has been confirmed in 3 clinical studies. In the first study, 955 patients with a history of migraine intermittent attacks were compared. The efficacy difference between Aimovig and placebo was compared. After 6 months of treatment, the number of headache episodes per month in the administration group was 1 to 2 days less than that in the placebo group. ; The second study enrolled 577 patients with intermittent migraine attacks. After 3 months of treatment, the average number of headache episodes per month in the administration group was one day less than that of the placebo group. The third study enrolled 667 patients with chronic migraine. For patients with a history of seizures, after 3 months of treatment, the average number of headache episodes per month in the administration group was 2.5 days less than in the placebo group. The most common adverse reactions in the study included injection site reactions and constipation.
Amgen / Novotel jointly share Aimovig's US market rights, pricing its treatment costs at $ 6,900 / year. Express Scripts has previously warned Amgen / Novartis that the cost of treatment of $ 8,000-10,000 / year is unacceptable. As a result, Aimovig's pricing not only made Express Scripts very satisfied, but also far lower than the 8500 estimated by the American Institute of Clinical Economics and Evaluation USD / year.
Apparently, Amgen has learned lessons from the pricing of PCSK9 monoclonal antibody Repatha (Evolocumab)d. Migraine is a tens of billions of dollars in the blue ocean market. Amgen Aimovig ’s first-mover advantage over Eli Lilly and Teva candidate products may not last long, and there is no significant advantage in terms of efficacy. Therefore, choose a price that is easily accepted by all parties. It is Amgen's highest priority to occupy the market as soon as possible.
Symptoms of migraine
Migraine usually shows recurrent mild to severe headaches, which are often intolerable during attacks and severely affect sleep quality. It is also accompanied by nausea, anxiety, depression, etc., which can affect adolescents' social skills and academic performance, and directly cause decline in working capacity. Migraine affects about 10% of the world's population, and the incidence of women is three times that of men. There are approximately 36 million migraine patients in the United States, 8 million patients in Japan, and approximately 13 million patients in China. Because the pathological mechanism has not been fully elucidated, there are still no drugs that can completely cure migraine.
The triptan drugs that appeared in the 1990s only relieved the degree of headaches during migraine attacks and did not prevent migraine attacks. Since then, there have been no breakthrough drugs on the market. In April 2014, the FDA approved the old drug topiramate (approved for the prevention of epilepsy in 1996 and adult migraine in 2004) for the prevention of migraine attacks in adolescents. In 2015, the American Headache Society / American Academy of Neurology Published recommendations for migraine treatment guidelines continue to be triptotans (amotetriptan, eritoran, rosettan, sumatriptan, and zomtriptan), ergotamine derivatives (dihydroergotamine nasal Sprays and inhalants), non-steroidal anti-inflammatory drugs (diclofenac and ibuprofen) and other old medicines, it can be seen that migraine is a disease with far unmet medical needs.
The release level of CGRP increases significantly during migraine attacks, and it is positively correlated with the degree of headache. It is currently considered to be the most potential target for migraine treatment and prevention. Aimovig is the first CGRP monoclonal antibody approved by the FDA, and the first new FDA-approved migraine prevention drug in nearly 20 years. Some optimistic analysts had predicted that the first CGRP inhibitor migraine drug to be launched on the market would have a maximum annual sales of US $ 12.5 billion, and the latter would only total a few billion US dollars.