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FDA approves first GPCR antibody drug! The first new drug for migraine prevention in 20 years, with a peak sales forecast of $12.5 billion.

An article published by Nature Reviews Drug Discovery in July last year showed that the FDA approved a total of 475 G-protein coupled receptor (GPCR)-related targeted drugs, accounting for 34% of all FDA-approved drugs.

However, these drugs are small molecules or peptides. The FDA has not approved any monoclonal antibody-based GPCR targeted drug market. Until now, only Japan has approved a GPCR antibody drug targeting CCR4 (see table below).

GPCR antibody drugs in research worldwide

Note: Statistics as of June 2017

GPCR is the largest family of membrane proteins in the human body, with approximately 800 family members. There are approximately 370 GPCR proteins that can be used as drug targets at this stage, and the target of the star drug liraglutide (polypeptide drugs) GLP- 1R also belongs to the GPCR family. However, GPCR family members have very conserved spatial structure, low natural expression, membrane proteins are not easy to purify, and biologically active GPCR antigens are difficult to prepare, resulting in difficulty in the development of GPCR antibody drugs.

On May 17th, the FDA approved the Amjin company’s Aimovig (erenumab-aooe) market. Patients are self-administered once a month for the prevention of migraine in adults. It should be pointed out that Aimovig is the first Calcitonin gene related peptide (CGRP) antibody drug approved by the FDA because CGRP belongs to the GPCR family protein, which also means that Aimovig is the first FDA approved GPCR antibody drug. .

The efficacy of Aimovig was confirmed in three clinical studies. The first study enrolled 955 patients with a history of intermittent attacks of migraines and compared the difference in efficacy between Aimovig and placebo. After 6 months of treatment, the average number of headaches per day in the treated group was 1 to 2 days less than the placebo group. The second study enrolled 577 patients with intermittent attacks of migraine. After 3 months of treatment, the average monthly number of headache attack days in the treatment group was 1 day less than that of placebo group; the third study included 667 patients with chronic migraine. In patients with a history of episodes, after 3 months of treatment, the average number of headache episodes per month in the dosing 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/Novartis jointly enjoys Aimovig’s US market rights and priced Aimovig’s treatment costs at US$6,900/year. Express Scripts had previously warned Amgen/Novartis that the treatment cost of 8,000-10,000 dollars per year was unacceptable. As a result, Aimovig’s pricing not only made Express Scripts very satisfactory, but also far below the 8500 estimated by the US Institute of Clinical Economics and Evaluation. USD/year.

Obviously, Amgen has learned lessons from the pricing of the key product of the PCSK9 monoclonal antibody Repatha (Evolocumab). Migraine is a tens of billions of dollars of blue ocean market, and Amgen’s Aimovig may not be able to maintain its first-mover advantage over Eli Lilly and Teva’s candidate products for too long. There is no significant advantage in efficacy, so choose a price that is easily accepted by all parties. Occupying the market as soon as possible is the most important thing for Amgen.

Migraine is characterized by repetitive mild to severe headaches, which usually lead to unbearable headaches, severely affect the quality of sleep, accompanied by nausea, anxiety, depression, etc., and can affect young people’s social skills and academic performance, and directly affect adults. The decline in labor capacity affects about 10% of the world’s population, and the incidence of females is three times that of men. There are approximately 36 million migraine patients in the United States, 8 million in Japan, and approximately 13 million in China. Since the pathological mechanism has not yet been fully elucidated, there is still no drug that can completely cure migraine.

The presence of triptans in 1990s was only a relief from migraine headaches and did not prevent migraine attacks. Since the triptan drugs, there have been no breakthrough migraine drugs on the market. In April 2014, the FDA approved the old drug Topiramate (approved for the prevention of epilepsy in 1996 and approved for the prevention of adult migraine in 2004) to prevent the onset of migraine attacks in adolescents. 2015 American Headache Society/American Society of Neurology New The recommended guidelines for the published migraine treatment guidelines are still the triptans (almotriptan, eletriptan, rotrotriptan, sumatriptan and zolmitriptan), ergotamine derivatives (dihydroergotamine nasal Sprays and inhalants) and old drugs such as non-steroidal anti-inflammatory drugs (diclofenac and ibuprofen) show that migraine is a medical condition that is far from being satisfied.

The level of CGRP release is significantly higher at the time of migraine attack and is positively related to the degree of headache and is currently considered to be the most promising migraine treatment and prevention target. Aimovig is the first CGRP monoclonal antibody approved by the FDA and the first FDA-approved new migraine prevention drug in the past 20 years. Optimistic analysts had predicted that the first-to-market CGRP inhibitor migraine drugs had annual sales of up to US$12.5 billion, while latecomers totaled no more than billions of US dollars.

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