Amgen Announces Approval Of Aimovig® In Japan For The Suppression Of Onset Of Migraine Attacks In Adults

- Amgen (NASDAQ:AMGN) today announced that the Japanese Ministry of Health, Labour and Welfare has granted marketing approval for Aimovig ® (erenumab) for the suppression of onset of migraine attacks in adults. Aimovig is the first and only approved treatment in Japan to block the calcitonin gene-related peptide receptor (CGRP-R), which is believed to play a critical role in migraine. 3 This is also the first independent submission and approval for Amgen K.K., a wholly owned affiliate of Amgen Inc. headquartered in Tokyo.

"Today's approval further strengthens Amgen's commitment to the migraine community, and we continue to look for ways to expand the availability of Aimovig to help more patients," said Murdo Gordon , executive vice president of Global Commercial Operations at Amgen. "We've seen how much Aimovig has already helped many people living with migraine around the world. Having this treatment approved in Japan will enable us to ultimately serve more patients and help them find the right treatment for this disabling, neurological disease."

Aimovig's approval in Japan is based on results from a Phase II study (20120309) evaluating the safety and efficacy of Aimovig in adult Japanese patients with episodic migraine, and a Phase III study (20170609) evaluating the efficacy and safety of Aimovig in adult Japanese patients with episodic and chronic migraine. In both studies, Aimovig significantly reduced monthly migraine days (MMD) from baseline over months 4, 5 and 6 of the double-blind treatment period (DBTP). ^5,6 The safety and tolerability of Aimovig was also consistent with previously available global data. The most commonly reported adverse reactions include constipation, injection site reactions and somnolence at an incidence of 1% or more. ^5,6

"We were impressed by the Japanese Phase III study (20170609) that showed patients treated with Aimovig saw a reduction from baseline in their monthly migraine days," said Koichi Hirata , M.D., vice president, Dokkyo Medical University. "We believe Aimovig will bring renewed hope to patients by enabling fewer monthly migraine days, and that it will become one of the preferred treatments given its long-term safety and efficacy data."

Migraine is a debilitating neurological condition and can have significant impact on many areas of a person's life. ^1,7 Although approximately 8.4 million people in Japan suffer from migraine, most tend to try and endure the symptoms without seeking help from medical professionals. ^2,8 In Japan , more than 70% of patients with migraine have never visited a hospital to treat their disease, and about 50% of patients try to treat their disease on their own with over-the-counter medications. ⁸

"Migraine is a serious neurological disease, yet is poorly understood in Japan as a condition that requires proper treatment," said Steve Sugino , general manager, Amgen K.K. "We want patients to know they don't need to push through this disease alone. If properly treated with a therapy like Aimovig that has proven efficacy and has an established tolerability profile, they may be able to take on day-to-day tasks and challenges they had previously been forced to give up."

Aimovig (erenumab-aooe) was approved as a preventive treatment for migraine in adults in the United States on May 17, 2018 . As of May 2021 , it has been approved in 71 countries or territories, including the European Union, the United Kingdom , Canada , and Australia , and is approved by many regulatory authorities worldwide. In Japan , Aimovig will be administered subcutaneously in a clinical setting at a dose of one injection every four weeks, consistently from first dose to continuous administration, and likewise after resuming from interruption.

Amgen K.K. became a wholly owned affiliate of Amgen Inc. in the U.S. in April 2020 . It has been co-developing and marketing products in the cardiovascular, oncology, bone, inflammation, neuroscience, and other disease areas, with Aimovig becoming its first independently developed product for patients in Japan .

About the 20120309 Study
The 20120309 study is a Phase II, randomized, placebo-controlled study comprised of a six-month (24 weeks) DBTP that evaluated the safety and efficacy of erenumab for the prevention of episodic migraine in adult Japanese patients. Participants were randomized to receive subcutaneous administration of placebo or erenumab 28 mg, 70 mg or 140 mg once every four weeks for six months. The primary endpoint was the change from baseline in mean MMD over months 4, 5, and 6 of the DBTP. ⁵

About the 20170609 Study
The 20170609 study is a Phase III, randomized, placebo-controlled study comprised of a six-month (24 weeks) DBTP that evaluated the safety and efficacy of erenumab for migraine prevention in adult Japanese patients with episodic or chronic migraine.  There were 261 participants randomized with a 1:1 allocation to receive subcutaneous administration of placebo or erenumab 70 mg once every four weeks. The primary endpoint was the change from baseline in mean MMD over months 4, 5, and 6 of the DBTP. Secondary endpoints were the proportion of participants with at least a 50% reduction in MMD and the change from baseline in mean monthly acute migraine-specific medication treatment days over months 4, 5, and 6 of the DBTP. ⁶

About Migraine
People with frequent migraine attacks may lose more than half their life to migraine. ^9,10 One attack could last longer than three days. ⁹ They endure debilitating pain, physical impairment, and live in constant dread of the next attack – all of which is compounded by a widespread misperception of the disease. ^1,11 The 2019 Global Burden of Disease Study ranks migraine among the top 10 causes of years lived with disability worldwide. ¹² Migraine is associated with personal and societal burdens of pain, disability and financial cost, and it remains under-recognized and under-treated. ^7,13

IMPORTANT JAPAN PRODUCT INFORMATION

About Aimovig in the U.S.
Aimovig (erenumab-aooe) is the first FDA-approved migraine preventive treatment that targets the calcitonin gene-related peptide (CGRP) receptor, which is associated with migraine. ^3,14 Aimovig has been studied in several large, global, randomized, double-blind, placebo-controlled studies to assess its efficacy and safety in migraine prevention. ^15,16 Aimovig is self-administered once monthly via the easy-to-use SureClick ^® autoinjector, without a required loading dose. ^14,17 More than 3,000 patients participated in registrational trials of Aimovig across four placebo-controlled Phase 2 and Phase 3 clinical studies and their open-label extensions. ^{15,16,18 - 20}

Aimovig is also being evaluated through CATALYST, a comprehensive evidence generation program initiated by Amgen and Novartis that includes over 7,500 patients across ongoing clinical trials and a robust assessment of real-world evidence. Spanning over 39 countries globally, CATALYST clinical trials will explore the role of Aimovig in comparative studies, assessing impact on novel migraine outcomes, understanding predictive biomarkers and investigating Aimovig's use in additional study populations. To date, more than 450,000 patients in the United States and 500,000 patients worldwide have been prescribed Aimovig for the preventive treatment of migraine in adults. ^4,21

IMPORTANT SAFETY INFORMATION REGARDING AIMOVIG U.S. INDICATION
Aimovig ^® (erenumab-aooe) is indicated for the preventive treatment of migraine in adults.

Contraindication: Aimovig ^® is contraindicated in patients with serious hypersensitivity to erenumab-aooe or to any of the excipients. Reactions have included anaphylaxis and angioedema.

Hypersensitivity Reactions : Hypersensitivity reactions, including rash, angioedema, and anaphylaxis, have been reported with Aimovig ^® in post marketing experience. Most reactions were not serious and occurred within hours of administration, although some occurred more than one week after administration. If a serious or severe reaction occurs, discontinue Aimovig ^® and initiate appropriate therapy.

Constipation with Serious Complications : Constipation with serious complications has been reported following the use of Aimovig ^® in the postmarketing setting. There were cases that required hospitalization, including cases where surgery was necessary. The onset of constipation was reported after the first dose in a majority of these cases, but patients also reported later on in treatment. Aimovig ^® was discontinued in most reported cases. Constipation was one of the most common (up to 3%) adverse reactions reported in clinical studies.

Monitor patients treated with Aimovig ^® for severe constipation and manage as clinically appropriate. Concurrent use of medications associated with decreased gastrointestinal motility may increase the risk for more severe constipation and the potential for constipation-related complications.

Hypertension: Development of hypertension and worsening of pre-existing hypertension have been reported following the use of Aimovig ^® in the postmarketing setting. Many of the patients had pre-existing hypertension or risk factors for hypertension. There were cases requiring pharmacological treatment and, in some cases, hospitalization. Hypertension may occur at any time during treatment but was most frequently reported within seven days of dose administration. In the majority of the cases, the onset or worsening of hypertension was reported after the first dose. Aimovig ^® was discontinued in many of the reported cases.

Monitor patients treated with Aimovig ^® for new-onset hypertension, or worsening of pre-existing hypertension, and consider whether discontinuation of Aimovig ^® is warranted if evaluation fails to establish an alternative etiology.

Adverse Reactions : The most common adverse reactions in clinical studies (≥ 3% of Aimovig ^® -treated patients and more often than placebo) were injection site reactions and constipation.

Please see Aimovig ^® full Prescribing Information .

About Amgen
Amgen is committed to unlocking the potential of biology for patients suffering from serious illnesses by discovering, developing, manufacturing and delivering innovative human therapeutics. This approach begins by using tools like advanced human genetics to unravel the complexities of disease and understand the fundamentals of human biology.

Amgen focuses on areas of high unmet medical need and leverages its expertise to strive for solutions that improve health outcomes and dramatically improve people's lives. A biotechnology pioneer since 1980, Amgen has grown to be one of the world's leading independent biotechnology companies, has reached millions of patients around the world and is developing a pipeline of medicines with breakaway potential. For more information, visit www.amgen.com and follow us on www.twitter.com/amgen .

About Amgen K.K.
Amgen K.K. is a Japanese operation of Amgen in the U.S., one of the world's leading biotechnology companies. In October 2013 , the company started as Astellas Amgen BioPharma, a joint company with Astellas Pharma, and on April 1, 2020 , became a wholly owned subsidiary of Amgen with a new corporate name. Amgen K.K. focuses on disease areas with significant unmet medical needs, including cardiometabolic, oncological, bone, inflammation/immune and neurological diseases. Currently, approximately 600 employees engage in activities from clinical development to sales with the mission of "To serve patients – Doing everything we can now, for the patients."

Forward-Looking Statements
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Note (Amgen K.K.)

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References

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21. Data on File. Amgen, May 2021

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