Takeda's TAKHZYRO® (Lanadelumab Injection), the World’s First Monoclonal Antibody for HAE, Approved in China, Offering New Hope for Hereditary Angioedema Patients
Dec 04, 2020 18:35
CST Updated
18:35
Takeda
Biopharmaceutical Manufacturer
On December 4, 2020, Takeda China announced today that its innovative drug, Takhzyro® (lanadelumab injection), has been approved by the National Medical Products Administration for the prevention of hereditary angioedema (HAE) attacks in patients aged 12 years and older. Takhzyro® (lanadelumab injection) is currently the only monoclonal antibody (mAb) therapy globally specifically indicated for hereditary angioedema. It reduces the frequency of recurrent edema episodes, prevents asphyxiation due to life-threatening laryngeal edema, improves the quality of life for patients and their families, and fills the gap in long-term targeted treatment for HAE in China.
As the first monoclonal antibody approved globally for the long-term prophylactic treatment of hereditary angioedema (HAE), Takhzyro® (lanadelumab injection) received its initial marketing authorization in the United States in 2018. Pursuant to the “Announcement on Matters Concerning the Optimization of Drug Registration, Review, and Approval” (No. 23, 2018) issued by the National Medical Products Administration and the National Health Commission, for drugs already marketed overseas that are used to prevent or treat severe, life-threatening diseases with no effective therapeutic options, as well as for rare disease drugs, import drug registration applicants may directly submit clinical trial data obtained abroad for drug marketing registration applications if research demonstrates the absence of ethnic differences. Consequently, Takhzyro® (lanadelumab injection) was smoothly approved for entry into the Chinese market within less than two years, thereby enabling this innovative international medication to rapidly benefit HAE patients in China.
Dazyou® (lanadelumab injection) has been recommended as a first-line therapy in the HAE diagnosis and treatment guidelines of the United States and Canada. It can target and inhibit activated plasma kallikrein in patients' bodies, thereby achieving the effect of preventing disease attacks. The primary endpoint of a Phase III clinical study HELP (Hereditary Angioedema Long-term Prevention Treatment Clinical Study™) showed that compared with the placebo group, treatment with a 300 mg dose every two weeks reduced the average number of monthly HAE attacks by 87%. In addition, exploratory study results indicated that during the 16-week steady-state phase (Day 70 to Day 182), 77% of patients in the treatment group receiving 300 mg every two weeks achieved zero attacks, compared to 3% in the placebo group; no treatment-related serious adverse events occurred among treated patients¹.
“Both domestic and international authoritative clinical practice guidelines recommend long-term prophylactic treatment for patients with hereditary angioedema (HAE) to reduce the impact of HAE on patients’ daily lives and prevent life-threatening laryngeal edema.” Professor Zhi Yuxiang from the Department of Allergy at Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, stated, “It is very encouraging to see the rapid approval in China of the first-ever drug for long-term prophylaxis of HAE. Lanadelumab is a monoclonal antibody not derived from human plasma, which can effectively control swelling attacks, bringing HAE patients one step closer to achieving the goal of ‘zero’ angioedema episodes.”
Hereditary angioedema (HAE) is a rare genetic disorder that can be life-threatening, with a reported prevalence of approximately 1 in 50,000 individuals. Due to a deficiency or functional defect of C1 esterase inhibitor (C1INH) in patients, acute edema occurs without warning in multiple body parts, including the extremities, face, genitals, respiratory tract, and gastrointestinal mucosa. This is accompanied by severe abdominal colic, nausea, and vomiting, impairing patients' ability to work and study normally, leading to high rates of depression and anxiety among affected individuals. The most lethal manifestation is edema of the upper respiratory mucosa, which can rapidly progress to cause dyspnea or asphyxia, posing a serious threat to life. Statistics indicate that 58.9% of HAE patients in China have experienced laryngeal edema, with a mortality rate as high as 11%–40%, making it one of the leading causes of death in HAE patients. In May 2018, the National Health Commission, jointly with five other departments, released the "First Batch of the Rare Disease Catalogue," listing hereditary angioedema as one of the first 121 rare diseases.
In China, both the public and physicians have limited awareness of hereditary angioedema (HAE), with an estimated diagnosis rate of less than 5%. Confirmed patients are restricted to long-term use of attenuated androgens or antifibrinolytic agents, which offer limited efficacy in controlling attacks and are associated with numerous adverse effects, including hepatic impairment, osteoporosis, virilization in women, impaired growth and development, and thromboembolism.6 Consequently, many patients refuse medication due to concerns about side effects, leaving them in a prolonged dilemma with no effective therapeutic options.
Ms. Zhang Nan, Head of the Yan Yu Hereditary Angioedema (HAE) Care Center, stated, “I am sincerely delighted for HAE patients in China. As HAE is a rare disease, awareness among both physicians and patients is extremely low, leading to frequent misdiagnosis, missed diagnosis, and inappropriate treatment. It often takes decades for patients to receive a confirmed diagnosis after symptom onset. Even after diagnosis, there were previously no specific therapies available, placing patients at constant risk of life-threatening complications. The recent approval of Takhzyro® (lanadelumab injection) has brought hope to HAE patients for returning to a healthy life. Our greatest aspiration now is to contribute our efforts toward enhancing medical understanding of HAE within society and the general public, particularly among healthcare professionals. We call for more HAE specialists across China and for more hospitals to be equipped with the capabilities necessary for diagnosing HAE.”
Ms. Zhang Nan, Head of the Yan Yu Hereditary Angioedema (HAE) Care Center
“The landmark approval of TAKHZYRO® (lanadelumab injection) fully demonstrates Takeda’s consistent commitment to supporting the hereditary angioedema (HAE) community worldwide. In the future, we will further enhance the accessibility of TAKHZYRO® (lanadelumab injection) in China,” said Mr. Shan Guohong, President of Takeda China. “Benefiting from a series of recent policy reforms by the government to encourage innovative drugs, a growing number of patients can gain early access to important therapies such as TAKHZYRO® (lanadelumab injection). Adhering to our core philosophy of ‘patient-centricity,’ we plan to introduce more than 15 highly innovative medicines within the next five years, helping Chinese patients access global innovations in sync.”
Mr. Shan Guohong, President of Takeda China
As the first monoclonal antibody approved globally for the long-term prophylactic treatment of hereditary angioedema (HAE), Takhzyro® (lanadelumab injection) received its initial marketing authorization in the United States in 2018. Pursuant to the “Announcement on Matters Concerning the Optimization of Drug Registration, Review, and Approval” (No. 23, 2018) issued by the National Medical Products Administration and the National Health Commission, for drugs already marketed overseas that are used to prevent or treat severe, life-threatening diseases with no effective therapeutic options, as well as for rare disease drugs, import drug registration applicants may directly submit clinical trial data obtained abroad for drug marketing registration applications if research demonstrates the absence of ethnic differences. Consequently, Takhzyro® (lanadelumab injection) was smoothly approved for entry into the Chinese market within less than two years, thereby enabling this innovative international medication to rapidly benefit HAE patients in China.
Dazyou® (lanadelumab injection) has been recommended as a first-line therapy in the HAE diagnosis and treatment guidelines of the United States and Canada. It can target and inhibit activated plasma kallikrein in patients' bodies, thereby achieving the effect of preventing disease attacks. The primary endpoint of a Phase III clinical study HELP (Hereditary Angioedema Long-term Prevention Treatment Clinical Study™) showed that compared with the placebo group, treatment with a 300 mg dose every two weeks reduced the average number of monthly HAE attacks by 87%. In addition, exploratory study results indicated that during the 16-week steady-state phase (Day 70 to Day 182), 77% of patients in the treatment group receiving 300 mg every two weeks achieved zero attacks, compared to 3% in the placebo group; no treatment-related serious adverse events occurred among treated patients¹.
“Both domestic and international authoritative clinical practice guidelines recommend long-term prophylactic treatment for patients with hereditary angioedema (HAE) to reduce the impact of HAE on patients’ daily lives and prevent life-threatening laryngeal edema.” Professor Zhi Yuxiang from the Department of Allergy at Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, stated, “It is very encouraging to see the rapid approval in China of the first-ever drug for long-term prophylaxis of HAE. Lanadelumab is a monoclonal antibody not derived from human plasma, which can effectively control swelling attacks, bringing HAE patients one step closer to achieving the goal of ‘zero’ angioedema episodes.”
Professor Zhi Yuxiang, Department of Allergy, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences
Hereditary angioedema (HAE) is a rare genetic disorder that can be life-threatening, with a reported prevalence of approximately 1 in 50,000 individuals. Due to a deficiency or functional defect of C1 esterase inhibitor (C1INH) in patients, acute edema occurs without warning in multiple body parts, including the extremities, face, genitals, respiratory tract, and gastrointestinal mucosa. This is accompanied by severe abdominal colic, nausea, and vomiting, impairing patients' ability to work and study normally, leading to high rates of depression and anxiety among affected individuals. The most lethal manifestation is edema of the upper respiratory mucosa, which can rapidly progress to cause dyspnea or asphyxia, posing a serious threat to life. Statistics indicate that 58.9% of HAE patients in China have experienced laryngeal edema, with a mortality rate as high as 11%–40%, making it one of the leading causes of death in HAE patients. In May 2018, the National Health Commission, jointly with five other departments, released the "First Batch of the Rare Disease Catalogue," listing hereditary angioedema as one of the first 121 rare diseases.
In China, both the public and physicians have limited awareness of hereditary angioedema (HAE), with an estimated diagnosis rate of less than 5%. Confirmed patients are restricted to long-term use of attenuated androgens or antifibrinolytic agents, which offer limited efficacy in controlling attacks and are associated with numerous adverse effects, including hepatic impairment, osteoporosis, virilization in women, impaired growth and development, and thromboembolism.6 Consequently, many patients refuse medication due to concerns about side effects, leaving them in a prolonged dilemma with no effective therapeutic options.
Ms. Zhang Nan, Head of the Yan Yu Hereditary Angioedema (HAE) Care Center, stated, “I am sincerely delighted for HAE patients in China. As HAE is a rare disease, awareness among both physicians and patients is extremely low, leading to frequent misdiagnosis, missed diagnosis, and inappropriate treatment. It often takes decades for patients to receive a confirmed diagnosis after symptom onset. Even after diagnosis, there were previously no specific therapies available, placing patients at constant risk of life-threatening complications. The recent approval of Takhzyro® (lanadelumab injection) has brought hope to HAE patients for returning to a healthy life. Our greatest aspiration now is to contribute our efforts toward enhancing medical understanding of HAE within society and the general public, particularly among healthcare professionals. We call for more HAE specialists across China and for more hospitals to be equipped with the capabilities necessary for diagnosing HAE.”
Ms. Zhang Nan, Head of the Yan Yu Hereditary Angioedema (HAE) Care Center
“The landmark approval of TAKHZYRO® (lanadelumab injection) fully demonstrates Takeda’s consistent commitment to supporting the hereditary angioedema (HAE) community worldwide. In the future, we will further enhance the accessibility of TAKHZYRO® (lanadelumab injection) in China,” said Mr. Shan Guohong, President of Takeda China. “Benefiting from a series of recent policy reforms by the government to encourage innovative drugs, a growing number of patients can gain early access to important therapies such as TAKHZYRO® (lanadelumab injection). Adhering to our core philosophy of ‘patient-centricity,’ we plan to introduce more than 15 highly innovative medicines within the next five years, helping Chinese patients access global innovations in sync.”
Mr. Shan Guohong, President of Takeda China
References:
1，Riedl M A , Maurer M , Bernstein J A , et al. Lanadelumab demonstrates rapid and sustained prevention of hereditary angioedema attacks[J]. Allergy, 2020.
2. National Medical Products Administration and National Health Commission issued the “Announcement on Matters Concerning the Optimization of Drug Registration Review, Evaluation, and Approval,” May 23, 2018, https://www.nmpa.gov.cn/zhuanti/ypqxgg/ggzhcfg/20180523110601517.html.
3，Busse P J , Christiansen S C , Ms M A R , et al. US HAEA Medical Advisory Board 2020 Guidelines for the Management of Hereditary Angioedema[J]. The Journal of Allergy and Clinical Immunology: In Practice, 2020.
4，Betschel S , Badiou J , Binkley K , et al. The International/Canadian Hereditary Angioedema Guideline[J]. Allergy Asthma and Clinical Immunology, 2019, 15:72.
5，TAKHZYRO™ (lanadelumab-flyo) injection prescribing information. Lexington, MA: Shire LLC; 2018.
6. National Health Commission, Office of the Expert Committee on Diagnosis, Treatment, and Assurance for Rare Diseases (Peking Union Medical College Hospital). Guidelines for the Diagnosis and Treatment of Rare Diseases (2019 Edition). 2019:38–189.
7. Yao Xiaojian, Qin Kun, Zhang Tangde. Research progress in the prevention and treatment of hereditary angioedema [J]. Journal of Dermatology and Venereology Diagnosis and Therapy, 2018, 25(1):53-56.
8，Xu YY, Zhi YX, Liu RL, et al．Upper airway edema in 43 patients with hereditary angioedema [J]．Ann Allergy Asthma lmmunof，2014, 112(6): 539-544.
9. National Health Commission, Ministry of Science and Technology, Ministry of Industry and Information Technology, National Medical Products Administration, National Administration of Traditional Chinese Medicine. First Batch of the Catalogue of Rare Diseases, Guo Wei Yi Fa [2018] No. 10. http://www.nhc.gov.cn/yzygj/s7659/201806/393a9a37f39c4b458d6e830f40a4bb99.shtml
10，Reuters (2017). For millions of Chinese with rare disease, some relief in sight. Online access.