Source: YAOZHI Network
Recently, the National Medical Products Administration released the delivery information of drug approval certificates,Jiangsu Aosaikang Pharmaceutical Co.,Ltd., Chia Tai Tianqing Pharmaceutical Group Co., Ltd., Qilu Pharmaceutical Co., Ltd. and Sichuan Kelun Pharmaceutical Co., Ltd.The eltrombopag ethanolamine tablets were simultaneously approved, which is equivalent to passing the quality and efficacy consistency evaluation for generic drugs.
This marks the simultaneous emergence of four winners in the race for the first generic version of the ITP drug Eltrombopag Ethanolamine Tablets.
In 2017, Novartis' original research drug Eltrombopag Olamine Tablets was approved for marketing in China (brand name: Revolade), for the treatment of ITP. By 2022, its sales had exceeded 2 billion US dollars (approximately 14.6 billion RMB).
ITP Treatment Drug Battlefield: A 14.6 Billion Yuan Market – Who Will Emerge Victorious?
"The Hematopoietic Miracle Drug" Past EventsPrimary Immune Thrombocytopenia (ITP) is the most common hemorrhagic disease in hematology, characterized clinically by isolated peripheral blood thrombocytopenia without a clear cause (peripheral platelet count <100×10^9/L). Currently, it is believed that the occurrence of ITP is related to the destruction of endogenous platelets by self-reactive antibodies, alterations in cellular immunity, and impaired production capacity of megakaryocytes and platelets. The treatment goals focus on the prevention and management of bleeding.Eltrombopag is a non-peptide oral thrombopoietin receptor agonist (TPO-RA) that stimulates the differentiation and proliferation of human bone marrow cells into megakaryocytes and promotes megakaryocyte maturation by binding to the TPO receptor on the cell membrane, thereby increasing platelet production.Before the advent of eltrombopag, treatments such as high-dose glucocorticoids and splenectomy were used for refractory ITP, but with poor disease control outcomes.Eltrombopag Olamine Tablets, developed and manufactured by GlaxoSmithKline, are a drug for thrombocytopenia in ITP patients. They belong to the class of oral non-peptide TPO receptor agonists (TPO-RA). In November 2008, it was approved as an "orphan drug" in the United States and transferred to Novartis through an asset swap transaction in March 2015. The currently approved indications include ITP, severe aplastic anemia (SAA), and thrombocytopenia in patients with chronic hepatitis C (CHC).In December 2017, Eltrombopag was launched in China under the trade name Revolade. It is currently classified as a National Reimbursement Drug List (NRDL) Category B product, with a specification of 25mg/tablet, suitable for ITP patients over 6 years old. In 2022, the price was adjusted to 4,396 RMB/28 tablets. In 2023, an application for a new indication was filed, applicable to SAA patients who had insufficient response to prior immunosuppressive therapy.Compared with other therapies, eltrombopag has better dosing compliance, can significantly reduce bleeding rates, decrease the frequency of transfusions, and also help improve patients' quality of life.In the "Chinese Guidelines for the Diagnosis and Treatment of Adult Primary Immune Thrombocytopenia (2020 Edition)," the EXTEND study of eltrombopag is considered Level Ia clinical evidence. TPO and its receptor agonists are recommended as Class A treatments for second-line therapy of ITP. The final data from the EXTEND study showed that a significant increase in platelet count can be observed 1-2 weeks after using eltrombopag, with an efficacy rate of 85.8%, and 52% achieving sustained remission. Bleeding symptoms also improved significantly, and safety was comparable to placebo. In addition to ITP and SAA, research on the use of eltrombopag in chemotherapy-induced thrombocytopenia in malignant tumors, non-severe aplastic anemia (NSAA), and post-transplant thrombocytopenia is ongoing. Eltrombopag is currently the only TPO-RA approved in China for pediatric ITP indications, showing good overall tolerability and favorable safety in pediatric applications.Multiple pharmaceutical companies,Competing in the 14.6 Billion MarketThe domestic compound patent CN100423721C for eltrombopag expired in 2021. In addition to the four pharmaceutical companies approved this time,In China, other pharmaceutical companies such as Shandong Jingwei Pharmaceutical, Grand Pharmaceutical, Changzhou Pharmaceutical, Hongyue Technology, and Zhejiang Hisun Pharmaceutical have also filed for Eltrombopag Ethanolamine Tablets.It is worth noting that, in addition to tablets, a dry suspension formulation is also under application.Table 1 Application Status of Other Eltrombopag Generic DrugsData Source: CDE Official WebsiteIn December 2023, CDE proposed to include the listing application of Zeneca Pharmaceutical's Eltrombopag Ethanolamine for Oral Suspension in the priority review, with indications including the treatment of adult and pediatric patients aged 12 years and older with chronic immune (idiopathic) thrombocytopenia (ITP) who have had an insufficient response to treatments such as corticosteroids and immunoglobulins, as well as severe aplastic anemia. The reason is "new types, dosage forms, and specifications of pediatric drugs that meet the physiological characteristics of children."Other TPO-RAs already marketed in China include Hengrui's Hengqu Petapazine Ethanolamine Tablets (brand name: Hengqu). Hengqu is a Class 1 innovative drug independently developed by Hengrui Medicine. In June 2021, it received approval from the National Medical Products Administration for use in adult patients with chronic primary immune thrombocytopenia (ITP) who have an increased risk of bleeding due to thrombocytopenia and clinical conditions and have had poor responses to treatments such as glucocorticoids and immunoglobulins, as well as adult patients with severe aplastic anemia (SAA) who have had unsatisfactory responses to immunosuppressive therapy.Market Analysis of Eltrombopag Generic Drugs
According to the median incidence rate in China, there are approximately 104,600 patients with ITP, about 40% of whom will later move to second-line treatment, accounting for approximately 42,000 people.Based on one-third of the current pricing of Revolade at 4396 yuan per 28 tablets and the minimum daily dose of 25mg, the annual cost per patient amounts to approximately 18,630 yuan.For the ITP indication, the market for generic eltrombopag has approximately 700 million yuan in substitutable demand. As additional indications such as SAA, NSAA, liver disease-related thrombocytopenia, and cancer-related thrombocytopenia are approved, the market for generic eltrombopag is expected to expand further.Data source: "Chinese Guidelines for the Diagnosis and Treatment of Adult Primary Immune Thrombocytopenia (2020 Edition)"Besides Eltrombopag, other TPO-RAs are also competing for this market.Atopicitrab, distributed by Fosun, achieved domestic sales of over 200 million RMB in 2022, while CHIATAI TIANQING's Avatrombopag Maleate received the first domestic generic approval in January 2023. Avatrombopag is also a drug with high evidence level according to the 2019 International Consensus on ITP, comparable to Eltrombopag, and it has no metal chelating group compared to Eltrombopag, making it safer.Currently, the sales revenue of Hengrui's Hengqu in 2022 at China's public hospital terminals has exceeded 200 million yuan.This time, the listing of four domestically produced generic versions of eltrombopag in China has not yet announced pricing, but it will inevitably impact the market share of Revolade and Hengqu.
1. Zhou Xinhui, Ruan Changgeng, He Yang. Research Progress on Primary Immune Thrombocytopenia Induced by Novel Coronavirus[J]. Chinese Journal of Experimental Hematology, 2023, 31(02): 593-597. DOI:10.19746/j.cnki.issn1009-2137.2023.02.0422. Chinese Guidelines for the Diagnosis and Treatment of Adult Primary Immune Thrombocytopenia (2020 Edition) [J]. Chinese Journal of Hematology, 2020, 41(08): 617-623.Follow the official account to get reliable and professional information and analysis.
