February 28th is International Rare Diseases Day, and in recent years, the field of rare diseases has increasingly received attention from all sectors. On one hand, top-level design such as national policies and laws has gradually improved, promoting rapid development of the entire industry, which can be described as 'changing with each passing year.' On the other hand, the public is no longer 'ignorant' of rare diseases, and some widely covered news events related to rare diseases have repeatedly brought rare diseases into public view, sparking social discussions.
This article aims to review and sort out the development of rare diseases in China in terms of diagnosis, medication, support, special medical foods, and innovative services. It outlines the problems faced and progress made in this field over the past, and offers an outlook on China's comprehensive service system for rare diseases, hoping to be beneficial to policymakers, advocates, practitioners from relevant institutions, family members of patients with rare diseases, and the general public who are concerned about this issue.
01
Current Diagnosis Status of Rare Diseases in China
The accuracy and timeliness of clinical diagnosis of rare diseases face challenges, and patients often seek medical treatment elsewhere.
Rare diseases are often related to genes and can affect multiple organs and systems. Precise diagnosis requires collaboration among multidisciplinary and cross-professional clinical experts and genetic specialists. The incidence of rare diseases is extremely low, with a wide variety of diseases and complex symptoms. Most medical staff lack knowledge and diagnostic capabilities related to rare diseases, leading to difficulties in diagnosing them, high rates of missed diagnoses and misdiagnoses, and long diagnostic cycles. According to the "2020 Comprehensive Social Survey on Rare Diseases in China," nearly 70% of the 38,634 medical workers believe they do not understand rare diseases. According to a survey by the China Rare Disease Alliance on 33 rare diseases and a total of 20,804 patients, 42% of patients have been misdiagnosed. The average time from the first visit to diagnosis is 0.9 years, and if patients are diagnosed within the same year, they on average need 4.26 years to be diagnosed.
In addition, due to uneven distribution of regional medical resources, patients often seek treatment in other regions, especially in less developed areas. According to the '2020 China Rare Diseases Comprehensive Social Survey', 96.6% of patients in Beijing and 93.8% of those in Shanghai can be diagnosed locally, while 100% of patients in Tibet and 83.7% of those in Inner Mongolia need to go to hospitals outside their province for diagnosis.
In response to the diagnostic and treatment challenges of rare diseases, in February 2019, the National Health Commission selected 324 hospitals with strong capabilities in diagnosing and treating rare diseases and a large number of cases to form a rare disease diagnosis and treatment collaboration network. This network provides relatively centralized diagnosis and treatment for patients with rare diseases and two-way referrals to fully leverage the radiation and driving effect of high-quality medical resources, thereby improving China's comprehensive diagnostic and treatment capabilities for rare diseases. The rare disease diagnosis and treatment collaboration network also provides a reference for patients with rare diseases regarding their healthcare channels. It is reported that more than a thousand patients have been referred through the national rare disease diagnosis and treatment collaboration network, and the average diagnosis time for patients with rare diseases has been reduced from 4 years to 4 weeks.
02
Current situation of rare disease treatment in China
Medication section: Improved accessibility to rare disease medications
Rare disease drug research and development costs are high, and conducting clinical trials is difficult. Previously, orphan drugs overseas rarely considered being filed for approval in China, and there were very few domestic pharmaceutical companies dedicated to rare disease drug research and development. Patients with rare diseases in our country have long faced the dilemma of "having drugs abroad but no locally." To address the urgent medication needs of patients with rare diseases, the Chinese government has introduced a series of policy measures to encourage the research and development and market launch of rare disease drugs, such as priority review and approval for rare disease drugs, tax incentives, etc., and has made certain progress in enriching the variety of rare disease drugs. As of now, 103 drugs have been launched in China, involving 47 rare diseases; among them, 73 drugs have been launched in China and included in medical insurance, covering 31 rare diseases. With more and more rare disease drugs being launched and included in medical insurance, the medication situation for patients with rare diseases in our country continues to improve.
Special Medical Food Section: Multiple rare diseases require lifelong and adequate consumption of special medical foods, but their accessibility faces challenges
Food for Special Medical Purpose (FMP), commonly referred to as special medical foods, are formulated foods specifically designed to meet the special nutritional needs of individuals with restricted eating, digestive absorption disorders, metabolic disturbances, or specific disease conditions. According to the '2023 Report on the Accessibility of Foods for Special Medical Purpose for Rare Diseases,' there are 32 rare diseases in the 'First Batch of Rare Diseases Catalogue' that require the use of FMP for related treatment. Eighteen rare diseases require timely, lifelong, and adequate use of FMP during treatment. FMP is the main and core treatment method in the clinical treatment of these rare diseases. Without timely treatment, patients face serious consequences such as developmental delays or regression, and even death or disability.
According to the '2023 Report on the Accessibility of Special Medical Purpose Formulas for Rare Diseases', a survey was conducted among 855 patients with 17 rare diseases that require the use of special medical foods during treatment. Ninety-two percent of patients reported significant or improved disease treatment progress after using special medical foods. However, patients face challenges in accessing special medical foods, which are reflected in three aspects: availability, affordability, and accessibility to healthcare providers.
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Knowable
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Available for purchase
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affordable
03
Current situation of rare disease protection in China
In February 2020, the Central Committee of the Communist Party of China and the State Council issued the 'Opinions on Deepening the Reform of the Medical Security System'. The 'Opinions' further clarified China's multi-level medical security system: 'A medical security system that takes basic medical insurance as the main body, medical assistance as the bottom line, and complementary medical insurance, commercial health insurance, charitable donations, and medical mutual aid developing together.' At the same time, it was proposed to 'explore a medication security mechanism for rare diseases'. The issue of medication security for patients with rare diseases has entered a new round of policy exploration.
In January 2021, the National Healthcare Security Administration and the Ministry of Finance issued the 'Opinions on Establishing a Medical Security Benefit List System'. The introduction of the benefit list system has further standardized and required local policies regarding rare disease medication security, especially those at the local level. Localities are not allowed to establish other medical security systems beyond the framework of the basic system, and all regions must strictly implement the National Essential Medical Insurance Drug List. Subsequently, the pace of local exploration of rare disease medication security mechanisms has significantly slowed down. Many of the security models proposed by local governments for innovative drugs for rare diseases outside the medical insurance catalog face adjustment and further standardization.
Rare Disease Protection Model (National Level): Based on basic medical insurance, with medical assistance as a backup
Since its establishment in 2018, the National Healthcare Security Administration has implemented a dynamic adjustment mechanism for China's 'National Essential Medical Insurance, Work-related Injury Insurance, and Maternity Insurance Drug List' (hereinafter referred to as the 'Medical Insurance List'), which is adjusted annually in principle. The dynamic adjustment mechanism has significantly shortened the time for new drugs to be included in the Medical Insurance List, ensuring the medication needs of the general public. Some orphan drugs for rare diseases are being included in the 'Medical Insurance List' through negotiations.
From 2019 to 2022, among the 121 rare diseases included in the 'First Batch of Rare Diseases Catalogue', there were 6 rare diseases with 9 drugs, 6 rare diseases with 6 drugs, 7 rare diseases with 7 drugs, and 7 drugs for 6 rare diseases, totaling 29 rare disease drugs included in medical insurance through negotiations. Among the 7 new rare disease drugs added to the national medical insurance negotiation in 2022, the first innovative drug for neuromyelitis optica spectrum disorder (NMOSD), enantolizumab injection, was negotiated and included in medical insurance. The oral drug risdiplas for spinal muscular atrophy (SMA) has also successfully entered the medical insurance catalog, bringing SMA patients from 'having access to drugs' to 'having a choice of drugs'.
Currently, 73 drugs for 31 rare diseases have been included in medical insurance, including 17 Class A drugs and 56 Class B drugs. Class A drugs can be fully reimbursed, while Class B drugs require a portion to be paid out of pocket. The specific reimbursement ratio varies according to local policies and specific drugs, but it is usually between 70% and 80%.
In November 2021, the State Council issued the 'Opinions on Improving the Medical Insurance and Assistance System for Severe and Extraordinary Diseases'. This new medical assistance policy follows the scope of coverage of the treatment list system for medical insurance, clearly linking medical assistance with basic medical insurance and critical illness insurance, and providing a safety net for individuals who bear the cost of out-of-pocket expenses after medical insurance reimbursement for patients in need. The policy proposes: 'Based on the level of economic and social development and the affordability of all parties, explore the establishment of a rare disease medication security mechanism, integrate resources such as medical security, social assistance, and charitable support, and implement comprehensive protection. Establish an incentive mechanism for charitable participation and implement corresponding tax preferences, fee reductions, and other policies.' At the same time, it is necessary to 'support the development of commercial health insurance to meet protection needs beyond basic medical security.'
Rare Disease Coverage Model (Local Level): The core pain point addressed by local coverage is the coverage of high-value drugs for rare diseases not included in the catalog.
Local governments have actively explored mechanisms to ensure access to rare disease medications, focusing on providing coverage for high-value innovative drugs for rare diseases that are not included in the catalog. To some extent, this has alleviated the economic burden on patients who need high-value rare disease drugs. After years of practice, local rare disease medication guarantee mechanisms have gradually formed representative models such as the 'special fund' model represented by Zhejiang and Jiangsu; the 'major illness insurance' model represented by Shandong and Chengdu; and the 'medical assistance' model represented by Foshan. Local governments have actively explored and supplemented the insufficient coverage of basic medical insurance for high-value innovative rare disease drugs, providing practical cases for formulating national-level special policies for rare diseases.
New Direction 1
Inclusive insurance has become a practical and feasible local exploration path
Penghui Supplementary Commercial Health Insurance, commonly referred to as Penghui Insurance, Huimin Insurance, or Urban Customized Insurance, is usually led or guided by the government and underwritten by insurance companies. It provides supplementary medical security for basic medical insurance participants within a certain region. In 2022, more than 250 insurance products have been launched across various regions. Penghui Insurance will become one of the main bodies for covering innovative drugs for rare diseases outside the catalog. Under the guidance of government departments, future Penghui Insurance products will gradually achieve standardized and unified insurance responsibilities for different products within specific regions, especially in the design of specialized insurance responsibilities for rare diseases. On one hand, through the drug negotiation of Penghui Insurance, high-value rare disease drugs that are already on the market in China but not covered by medical insurance will be dynamically included, partially meeting patients' medication accessibility needs. On the other hand, through policy requirements, the maximum claim limit, reimbursement ratio, and pre-existing condition requirements for Penghui Insurance products in rare disease responsibilities will be determined, ensuring the sustainable development of Penghui Insurance while partially meeting patients' continuous and standardized medication needs.
New Direction 2
The power of public welfare and charity has become a 'new proposition' to solve the challenges of security
Improving the medication security for rare diseases also requires coordinated efforts from the government and society. In recent years, China's public welfare and charitable forces have made a series of efforts for the medication security of rare diseases: whether it's patient organizations or foundations, they are trying to alleviate patients' medication burdens by carrying out assistance programs for patients; in addition, other stakeholders related to 'medication,' including pharmaceutical companies and medical institutions, are also actively responding to patients' medication needs through Patient Assistance Projects (PAP); as patients and families, mobilizing relatives and friends to carry out mutual assistance is also a common self-help measure.
04
Development Trend of Rare Disease Industry
Trend 1: The rise of domestic pharmaceutical companies, participating in the introduction, research and development, and imitation of rare disease drugs
Introduction and Research and Development of Rare Disease Drugs:In the past, the rare disease drug market was dominated by multinational pharmaceutical companies. From 2018 to 2022, 27 rare disease drugs (excluding new indications) were launched on the market, of which only 4 were introduced or imitated by domestic companies. Now, more and more domestic pharmaceutical companies are deploying in the field of rare diseases. As of February 2023, 81 rare disease drugs (excluding chemical generic drugs and biosimilars) are in clinical trials or application stages for marketing, with 67% of these drugs independently developed or introduced by domestic pharmaceutical companies.
Imitation of Rare Disease DrugsImitation of marketed orphan drugs is an important means to improve patient access to medications. In October 2019, the National Health Commission, in conjunction with the Ministry of Science and Technology, the Ministry of Industry and Information Technology, the National Medical Products Administration, the National Intellectual Property Administration, and other departments, organized experts to select and demonstrate drugs that had not yet applied for registration due to patent expiration or near-expiration, were in short supply clinically, or were voluntarily declared by enterprises. They issued the 'First Batch of Drugs Encouraged for Imitation' and the 'Second Batch of Drugs Encouraged for Imitation' in February 2021. Drugs included in the encouraged imitation drug list can receive support in clinical trials, consistency evaluation, priority review and approval, etc. The two batches of encouraged generic drug lists total 49 drugs (by generic name), among which 6 are therapeutic drugs from the 'First Batch of Orphan Drugs'.
In recent years, domestic pharmaceutical companies have not only introduced or independently developed rare disease drugs but also actively copied marketed rare disease drugs. Six rare disease drugs on the list of encouraged generic drugs have been replicated, with four varieties having been launched within the past one to two years. In addition, the state has provided favorable policies for rare disease generic drugs. In the 2022 adjustment of the national medical insurance drug list, the application conditions for drugs outside the medical insurance list were increased to include those included in the national encouraged generic drug list. Zhaokew Pharmaceutical's generic drug, treprostinil, used for the treatment of idiopathic pulmonary arterial hypertension, was approved for market launch in March 2022 on the list of encouraged generic drugs. Benefiting from favorable policies, it was included in the 2022 national medical insurance list through medical insurance negotiations.
Trend 2: The global rare disease space has become a hot investment area, with multinational pharmaceutical companies actively deploying through mergers and acquisitions or R&D collaborations.
The expiration of product patents can cause revenue losses for pharmaceutical companies. To better cope with these losses and maintain growth, large multinational pharmaceutical companies need to expand their product pipeline. In addition to accelerating internal innovation, they often need to rely on external mergers and acquisitions or R&D collaborations. In recent years, large multinational pharmaceutical companies have been active in rare disease transactions.
Since the release of the 'First Batch of Rare Diseases Catalogue' in 2018, the development of the rare disease industry in China has entered a fast track, with nearly 50 policies and regulations related to rare diseases. Benefiting from favorable policies, the number and speed of rare disease drugs launched in China have achieved a 'double increase', continuously improving patient access to medications and perfecting the multi-level guarantee system. In the future, under the national top-level design and promotion, we will continue to explore the development path of rare disease drug security and accessibility, and solve the challenges of accessing rare disease medications.
*This article was published on February 25, 2023, in the International Rare Disease Day special issue of China Medical News, page 03.
