Little Orphan Drugs Can Lead to Big Market Rare Disease Drugs in China

-- Third article in the series of articles on rare disease drugs

In the Ice Bucket Challenge in 2014, the "amyotrophic lateral sclerosis" (ALS) patients attracted the world’s attention, and more people started to pay attention to the rare diseases. In the previous two articles in the series of articles on rare disease drugs, the U.S. and EU basic regulations on orphan drugs, and 2017 drug approval situation are separately introduced. Compared to U.S. and EU, the development of rare disease drugs in China is lags far behind.

Support from regulations and policies can be called one of the important factors restricting orphan drug development. Let’s first talk about the regulations, to see the gap between China and the Europe and America in the development process of rare disease drugs.

China

Current situation in China—there have been no explicit official criteria for the determination of rare diseases in China, let alone the independent regulation, and perfect and systematic approval policy on rare diseases, and the medical insurance reimbursement therefor is very little. The current R&D of "orphan drugs" in China can be said to be still in the beginning stages, there are only a few enterprises involving the rare disease drugs, and someone even vividly described the current embarrassing situation of the orphan drugs in China as "three noes". On the other hand, there have been about 20 million rare disease patients in China, and the drugs for rare diseases almost depend on import, therefore, many rare disease patients have no access to drugs, or have to choose the expensive imported drugs.

China and its relevant departments have been actively striving to create favorable conditions for the R&D of orphan drugs in China in recent years, however, the process is slow due to a lack of systematic and strong support. The followings are articles or content involving rare diseases and drugs therefor in the policies and regulations issued in China as collected and arranged by me:

2007: Measures for the Administration of Drug Registration (CFDA Order No. 28)

Article 32 of the Measures for the Administration of Drug Registration specifies that: Where there are circumstances, regarding rare or special diseases, etc., which request clinical sample size reduction or clinical trial exemption, a request shall be made with the clinical trial application, and reviewed and approved by China Food and Drug Administration; Article 45 defines that special review and approval may be implemented for "new drugs for the treatment of diseases such as AIDS, malignant tumors and rare diseases with significant clinical advantage".

2009: Administrative Provisions for the Special Review and Approval of New Drug Registration

The document specifically describes the "special review and approval" in the Measures for the Administration of Drug Registration: for the rare diseases, it specifies that the Center for Drug Evaluation of CFDA (CDE) shall organize an expert meeting to review and determine within 20 days upon receipt of the applications for special review and approval. And applicants who apply for special review and approval shall formulate corresponding risk control plans and implementation schemes at the time of applying for clinical trial and production.

2013: Opinions on Deepening the Reform of the Review and Approval for Drugs to Further Encourage Drug Innovation

It encourages the drug innovation oriented by clinical value, and reiterate that "review shall be accelerated for the registration applications of innovative drugs that have better therapeutic effects for major diseases, rare diseases, and diseases of the old and children, possess independent intellectual property, and are listed in the National Science and Technology Plan and Major Project of China, etc.".

It establishes the fields of generic drugs for priority review. Priority review shall be implemented for the registration applications of generic drugs that are in short supply clinically, the market competition for which is insufficient, that affect the public’s drug use accessibility and affordability, that are for special populations such as children and rare disease patients, and that are recognized as clinical imperative upon marketing value assessment.

2015: Announcement of China Food and Drug Administration on Policies Pertaining to the Review and Approval of Drug Registration (No. 230)

The document defines that separate queuing may be implemented for the "registration applications of innovative drugs for the prevention and treatment of diseases such as AIDS, malignant tumors, major infectious diseases, and rare diseases", to accelerate review and approval.

2016: NHFPC to Establish the First National Rare Disease Diagnosis and Security Expert Committee

On January 4, 2016, the website of the National Health and Family Planning Commission of the People’s Republic of China (NHFPC) released the information that: in order to strengthen rare disease management, promote the normalized diagnosis and treatment of rare diseases, guarantee the basic needs for rare disease drugs, and safeguard the health rights and interests of rare disease patients, the NHFPC would form the Rare Disease Diagnosis and Security Expert Committee under the NHFPC.

The job responsibilities of the expert committee are to: study and propose the definition and scope of rare diseases that conform to China’s national conditions, organize the development of rare disease prevention and treatment technical specifications and clinical pathways, and give suggestions for the prevention, screening, diagnosis and treatment, drug use, recovery, and security, etc. of rare diseases. The expert committee will have a term of office of 3 years from the issuing date of the document.

2016: Opinions on the Implementation of Priority Review and Approval to Resolve Backlogged Drug Registration Applications

It includes the registration applications of pharmaceutical products for the treatment of rare diseases and with significant clinical advantages into the scope of "priority review and approval". For rare diseases or other special diseases, reduction of clinical trial medical case number or exemption of clinical trials may be put forward at the time of applying for clinical trials. CDE shall give review opinions on whether agreeing to the applications according to the technical review needs and realities of the Chinese patients.

2017: Policies on Encouraging Pharmaceutical Product and Medical Device Innovation: Accelerating Review and Approval of Marketing of New Drugs and Medical Devices (Draft for Comment) (No. 52-55)

Document No. 52: Supporting R&D of drugs and medical devices for rare diseases. The health and family planning department shall publish the catalog of rare diseases, and establish the rare disease patient registration system. Applicants of drugs and medical devices for rare diseases may file the application for clinical trial simplification or waiver, to accelerate the review and approval of drugs and medical devices for rare diseases. The drugs and medical devices for rare diseases approved to be marketed overseas may be conditionally approved to be marketed in China, with the relevant research made up in the specified time after the marketing.

Document No. 55: Improving the pharmaceutical product trial data protection system. When filing a marketing application for the pharmaceutical product, an applicant may also apply for the protection of trial data. With respect to innovative drugs approved for marketing, a 6-year data protection period will be granted; with respect to drugs that are both innovative drug and rare disease drug or special drug for children, a 10-year data protection period will be granted; with respect to the rare disease drugs or special drugs for children that belong to improved new drug, a 3-year data protection period will be granted.

The promulgation and introduction of those policies for priority review, clinical trial exemption, and later data protection, etc. partly play a positive role in the development of rare disease drugs, however, those policies are too fragmented and not systematic, and also have no support from strong formal regulations.

On the other hand, we have also seen the pharmaceutical products selected in the publicized catalog of pharmaceutical products for priority review due to reason of rare diseases. In the said catalog published by CDE, there have been 26 applications for rare disease drugs included in the priority review, wherein, 5 are marketing applications, and the rest are clinical trial applications, which is a good start.

Also, the medical security systems for rare diseases have been gradually established and improved in China: Shanghai included the rare disease specific drugs in the coverage of the Mutual Fund of Children Hospitalization in 2011, and started to offer the assistance of not more than RMB 200 thousand to children with rare diseases including Gaucher's disease, Fabry disease, Pompe disease, or mucopolysaccharidosis every year from 2012; the General Office of Qingdao Municipal People’s Government issued the Opinions on Establishing the Urban Serious Illness Medical Assistance System (Trial Implementation) in 2012 to include the rare diseases in the serious illness medical security system in China for the first time; Zhejiang Province started to include the Gaucher's disease, ALS, and phenylketonuria into the medical security system from January 2016 as led by Zhejiang Province Human Resources and Social Security Department; Jiangsu Province has included the drugs for four rare diseases including multiple sclerosis and acute myeloid (promyelocytic) leukemia, etc. into Jiangsu Province list of pharmaceutical products for basic medical insurance and work-related injury insurance; Ningxia Hui Autonomous Region and Kunming have included Cerezyme (imiglucerase for injection) for Gaucher's disease into the coverage of the basic medical insurance.

From the above information and data, we can see that the regulations and technical guidelines on orphan drugs continue to develop in China, however, there is still a gap with the European and American normalized markets. And certainly, we shall also see that China will always overcome difficulties and surpass if the direction is correct. It is hoped that one day, the Chinese patients can access better medical services.

References:

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