Domestic patients reached 20 million, 5% of the effective treatment methods, who will "save" rare disease patients?

28 February marks the 15th International Day for Rare Diseases. According to statistics, the number of rare disease patients in the world has exceeded 300 million, and there are about 20 million patients on the mainland. At present, difficult diagnosis and treatment are still the dilemma faced by patients with rare diseases. Most rare diseases require the collaboration of multidisciplinary, multidisciplinary clinical experts and medical genetic experts to accurately diagnose them. In addition to the difficulty of diagnosing, only 5% of rare diseases in the world currently have effective treatments. With a smaller audience, the development of rare disease drugs is even more difficult than that of general innovative drugs. In 2021, "a shot of 700,000 yuan" of rare disease drugs into medical insurance, "every small group should not be abandoned" call for this group to receive attention again. With the participation of more organizations such as the Medical Insurance Bureau, the Drug Regulatory Department, and pharmaceutical enterprises, the accessibility of drugs for rare diseases will be further expanded.

Difficult to diagnose

From the time of illness to diagnosis, Xiaoxue (pseudonym) took a full 14 years. In 1999, Xiao Xue, who had just graduated from college, got up as usual, but suddenly found that the left half of his body could not move, the headache was severe, and he soon lost consciousness. Went to a number of hospitals, Xiaoxue's cause is still not clear. The doctor rescued Xiaoxue from the critical illness through hormone shock therapy, but it was not long before Xiaoxue would suddenly recur.

From 1999 to 2013, Xiaoxue's family traveled to nearly 10 three hospitals in many cities, and was finally diagnosed with optic neuromyelitis spectrum disease (NMOSD) in the Third Affiliated Hospital of Sun Yat-sen University in Guangzhou. Optic nerve myelitis spectrum disease is a rare, lifelong, detenuating autoimmune disease characterized by inflammatory lesions of the optic nerve and spinal cord, with a global prevalence of 1-5/100,000 people/year.

According to the definition of the Medical Genetics Branch of the Chinese Medical Association, rare diseases are diseases with a prevalence rate of less than 1/500,000 or a neonatal incidence rate of less than 1/10,000. Xiaoxue's difficult diagnosis is not unique. The "2022 China Rare Disease Industry Trend Observation Report" (hereinafter referred to as the "Report") jointly released by Frost & Sullivan and the Beijing Pain Challenge Public Welfare Foundation mentioned that according to the Survey of more than 20,000 patients by the China Rare Disease Alliance, 42% of patients have been misdiagnosed, and the average age required from the first medical treatment to diagnosis is 0.9 years, and if it does not include patients who have been diagnosed in the same year, rare disease patients need an average of 4.26 years to be diagnosed.

A doctor from a third-class hospital told the Beijing Business Daily reporter that rare diseases have a low incidence, the medical community may lack research on rare diseases, and there are relatively few doctors who understand rare diseases, and they can only rely on years of experience, literature reports and international cooperation to obtain relevant information, which leads to certain difficulties in diagnosing the diagnosis.

As for the reasons for the difficulty of diagnosing the diagnosis, the report mentions that most rare diseases require the collaboration of multidisciplinary and multi-disciplinary clinical experts and medical genetic experts to accurately diagnose. About 80% of rare diseases are caused by genetic factors, and some rare diseases can be diagnosed by genetic testing. Clinicians with such rare disease diagnosis technology and capabilities are relatively concentrated in the top three hospitals in beijing, Shanghai, Guangzhou, Shenzhen and some provincial capital cities, and many clinicians in third- and fourth-tier cities have great difficulty in independently diagnosing rare diseases due to lack of rare disease-related professional knowledge, lack of clinical experience, and limited technical facilities.

There is medicine to be cured

There are still a large number of unmet clinical needs in the field of rare diseases. According to the report, there are more than 7,000 known rare diseases in the world, and more than 300 million rare disease patients worldwide, of which nearly 20 million patients on the mainland are fighting rare diseases. According to other data, more than 200,000 new patients with rare diseases are added to the mainland every year.

Because it is difficult to recruit enough patients for clinical trials, rare disease drug development is not a small cost for pharmaceutical companies. The characteristics of rare disease drug clinical trials such as small sample size, large heterogeneity, and difficulty in recruitment make the failure rate of any stage of clinical trial significantly higher. Currently, only 5% of rare diseases worldwide have effective treatments.

However, the rare disease patient population is receiving more attention. According to data provided by the president of a multinational pharmaceutical company, since 2018, more than one-third of the world's clinical trials under research have focused on rare diseases, compared with just a dozen percent in previous years.

In order to promote the research and development of rare disease drugs, in January 2022, the State Food and Drug Administration issued the "Technical Guidelines for clinical research and development of rare disease drugs", proposing that the clinical research and development of rare disease drugs, in addition to following the research and development rules of general drugs, should be closely combined with the characteristics of their diseases, on the basis of ensuring rigorous science, adopt a more flexible design, make full use of limited patient data, obtain scientific evidence to meet the assessment of benefits and risks, and support regulatory decision-making. This is regarded by the industry as a relative relaxation of the requirements for clinical trials of rare disease drugs, and continues to promote the research and development of pharmaceutical companies.

Wang Chenguang, director of the Pain Challenge Foundation and former dean of tsinghua university law school, once mentioned in an interview with the Beijing Business Daily reporter that the research and development and production of rare disease drugs still need to have clearer and more active legal institutional arrangements, which can ensure that the pharmaceutical industry, especially pharmaceutical companies, can invest in the research and development of rare disease drugs.

Multi-party cooperation

For patients, from the diagnosis to the availability of drugs, and then to whether the drugs are affordable is another problem in front of them. Xiao He told the Beijing Business Daily reporter that in the two years when Pompeii's disease was just diagnosed, he had not taken medicine. "Can't afford to take medicine" is the most direct reason given by Xiaohe, according to her weight, the cost of a full amount of medicine a year will reach millions. According to Xiaowen, a patient with optic neuromyelitis, the family has spent nearly 800,000 yuan for medical treatment.

The state is also actively promoting the diagnosis and treatment of rare diseases. At the end of 2020, Shandong issued the "Notice on Further Improving the Insurance System for Serious Illnesses", which clarified that for the special efficacy drugs of the three rare diseases included in the scope of payment, such as Gaucher disease, Pompe disease and Fabre disease, the minimum payment standard is 20,000 yuan, 80% of the part below 20,000 yuan to 400,000 yuan, 85% of the part of 400,000 yuan (inclusive), and the maximum payment limit is 900,000 yuan.

In addition, the number of rare disease drugs included in the national medical insurance catalogue has increased year by year in recent years. In 2021, the Nocinasine sodium injection for the treatment of spinal muscular atrophy (SMA) was reduced from nearly 700,000 yuan per injection to more than 30,000 yuan, and Zhang Jinni, a negotiator of the National Medical Insurance Bureau, bluntly said at the scene, "Every small group should not be abandoned."

According to the statistics of the Beijing Pain Challenge Public Welfare Foundation, after the negotiation of the national medical insurance catalogue in 2021, 58 drugs for 28 rare diseases have been included in the national medical insurance catalogue. Based on the statistics of the First Rare Disease Catalogue, the medical insurance catalogue covers more than 60% of the 87 rare disease indications in the mainland. In 2021, The sodium injection of Northinacine into the medical insurance directory has achieved a "zero breakthrough" in the national medical insurance directory of high-value rare disease drugs.

Mao Hua, partner and managing director of Sullivan Greater China, told the Beijing Business Daily reporter that in recent years, the number of rare disease drugs approved has increased, and there are 87 kinds of drugs in China that clearly indicate the indications for rare diseases, involving 43 kinds of rare diseases, of which, as of the end of 2021, after the national medical insurance negotiations, 58 drugs have been included in the national medical insurance, covering 29 rare diseases, and the dawn of the use of Drugs for Chinese patients has appeared.

At the same time, multiple social forces are constantly promoting the protection of rare disease drugs. The "Report" mentions that charitable organizations have driven more social forces to participate in "multi-party payment"; innovative payment platforms have created a multi-level patient service and protection system from the perspective of patients; and commercial insurance has also been continuously explored in the payment of rare disease drug fees.

Beijing Business Daily reporter Yao Qian