Source: bioclub

On August 8, 2023, Aspen Neuroscience announced that its application for a new drug clinical trial (IND) for autologous cell therapy ANPD001 has been approved by FDA in the United States and will start clinical trials soon. It is reported that the treatment by replacing dopamine neurons lost due to the disease to treat PD (Parkinson's disease).

According to World Health Organization (WHO) data, the prevalence rate of PD among people over 65 years old is about 1.7% and that of people over 80 years old is about 3%. And is becoming younger, adolescent PD patients accounted for 10% of the total. According to the statistics of the World Parkinson's Association, there are 5.7 million PD patients in the world, and about 3 million in China. With the gradual intensification of aging, it is estimated that the number of PD patients in China will reach 5 million in 2030, accounting for half of the global number of patients. In addition, according to the data of New thinking Industry Analysis, the anti-PD drug market in China's public hospitals in 2021 was carved up by Boehringer Ingelheim and other foreign drug companies, with a total share of nearly 90%. The remaining 10% is reserved for domestic drugs. It can be seen that for local enterprises, the research and development of PD drugs Brooks no delay. However, it is gratifying that local enterprises have also made generic drugs on the market, and have made breakthroughs in new drug research and development one after another.

On the other hand, the current clinical chemotherapy, physiotherapy and other adjuvant therapy represented by levodopa and DBS can not solve the problem of loss of functional neurons in the brain of patients, and have serious side effects.

Therefore, some domestic and foreign pharmaceutical companies start from cell therapy, trying to solve this problem, the effect is surprising, the cure of PD may no longer be a myth.

Cell therapy is exciting, and there is good news at home and abroad.

Since the 1990s, the discussion and research on the use of cell replacement therapy for PD patients has begun, but the progress has been slow.

At present, there is no treatment in the world that can prevent, replace or prevent the loss of dopaminergic neurons or slow down the progress of PD. The news that Aspen Neuroscience will launch a clinical trial of ANPD001 is undoubtedly encouraging.

ANPD001 is a kind of autologous cell therapy, which can be used as an autologous neuron substitute for PD. The therapy starts with PD and uses induced pluripotent stem cells (iPSC) extracted from patients' skin cells to make dopamine neuronal progenitor cells (DANPCs). Before implanting these cells, strong quality control tests, including genomic tests based on artificial intelligence, are used to assess their potential viability.

Next, Aspen will launch the first phase 1 to 2a clinical trial in patients with moderate to severe PD.

Another piece of good news comes from China. On August 2 this year, the IND application of NouvNeu001, a new PD drug of Ruijian Pharmaceuticals, was formally approved by the State Drug Administration. This is also a universal cell therapy product based on chemical induction, which entered the clinical stage earlier in the field of PD therapy.

NouvNeu001 induced pluripotent stem cells to obtain healthy dopaminergic neural progenitor cells, which can be efficiently transformed into mature dopaminergic neurons and make up for the deficiency of dopaminergic neurons. At the same time, it secretes dopamine transmitters and forms a neural connection with the original neurons in the body, resulting in a comprehensive therapeutic function. From the completed experimental results, after four weeks of administration, not only the behavioral function of all kinds of disease model animals treated with NouvNeu001 has been greatly recovered, but also a number of physiological and biochemical indexes have been significantly improved.

Source: CDE

By contrast, MSK-DA01, a drug derived from embryonic stem cells (ESCs) from Bayer's BlueRock, takes as little as 12 weeks to take effect.

MSK-DA01 is used in the treatment of advanced PD. IND was approved by FDA in 2021 and the completion of phase I clinical safety trials was announced on June 28, 2023.

Domestic new drug LY03003 will be put on the market once every seven days, and salfenamide and opiocarbon will be on the market.

Cell therapy is encouraging, and other treatments are progressing steadily. Recently, Luye Pharmaceutical announced that its application for listing of rotigotin sustained-release microspheres (LY03003) for injection was accepted by the Drug Review Center of the State Drug Administration of China and included in the priority review for the treatment of PD.

LY03003 overcame the non-physiological pulse stimulation produced by short-acting dopaminergic drugs, showed obvious characteristics of sustained-release preparations after intramuscular injection, and maintained a stable release of rotigotene within 7 days. In addition, due to the small range of concentration changes, the adverse reactions caused by LY03003 are also reduced, which improves the compliance of patients to a certain extent.

Source: CDE

Compared with the seven-day frequency of LY03003, Bial Pharmaceuticals' opicapone (trade name Ongentys) has an evaluation rate of once a day. Opicapone is a new generation of peripheral catechol O-methyltransferase (COMT) inhibitor, developed by Portuguese company Bial-Portela. It was approved in Germany and the United States in 2016 and 2020 respectively. Opicapone is the first and only daily COMT inhibitor approved. It can effectively reduce the "off" time of PD patients, increase the "on" time, and there is no movement disorder. Fosun Pharmaceutical subsidiary Jiangsu Wanbang biochemical Pharmaceutical Group Co., Ltd. reached an agreement with Bial on January 9, 2018 to introduce Ongentys's Chinese mainland development rights (excluding Hong Kong, Macao and Taiwan). It is currently in phase III trial. Another PD drug, salfenamide, is expected to be available in China before Opipicapone.

Safenamide is a third generation selective inhibitor for MAO-B. It was approved for the treatment of PD by FDA in 2017. It has the advantages of high selectivity and good safety. It is regarded as an important milestone in the treatment of PD in the United States. Compared with the first and second generation MAO-B inhibitors, salfenamide had higher selectivity to MAO-B and reversible inhibitory effect on monoamine oxidase. The physiological activity of MAO-B could be completely recovered after 8 hours of drug withdrawal. The mechanism of the therapeutic effect of salfenamide on PD is not only through the dopaminergic system, but also by inhibiting the release of glutamate, inhibiting the opening of sodium channel and regulating calcium channel. Multiple action pathways and multiple action targets are regulated together to better play the role of anti-PD.

In April 2022, the application for listing of Safenamide tablets was submitted and accepted in China, and it is expected to be listed this year. In addition, local enterprises that carry out MAO-B indications for PD targets include Jingxin Pharmaceutical and Dongyang Guang Pharmaceuticals.

Source: Kailiying Medicine News, drawing by Shell Society

Dopazide and Praxol take the lead in China, and local pharmaceutical companies accelerate imitation to replace them.

Globally, the five major Parkinson's drugs are rotigotine, Resagilan, L-carbidopa, dopazide and traxidopa. In China's PD drug market, according to Zhongkang CMH data, the anti-PD market of the country's two major channels (hospitals and retail) reached 2.9 billion yuan in 2023, with a compound growth rate of 9%. Compound L-dopasehydrazine continues to take the lead, followed by the dopamine receptor agonist Praxol, which accounts for about 70% of the overall market. Among them, the original research drugs Roche Medoba and Boehringer Ingelheim's Senflo are in the lead. Enta Capone, Piribedil, Resagiran, Slaegilan and so on occupy a place.

Source: Zhongkang CMH, drawing by Shell Society

Dopazide is the most effective symptomatic drug in the treatment of PD, which is called the "gold standard". From the perspective of domestic enterprises, Shandong Xinhua Pharmaceutical, Shanghai Fuda Pharmaceutical and so on have layout, but the market is absolutely high by Roche. In terms of Praxol, Jingxin Pharmaceutical (Soplar), Stone Pharmaceutical Group (Enzhi), Qilu Pharmaceutical (Qilu Pharmaceutical) and other enterprises led the research and development of generic drugs, helping to rapidly increase the market share of generic drugs, breaking the monopoly market situation of the original research drugs, and speeding up the speed of generic drugs replacing the original research drugs.

It is also worth mentioning that on May 8 this year, innovative biopharmaceutical company Hangzhou Changxi Pharmaceutical Co., Ltd. and pharmaceutical company Acorda Therapeutics reached a cooperation on the clinical application of INBRIJA ®(levodopa inhalation powder) in Greater China (Chinese mainland and Hong Kong, Macao and Taiwan). INBRIJA ®is the first inhaled levodopa approved by FDA and has been approved for sale in the United States and the European Union for adult PD patients who are receiving levodopa-dopa decarboxylase inhibitors. The drug is convenient for patients to operate on their own and is suitable for on-demand treatment during the "close" period (OFF episodes).

Conclusion

Source: announcement of pharmaceutical companies, CDE, drawing by Shell Society

At present, drug therapy is still the first choice for PD treatment in China, and the market has been monopolized by foreign investors for a long time. In order to achieve a breakthrough, we need to speed up the improvement of the technology and efficacy of generic drugs. In addition, with the in-depth research of local enterprises, new targets and new therapies continue to emerge, and cell therapy is beginning to show its effectiveness, which is a great surprise to the market and patients. It is believed that the PD cure will be realized in the future.

Reference:

1. "Seventeen anti-Parkinson's disease drugs have been approved and put on the market in China, and there is huge room for growth", People's Daily Health client, 2023-04-11.

2. Using chemically induced iPSC drugs to reverse irreversible "terminal diseases", "Ruijian Medicine" Parkinson's new drug IND approved, 36 krypton, 2023-08-03.

3. "Express | the first one!

A human trial of autologous cell therapy for Parkinson's disease has been approved to replace damaged neurons. "Yao Ming Kant, 2023-08-10.

4. "Green Leaf Pharmaceutical (02186): application for listing of Parkinson's disease drug LY03003 accepted by the State Drug Administration and included in the priority review and approval procedure", Financial circles, 2023-08-01.