Focus on R&D, entrepreneurship to boost new drugs and development

Could Chinese pharmaceutical companies help mass-produce certain drugs to strengthen the global fight against COVID-19 that is already in its third year, and thus show that their products can be game-changers? Such a question won't be dismissed in a jiffy anymore, industry insiders said.

Given the contagious Omicron variants, what might prove effective are mass-produced, low-cost small-molecule oral antiviral drugs that can be stored easily and accessed widely by outpatients, they said.

To that end, Chinese pharmaceutical companies have been making increasing contributions.

For instance, Shanghai Junshi Biosciences Co Ltd, a Chinese innovation-driven biopharmaceutical company, announced in March a global phase-3 trial on the efficacy and safety of VV116, a treatment candidate for moderate to severe COVID-19.

The investigational drug is jointly developed by Junshi Biosciences and several other domestic entities, including Vigonvita Life Sciences Co Ltd and three institutes of the Chinese Academy of Sciences.

A phase-2 clinical trial of VV116 completed in subjects with moderate to severe COVID-19 in Uzbekistan last year showed two different doses of VV116 had favorable safety and efficacy in the treatment of both moderate and severe COVID-19 patients in comparison with standard therapy.

Based on the positive results, VV116 has been approved for the treatment of moderate to severe COVID-19 patients in Uzbekistan in late 2021. Another global phase-2/3 clinical study of VV116 is ongoing for the early treatment of mild to moderate COVID-19 patients.

That is just one example of how biotech and pharmaceutical companies in China, inspired by the national agenda of innovation-driven development, have been ramping up innovation efforts to enhance their research and development activities.

Some of them have been able to conduct world-class R&D on cutting-edge treatments, especially in the biotech sector.

Franck Le Deu, a senior partner with McKinsey & Company, wrote recently on his LinkedIn blog that China has emerged as an important actor in the global biopharma ecosystem, adding a potent additional source of global biopharma innovation and disruption.

Chinese biopharma has very good access to the necessary ingredients for innovation, he wrote in the blog.

China's 2022 Government Work Report said the nation will do more to promote business startups and innovation initiatives and improve the service capacity of entrepreneurship and innovation platforms.

The country needs to promote scientific and technological innovation, to upgrade industries, eliminate the bottlenecks in the supply chain and realize high-quality development through innovation, it said.

Analysts and business leaders said the nation's unwavering efforts to encourage and support innovation have paid off after the State Council, China's Cabinet, released a document on reforming the review and approval system for drugs and medical devices in 2015.

The emphasis on innovation in China will give rise to a new wave of achievements in the industry, they said.

Wei Dong, CEO of EdiGene, a Beijing-based biotech company developing genome-editing technologies, said the biopharma and pharmaceutical industry in China is growing rapidly.

Since 2015, the industry has been elevating its focus from generics to innovation and developing from "me-too" and "me-better" to "first-in-class", grasping the latest trends like the cell and gene therapy, a global hot spot in the industry, he said.

On the one hand, Chinese biotech and biopharma firms focusing on small-molecule therapeutics and/or macromolecular therapeutics are further improving their R&D capabilities and have first-in-class potentials in their pipelines, especially among early-stage programs.

On the other hand, in the field of cell and gene therapy, companies like EdiGene have accumulated enough expertise and experience to translate innovative technologies into transformative therapies.

Jiangsu Recbio Technology Co Ltd, an innovative vaccine company founded in 2012 in Taizhou, Jiangsu province, is among the very few enterprises in the world that can develop novel adjuvants to US Food and Drug Administration standards. An adjuvant is an ingredient used in some vaccines that helps create a stronger immune response.

Recbio's rich vaccine portfolio includes vaccine candidates for HPV (human papillomavirus), shingles, influenza and adults' tuberculosis. Now, it also has a novel adjuvant recombinant COVID-19 vaccine undergoing phase-2/3 clinical trials.

Clinical studies have shown the vaccine candidate's immunogenicity－it is a term that denotes a substance's ability to produce an immune response－is at least comparable to Moderna/Pfizer's mRNA vaccine, and it can induce high levels of neutralizing antibodies against the Delta, Omicron and other COVID-19 variants, said Liu Yong, founder and chairman of Recbio.

Another COVID-19 vaccine Recbio is developing is the world's first lyophilized mRNA vaccine, which can be stored and transported in conventional cold-chain conditions. If this vaccine receives regulatory approvals, it is expected to greatly improve the accessibility of mRNA vaccines.

The vaccine candidate has induced a high-level neutralization response against both the wild-type and the Omicron strains in mice experiments.

"Thanks to supportive government policies, the R&D, production and commercialization of the domestic pharmaceutical industry have been undergoing remarkable positive evolution," Liu said.

"Policy measures that attract high-end talent from overseas, encourage high-tech enterprises to grow and increase financing channels for enterprises, have all provided strong support for companies in the sector, apart from reinforcing the healthy economic fundamentals and growing demand in the health market," he said.

According to Le Deu with McKinsey, the Chinese biopharmaceutical industry's innovation focus has broadened significantly into all major modalities and disease areas.

For nine out of 10 modalities and for nine out of 13 disease areas, Chinese companies are now leading multinational companies in innovation in China's domestic market.

Citing from Global Oncology Trends 2021: Outlook to 2025, a report by health information consultancy IQVIA Institute for Human Data Science, he blogged that China-headquartered companies are developing 18 percent of all early-stage oncology drugs, up from 6 percent in 2015.

Even more striking, the China share is already 13 percent for all next-generation oncology biotherapeutics, he said.

"While we have yet to see much evidence of first-in-class discovery out of China－other than a few green shoots－one could reasonably expect this to change in the midterm," he said in the blog.

Yang Dajun, chairman and CEO of Ascentage Pharma, said the Chinese biotech company's success is a testimony to China's progress in pharmaceutical innovation.

Thanks to the continuously improving regulatory environment and the reform and development of capital markets in China, Ascentage, which was founded in 2009, stepped onto a fast development track in 2015 and was listed in Hong Kong in 2019.

Engaged in developing novel therapies for cancers, chronic hepatitis B and age-related diseases, the company has built a pipeline of eight clinical drug candidates.

It is also the only company in the world with active clinical programs targeting all three known classes of key apoptosis regulators. Apoptosis, or programmed cell death, is a regulated physiological process leading to cell death.

Last year, its self-developed drug olverembatinib received market approval in China as a treatment for adult patients suffering from tyrosine kinase inhibitor or TKI-resistant chronic phase or accelerated phase chronic myeloid leukemia.

Likely to become a best-in-class treatment in the field of drug-resistant CML in the world, the drug has been granted three Orphan Drug designations and a Fast Track designation by the US FDA, and an Orphan Designation by the European Union.

"Pharmaceutical innovation in China is increasingly clinical value-oriented and is in a transition toward developing higher-quality medicines rather than just imitating innovations of others," Yang said.

"To support such upgrades, a continuously optimizing innovation ecosystem is very important. Only with supportive policy measures, facilitating capital markets and growing demand, could enterprises increase innovation capabilities and achieve sustainable and high-quality development," he said.

EdiGene, founded in 2015, currently has four therapeutic platforms and has obtained the investigational new drug application approval in China for ET-01, a gene-editing hematopoietic stem cells therapy for transfusion-dependent beta-thalassemia, a disease with severe unmet clinical needs in southern China.

The company is also developing in vivo RNA editing therapies, based on LEAPER, an RNA base editing technology discovered by its co-founder Wei Wensheng.

At this year's two sessions－the annual sittings of the National People's Congress, China's top legislature, and the National Committee of the Chinese People's Political Consultative Conference－many NPC deputies and members of the country's top political advisory body also made proposals and suggestions on how China should enhance the scientific and industrial innovation systems to improve new drug discovery and development.

Ding Lieming, an NPC deputy and chairman and CEO of Betta Pharmaceuticals Co Ltd, a Hangzhou, Zhejiang province-headquartered pharmaceutical company specializing in oncology, said in his proposal that China must strengthen efforts to enhance innovation ecosystems and encourage co-innovation and co-development of new drugs to increase overall competence of China-developed innovative drugs to catch up with the first-tier players.