Evive Biotech's Ryzneuta BLA Accepted by U.S. FDA, Marking a Milestone for Chinese Biopharma’s Global Breakthrough

Looking back at the past “Golden Decade,” driven by the dividends of domestic pharmaceutical reforms, the pharmaceutical industry has achieved a leap from quantitative expansion to qualitative transformation, with local pharmaceutical companies realizing remarkable high-speed growth. If asked about the next goal for Chinese pharmaceutical professionals, “bringing Chinese innovative drugs to European and American markets” would undoubtedly be one of the most common answers.

After years of accumulation, many Chinese pharmaceutical companies have long set their sights on the world’s largest pharmaceutical market—the United States. Undoubtedly, the U.S. market represents the “poetic ideal and distant dream” for numerous domestic Chinese pharmaceutical firms. The entry of innovative biologics from China into the U.S. market serves as a significant endorsement, signaling that these companies possess the capability to compete alongside major multinational pharmaceutical corporations in the global arena.

However, breaking into the U.S. market is far from easy. After decades of development, the global pharmaceutical market has established a comprehensive access system, with the United States boasting the most robust regulatory framework for new drug approvals and the most mature approval technologies. On average, it takes 15 years and $500 million to bring a new drug from the laboratory to the market in the U.S. Given the stringent norms spanning R&D, registration, manufacturing, and sales, Chinese pharmaceutical companies, often insufficiently prepared, inevitably struggle to adapt to the rules of the U.S. market. While foreign pharmaceutical firms have thrived in China, domestic Chinese companies have rarely delivered impressive results in the U.S., a disparity that is truly lamentable.

Now, we finally welcome Evive Biotech, the first Chinese biopharmaceutical company to have independently completed global Phase I to III clinical trials with its own team, autonomously submitted a Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA), and received formal acceptance.

On May 28, 2021, Y-Biologics, a biopharmaceutical company dedicated to developing novel biologics, announced that the U.S. Food and Drug Administration (FDA) had formally accepted its Biologics License Application (BLA) for Ryzneuta™ (also known as F-627) for the treatment of chemotherapy-induced neutropenia (CIN), marking the first time a Chinese biopharmaceutical company has independently submitted a complete BLA in the United States.

Ryzneuta™ is the world’s first third-generation G-CSF (recombinant human granulocyte colony-stimulating factor-Fc fusion protein) product independently developed by Yiyi Biopharma, indicated for the treatment of chemotherapy-induced neutropenia (CIN). Neutropenia is a common side effect of chemotherapy for various cancers, characterized by low levels of neutrophils, which are infection-fighting white blood cells. Ryzneuta™ works by promoting the proliferation of these critical white blood cells, thereby enhancing the immune system’s ability to combat infections and preventing potential chemotherapy dose reductions and delays that could adversely affect treatment outcomes.

As the first novel biologic drug from China to complete global Phase I to III clinical trials abroad, Ryzneuta™’s global development program, as previously disclosed, encompasses 10 clinical trials. To date, it has enrolled more than 1,200 patients across multiple countries and regions, including the United States, the European Union, Australia, and China. As of now, the global Phase III clinical trials of Ryzneuta™ (NCT03252431 and NCT02872103) have been successfully completed, meeting both primary and secondary endpoints, with F-627 demonstrating significant and sustained clinical benefits for patients in these trials. Featuring a novel structure that offers a unique and naturally long-acting therapeutic option, Ryzneuta™ holds promise for replacing current pegylated G-CSF therapies on the market.

The U.S. FDA’s acceptance of the marketing application for Ryzneuta™ marks a milestone for Yibiopharm in establishing an international fast-track channel for innovative drugs. Yibiopharm has become the first Chinese biopharmaceutical company to submit a Biologics License Application (BLA) to the U.S. FDA as the primary applicant and have it formally accepted. This achievement signifies that the company not only possesses the capability for global new drug research, but also has established comprehensive capabilities in global clinical development, manufacturing, and regulatory submission. Furthermore, it demonstrates that Chinese biopharmaceutical innovators are capable of meeting the stringent regulatory requirements of the FDA and bringing their innovative achievements to the global market.

In fact, over the past two decades, there have been Chinese-made drugs approved by the U.S. FDA for entry into the American market. However, the vast majority of these are small-molecule chemical generics. In the more challenging realm of large-molecule biologics, the number of domestically developed novel drugs that have successfully entered the U.S. market remains zero. Even the PD-1 monoclonal antibodies, which are experiencing a boom in China, have yet to gain approval for the U.S. market.

Domestic pharmaceutical companies have only gradually shifted from a business model centered on the production and sales of generic drugs to one focused on innovative drug R&D in the past decade, with China’s biopharmaceutical industry still in its infancy. The sector was shaken when a well-known domestic biotech failed in Phase III international clinical trials, wiping out over a billion yuan in investments made by pharmaceutical companies over many years. In contrast, Innovent successfully completed its Biologics License Application (BLA) with the help of Eli Lilly. How difficult is it for China’s innovative biopharmaceutical companies to independently “break through” and gain direct access to the international market by meeting the stringent review standards of the U.S. Food and Drug Administration (FDA)?

In practice, differences in regulatory requirements and oversight focus between Chinese and U.S. authorities have made adapting to these divergent approval standards a core challenge for Chinese biotech companies seeking internationalization. Consequently, some Chinese biopharmaceutical firms, represented by Innovent Biologics and Legend Biotech, have opted early on to collaborate with multinational pharmaceutical giants. However, while such partnerships provide substantial resource support, they come at the cost of missed opportunities for these companies to build and strengthen their own teams’ capabilities.

It is not entirely fair to blame companies like Innovent, given that Chinese innovative pharmaceutical enterprises still have relatively limited strength and experience. Regardless of the outcome, those who dare to challenge the most stringent clinical standards of the U.S. FDA are true pioneers. With over 1,000 folders and more than 10 GB of submission materials prepared over two and a half years, Yiai Biopharma has become the first domestic biotech innovator to successfully complete this arduous journey. For Chinese innovative biopharmaceutical companies currently experiencing explosive growth and eager to target international markets, this achievement holds significant pioneering and demonstrative value.

However, even if an innovative biologic successfully reaches the market, pharmaceutical companies cannot rest easy. This is because biologics are extremely challenging to manufacture, giving rise to the adage that “the process is the product.” Maintaining stable, high-quality, and continuous production and supply during the commercialization phase will be another key factor for Ryzneuta™ as it expands internationally and seeks to capture the U.S. market.

In April 2021, the newly built formulation workshop of Yiyi Biotechnology in Beijing successfully passed the on-site production inspection and obtained the Drug Production License issued by the Beijing Municipal Medical Products Administration. Currently, Yiyi Biotechnology possesses comprehensive drug substance and drug product manufacturing bases that comply with the regulations of the U.S. Food and Drug Administration (FDA), the European Medicines Agency (EMA), and the National Medical Products Administration (NMPA). The acceptance of its Biologics License Application (BLA) signifies that Yiyi will obtain GMP certification from the U.S. FDA, while also unlocking dual opportunities for accelerated filing of subsequent new drugs and expansion into global contract manufacturing organization (CMO) services, thereby providing a solid foundation for its commercialization.

Subsequently, Yiyi Biologics also plans to submit a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) and a New Drug Application (NDA) to China’s National Medical Products Administration (NMPA).

What will “Created in China” look like in the future pharmaceutical industry? Yiyi Biopharma has opened up greater possibilities for this vision with its international fast-track channel for innovative drugs.