China's Innovative Drugs Hunt for Billion Dollar Molecule

During this year's National People's Congress and Chinese People's Political Consultative Conference, the term "innovative drugs" was included into the government work report for the first time. The Central Economic Work Conference in 2023 emphasized the need to promote industrial innovation through scientific and technological innovation, especially by fostering new industries, new models, and new growth engines with disruptive and frontier technologies, and developing new forms of productive forces. Industry insiders widely acknowledge that the central government has elevated the biomedical industry to an unprecedented level, placing great expectations on it. Pharmaceutical companies in China have lived up to these expectations and developed products with global competitiveness, striving to become "Billion Dollar Molecules". So, how much potential do these benchmark products on the path of innovation have?

Zanubrutinib

When it comes to Billion Dollar Molecules made in China, BeiGene's Zanubrutinibcannot be ignored. Zanubrutinib is a BTK inhibitor self-developed by BeiGene. Currently, it has been approved for multiple indications globally, including chronic lymphocytic leukemia (CLL), Waldenström's macroglobulinaemia (WM), mantle cell lymphoma (MCL), and marginal zone lymphoma (MZL). It is the BTK inhibitor with the most approved indications.

At the same time, Zanubrutinib has the potential to be best in its class, which stems from its unique design. In tests comparing it with Ibrutinib, the world's first BTK inhibitor approved for marketing, BeiGene found that the efficacy of BTK inhibitors depends on inhibiting BTK and has no relation to other targets. Additionally, it identified significant issues with adverse reactions and first-pass metabolism in Ibrutinib. In response, BeiGene decided to optimize selectivity and absorption to improve product quality. Ultimately, Zanubrutinib became the only BTK inhibitor to demonstrate superiority compared to Ibrutinib in head-to-head tests. It is currently approved in over 70 markets, including the United States, China, the EU, the United Kingdom, Canada, Australia, South Korea and Switzerland.

The potent efficacy helps Zanubrutinib to increase sales rapidly. In 2023, the sales volume of Zanubrutinib surpassed the USD billion mark for the first time, reaching USD 1.3 billion, making it the first "blockbuster drug" in China. In the first half of 2024, the sales volume reached new highs, with USD 489 million in Q1 and USD 637 million in Q2, with a year-on-year increase of 107%.

Fruquintinib

Fruquintinib is an orally administered multi-target VEGFR inhibitor developed by Hutchmed, which highly selectively inhibits VEGFR1-3. VEGFR inhibitors are pivotal in inhibiting tumor angiogenesis. Fruquintinib is designed with higher kinase selectivity to reduce off-target kinase activity, achieving higher drug exposure, sustained target coverage, and greater flexibility when potentially used as a combination therapy.

In March 2023, Takeda and Hutchmed reached an exclusive licensing agreement to further advance the development, commercialization, and production of fruquintinib globally, excluding Chinese Mainland, Hong Kong, and Macao. In November 2023, fruquintinib successfully obtained approval from FDA for marketing, becoming the first and only highly selective inhibitor targeting all three VEGF receptor kinases approved in the United States for the treatment of previously treated metastatic colorectal cancer (mCRC).

It is worth mentioning that within 48 hours of its launch in the United States, a doctor prescribed the first prescription of fruquintinib, and within a week, NCCN guidelines in the United States were updated to include fruquintinib as a clinical treatment option for third-line therapy in colorectal cancer. In June 2024, fruquintinib was approved by the EU for the treatment of previously treated mCRC. Fruquintinib is the first novel targeted therapy for mCRC approved in the EU in over a decade, regardless of the patient's biomarker status. Currently, Takeda Pharmaceutical is preparing for the commercial launch of the drug in the EU.

Since its launch in the United States market in November 2023, fruquintinib has exhibited strong commercial viability. In the first half of this year, fruquintinib achieved the sales volume of USD 61 million in Chinese market and USD 131 million in the United States market, totaling USD 192 million in sales volume over six months, indicating that the drug has the potential to become the next "blockbuster drug" with sales volume exceeding USD 1 billion.

Sunvozertinib

Sunvozertinib is an orally administered, potent, irreversible, and selective EGFR tyrosine kinase inhibitor (EGFR-TKI) developed by Dize Pharmaceuticals, marking the company's first original innovative product in its product pipeline. It has been approved in China for the second-line and above treatment of patients with EGFR exon20ins (EGFR exon 20 insertion mutation) non-small cell lung cancer (NSCLC).

EGFR is the most common mutation in NSCLC. Due to its unique spatial structure, EGFR exon20ins differs from EGFR sensitive mutations. Traditional first- to third-generation EGFR-TKIs, immunotherapy, and chemotherapy have objective response rates (ORR) of less than 20% for EGFR exon20ins. Moreover, patients with EGFR exon20ins NSCLC often have shorter survival times and poorer prognoses, with a long-standing lack of standard treatment.

Furthermore, the R&D of drugs targeting NSCLC EGFR exon20ins is highly challenging. Currently, only three targeted drugs have been approved for marketing: Johnson & Johnson's Amivantamab, Takeda's Mobocertinib, and Sunvozertinib. Notably, Mobocertinib was withdrawn from the market in 2023.

Dize Pharmaceuticals' Sunvozertinib has demonstrated significant efficacy. At ESMO Congress 2023, Sunvozertinib as a first-line treatment for EGFR exon20ins NSCLC achieved a confirmed ORR of 78.6% in the overall population, with a target lesion reduction observed in 100% of patients. The mPFS was 12.4 months, showing great potential.

In its pivotal clinical research WU-KONG6, Sunvozertinib achieved an ORR of 61% in patients, with more than 90% of patients experiencing a reduction in target lesions after treatment with Sunvozertinib monotherapy. Due to its remarkable efficacy and safety, Sunvozertinib has become the first and only first-in-class in the field of lung cancer to receive both Chinese and the United States "Breakthrough Therapy" designations.

Given the large global patient population of NSCLC, even though EGFR exon20ins mutations account for only about 10% of NSCLC cases, it still represents a significant market. Moreover, with limited therapeutic drugs available in this field, the market prospects for Sunvozertinib are promising.

In the first three quarters of this year, Dize Pharmaceuticals generated revenues of RMB 338 million, with Sunvozertinib being the main contributor. Currently, Sunvozertinib has submitted a marketing application to FDA. Once approved, it is expected to become the next "Billion Dollar Molecule" made in China.

Apart from the above three products, the CAR-T product Cilta-cel developed by LEGN.US in China has achieved remarkable sales since its FDA approval in late 2022. In 2022, the sales volume reached USD 134 million; in 2023, the sales volume were USD 500 million, with a year-on-year increase of 273%. Perhaps, Cilta-cel will become the second "Billion Dollar Molecule" made in China after Zanubrutinib.

After comprehensive analysis, we find that the rapid volume growth of pharmaceuticals is closely related to successful going global. This necessitates that the product possess robust clinical efficacy and safety, as well as differentiated advantages and a rapidly expanding range of indications. Meanwhile, collaboration with major pharmaceutical companies is also crucial, serving as a key pathway for local pharmaceutical companies to successfully internationalize at this stage. In the future, there will be more "Billion Dollar Molecules" made in China emerging.

Primary References:

1、BeiGene Enters Next Phase of Global Growth with Announcement of Second Quarter 2024 Financial Results and Corporate Updates. Businesswire.

2、https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/217003s000lbl.pdf.

3、Takeda Receives Positive CHMP Opinion for Fruquintinib in Previously Treated Metastatic Colorectal Cancer. Retrieved May 17, 2024, from https://www.takeda.com/newsroom/newsreleases/2024/positive-chmp-opinion-for-fruquintinib/.

About the author

Xiaobin

Xiaobin holds a Master's degree in Pharmacy and currently work as a public health control staff. Navigating through the intricate and complex data each day and feeling a sense of insignificance of herself. While being happy to witness the golden time of the development of Chinese bio-pharmaceutical industry. Hope to learn and improve together with everyone.