Made-in-China New Drugs: Breaking Through the RMB 4-Billion Battlefield

Preface

In 2024, the "Billion-Yuan Club" of made-in-China first-in-class new drugs expanded to 16 members. Yet beneath the spotlight lies hidden turbulence. Tislelizumab reached RMB 4.4 billion but its growth slowed to 17.4%; Almonertinib, with RMB 4 billion in sales, held its ground atop the EGFR category; Candonilimab, as the world's first PD-1/CTLA-4 bispecific antibody, broke through with RMB 1.5 billion. As PD-1s plunge into fierce competition and third-generation EGFR inhibitors face pressure from fourth-generation challengers, the non-tumor "dark horse" Tegoprazan Tablets surged with 475% growth. This article looks beyond sales volume to analyze four core battlegrounds - clinical positioning, reimbursement negotiations, indication expansion, and technology iteration - to uncover how Billion-Yuan blockbusters survive.

I. "Fire and Ice" of PD-1

In the biological medicine field, competition in the PD-1 inhibitor market is intense. Numerous pharmaceutical companies have entered, aiming to seize a share of this promising segment. In this fierce contest, Tislelizumab from BeiGene and Sintilimab from Innovent have shown sharply different development trajectories.

Reality Behind Divergent Growth Rates

Tislelizumab from BeiGene achieved sales volume of RMB 4.467 billion in 2024, with a year-on-year increase of 17.4%. This performance largely benefited from support from overseas markets. BeiGene's Zanubrutinib generated RMB 18.859 billion in sales volume in 2024, providing strong financial backing for the R&D of Tislelizumab. In Chinese market, Tislelizumab primarily holds its ground in major indications such as gastric and liver cancers. Take gastric cancer treatment as an example: Tislelizumab activates the patient's immune system through precise immunomodulation to combat tumor cells, offering new hope to many gastric cancer patients. In liver cancer therapy, it has also demonstrated certain efficacy advantages, effectively prolonging patient survival and improving quality of life.

In contrast, Innovent' Sintilimab showed weaker growth momentum. However, Innovent gained significant support through its partnership with Eli Lilly. The authorization fee for Sintilimab doubled to RMB 1.1 billion, providing a solid "going global cash flow" for Innovent that partially offsets Chinese market pressure caused by involution. Although Sintilimab faces fierce rivalry in Chinese market, Innovent's collaboration with an international pharmaceutical company enables expansion into overseas markets and pursuit of new growth opportunities. This partnership model offers a reference for other Chinese pharmaceutical companies - leveraging global cooperation to share resources, complement strengths, and enhance competitiveness on the world stage.

Exploring the Second Growth Curve

Hengrui Pharmaceuticals' Camrelizumab surpassed RMB 1.83 billion in sales volume in 2024, with its growth strategy focused primarily on the "PD-1 plus chemotherapy" combination regimen. Clinical research has demonstrated that this combined approach delivers synergistic effects across multiple cancer types. In lung cancer treatment, Camrelizumab used alongside chemotherapy drugs significantly improves patients' ORR and prolongs progression-free survival (PFS). The advantage of this combination lies in its dual mechanism: activating the immune system through PD-1 inhibitor while directly killing tumor cells via chemotherapy, resulting in enhanced therapeutic effect. Hengrui Pharmaceuticals continues to increase R&D investment in this area, actively conducting clinical trials to further refine the optimal combinations and timing for the regimen, aiming to provide patients with more effective treatment options.

After its launch at the end of 2023, Ivonescimab, a PD-1/VEGF bispecific antibody, rapidly became a focal point in the market, targeting the broad first-line treatment segment of lung cancer. It is one of the malignant tumors of morbidity and mortality rate worldwide, with huge market demand for first-line treatment. As a bispecific antibody, Ivonescimab has unique mechanism of action to block both PD-1 and VEGF signaling pathways, exerting stronger anti-tumor effects. Clinical trials have shown promising efficacy and safety, offering new hope to lung cancer patients. Akeso is actively advancing the commercialization of Ivonescimab, strengthening marketing efforts and improving accessibility, striving to secure a foothold in the first-line treatment market of lung cancer.

II. Technological Leapfrogging: "4-billion Legend" of Almonertinib and Challenge of Fourth-generation Drugs

In the lung cancer targeted therapy field, Hansoh Pharma's Almonertinib mesylate tablets have written an impressive "4-billion legend". Since its market debut in 2020, Almonertinib rapidly gained traction and by 2024, surpassed RMB 4 billion in sales volume, emerging as the leading made-in-China third-generation EGFR inhibitor and drawing intense industry focus on the third-generation EGFR market.

Dominance of Third-generation EGFR Inhibitors

The remarkable success of Almonertinib can largely be attributed to its notable advantage in treating brain metastases. Compared with Osimertinib, another third-generation EGFR inhibitor, Almonertinib features a distinct design - specifically, a fluorine-substituted hydrogen structure that blocks metabolic sites. This innovative approach reduces the formation of certain metabolites responsible for side effects such as diarrhea, thereby improving patient tolerability during treatment. In patients with brain metastases, Almonertinib has demonstrated outstanding performance. It more readily penetrates the blood-brain barrier, achieving higher drug concentrations in brain tissue and exerting stronger inhibitory effects on brain metastases lesions. According to a subgroup analysis from the 2023 AENEAS study, Almonertinib achieved a median PFS of 19.3 months in Chinese patients with brain metastases receiving first-line treatment, compared with 18.9 months for Osimertinib. This data suggests that Almonertinib holds a modest but meaningful advantage in prolonging PFS for patients with brain metastases, offering renewed hope for this challenging patient population.

In 2020, Almonertinib was successfully included in China's National Reimbursement Drug List (NRDL), with a reimbursement price set at RMB 176 per 55mg tablet - a price cut of 64%. Typically, such a substantial reduction following inclusion in the NRDL could dampen sales volume. However, Almonertinib defied this trend. Post-reimbursement, the drug's accessibility improved significantly, enabling more patients to afford treatment. This rapid increase in affordability unlocked previously restrained market demand. More physicians became willing to recommend Almonertinib to suitable patients, while patients, supported by insurance coverage, were more inclined to initiate therapy. This case highlights a critical insight in the pharmaceutical market: for drugs targeting essential, high-demand indications with proven clinical superiority, price reductions do not necessarily weaken market performance. Instead, such drugs demonstrate strong and sustained demand due to their irreplaceability. Backed by solid efficacy and favorable reimbursement policy, Almonertinib has secured a firm position in lung cancer therapy field, becoming one of the top choices among both physicians and patients.

Siege and Counterattack of Fourth-generation Drugs

As the third-generation EGFR inhibitor market gradually matures, the R&D of fourth-generation EGFR inhibitors is intensifying, quietly ushering in a fierce market competition. Zai Lab's BLU-945, licensed from Blueprint, has emerged as a strong potential challenger to Almonertinib. BLU-945 is an oral fourth-generation EGFR inhibitor under development that selectively targets L858R, C797X single mutations, or T790M/C797X double mutations - key mutations responsible for resistance to third-generation EGFR inhibitors. Currently, BLU-945 is in Phase III clinical research in China, and if successfully R&D and launched, it will pose a significant threat to Almonertinib's resistance market. For patients who develop resistance after Almonertinib treatment, BLU-945 could become a new therapeutic option, inevitably drawing away part of Almonertinib's market share.

In response to the pressure from fourth-generation drugs, Hansoh Pharma swiftly accelerated clinical trials of HS-10382, its self-developed fourth-generation EGFR inhibitor. HS-10382 aims to address treatment challenges following resistance to third-generation EGFR inhibitors. By advancing clinical trial, Hansoh Pharma hopes to verify HS-10382's safety and efficacy, offering patients additional treatment choices. This strategy of self-iteration is Hansoh Pharma's crucial defensive tactic to counter competitors and maintain market competitiveness. Through continuous R&D of next-generation drugs, Hansoh Pharma can meet patient needs at various treatment stages, consolidating its position in lung cancer targeted therapy field. Even if BLU-945 successfully enters the market, Hansoh Pharma's own fourth-generation product will compete effectively, preventing it from falling into a passive position in market battles.

III. Bispecific Antibody Breakthrough: Candonilimab's Rapid Expansion of Indications

In the field of tumor immunotherapy, bispecific antibody drugs are emerging as a powerful new force. Among them, Akeso's Candonilimab has stood out with remarkable performance, achieving cumulative sales volume exceeding RMB 3 billion in just three years. Candonilimab has successfully disrupted the traditional PD-1 inhibitor market landscape, opening a new chapter in tumor immunotherapy.

From Cervical Cancer to Gastric Cancer: Deepening the Indication Breakthrough

In 2022, Candonilimab was approved for second-line treatment of recurrent or metastatic cervical cancer, filling a significant gap in the immunotherapy options for this disease. Shortly after approval, Candonilimab demonstrated strong market potential, generating RMB 300 million in sales volume within the first year. Its success is attributed to precise market positioning and outstanding clinical efficacy. Previously, treatment options for cervical cancer therapy field were limited, and patients had an urgent need for new therapies. As the world's first approved for marketing bispecific antibody for tumor immunotherapy, Candonilimab brought new hope to patients with recurrent or metastatic cervical cancer. In clinical trials, it showed good safety and efficacy profiles, significantly improving ORR and extending patient survival.

In 2023, Candonilimab made another breakthrough by securing approval for first-line treatment indication of gastric cancer. This breakthrough propelled Candonilimab's sales volume to soar, reaching RMB 1.2 billion that year. Gastric cancer is one of the most common malignant tumors worldwide, with China accounting for nearly half of the new cases and deaths globally. In gastric cancer therapy field, patients with low or negative PD-L1 expression have long faced therapeutic challenges, as existing treatments offer limited benefits for this group. The emergence of Candonilimab has brought new hope to these patients. Based on the COMPASSION-15 study, Candonilimab combined with fluoropyrimidine- and platinum-based chemotherapy demonstrated significant efficacy across the entire advanced gastric cancer patient population. Notably, in patients with PD-L1 CPS < 5 and PD-L1 CPS < 1, the risk of death was substantially reduced, and overall survival was significantly prolonged. In the intent-to-treat (ITT) population, the Candonilimab regimen achieved a median overall survival (mOS) of 15.0 months, extending patient survival by 4.2 months compared with 10.8 months in the control group. This corresponded to a 38% reduction in the risk of death (HR=0.62) versus the control group. In the PD-L1 CPS < 5 group, the Candonilimab regimen achieved the mOS of 14.8 months, representing a 30% reduction in the risk of death compared with the control group, which had the mOS of 11.1 months (HR=0.70). These data fully demonstrate Candonilimab's advantages in first-line treatment of gastric cancer and have laid a solid foundation for its market expansion.

By 2024, Candonilimab's sales volume continued to climb, reaching RMB 1.5 billion. Its successful clinical strategy lies in prioritizing cancers with no established standard treatments, skillfully avoiding the fierce competition within PD-1. When selecting indications, Akeso precisely targeted unmet clinical needs such as PD-L1 negative gastric cancer. Through conducting large-scale clinical trial, Candonilimab demonstrated unique efficacy in these cancer types, quickly gaining market recognition. This differentiated competitive strategy allowed Candonilimab to stand out in the fierce market competition, becoming a shining star in the field of tumor immunotherapy.

A Powerful Engine for Future Growth

Candonilimab's Phase III clinical data in NSCLC field are expected soon, injecting strong momentum into its future growth. Lung cancer is one of the malignant tumors with the highest morbidity and mortality rate worldwide, with NSCLC accounting for 80%-85% of cases, representing a vast market potential. Currently, Candonilimab shows promising prospects in NSCLC clinical trials and has the potential to become a new treatment option for lung cancer. Once the clinical trials succeed, Candonilimab will directly compete with Keytruda (Pembrolizumab) and Opdivo (Nivolumab), two internationally renowned PD-1 inhibitors with significant market share and strong reputations in lung cancer therapy field. However, Candonilimab's unique bispecific antibody mechanism, simultaneously blocking PD-1 and CTLA-4 pathways, offers stronger anti-tumor effects and may help it stand out in this competition, providing patients with a more effective treatment option.

Candonilimab holds significant advantages from a pharmacoeconomic perspective. Compared with traditional combination therapy, Candonilimab is used as a single-drug with lower overall costs. The treatment regimen mentioned in the attachment - "five injections per year" - greatly reduces both the treatment expenses and medication burden for patients. In conventional combination therapy, patients often need multiple drugs simultaneously, which not only raises treatment expenses but also increases the risk of adverse reactions. Candonilimab's monotherapy simplifies the treatment process, lowers treatment expenses, and improves patient adherence. This cost advantage enhances Candonilimab's competitiveness in the market and is poised to reshape the pharmacoeconomic logic of tumor immunotherapy, offering more affordable treatment options to a broader patient population.

IV. Non-tumor "Dark Horse": "Track Hijacking" Logic Behind Tegoprazan's 475% Growth

In a biopharmaceutical market dominated by antitumor drug, non-tumor new drugs have emerged like a dark horse. Leveraging unique advantages and rapid growth momentum, they have carved out their own space in the market, becoming an influential force within the industry. Their success is no accident - it reflects deep market insight and innovative R&D strategies, prompting a deeper reflection on the evolving trends in the pharmaceutical market.

A Breakthrough Model in the Digestive/Metabolic Field

Tegoprazan Tablets from Shandong Luoxin, a potassium-competitive acid blocker (P-CAB), have demonstrated outstanding efficacy in treating digestive system diseases such as gastroesophageal reflux disease (GERD). Thanks to its unique mechanism of action, Tegoprazan does not require acid activation and can rapidly exert acid suppression, maintaining strong acid control for 24 hours continuously. In GERD reatment, Tegoprazan Tablets can quickly alleviate typical symptoms like heartburn and acid regurgitation. Clinical research shows that patients experience a significantly higher relief rate of heartburn symptoms on the first day of taking Tegoprazan Tablets compared with traditional PPIs. Furthermore, early treatment phases (1-2 weeks) see faster relief of pain and other symptoms, significantly improving patients' quality of life. The arrival of Tegoprazan Tablets has brought new hope to patients suffering from GERD and injected fresh vitality into the digestive drugs market. Its sales volume growth rate reached an impressive 475% in 2024, making it a star product in the digestive field. This achievement fully reflects its strong market competitiveness and high patient acceptance.

Hua Medicine's Dorzagliatin Tablets represent an innovative breakthrough in diabetes therapy field. As the world's first glucose kinase activator (GKA), it overcomes the limitations of traditional diabetes therapeutic drugs and opens a new chapter in diabetes therapy. Dorzagliatin Tablets work by restoring the impaired function of glucokinase (GK), thereby reshaping blood glucose homeostasis and offering a novel therapeutic approach for diabetic patients. Clinical trials have demonstrated that Dorzagliatin Tablets are both safe and effective, which can not only significantly lower blood glucose levels but also improve early-phase insulin secretion, reduce insulin resistance, and help control and delay the progression of T2D. Notably, Dorzagliatin Tablets are particularly well-tolerated by diabetic patients with renal impairment, requiring no dosage adjustment, which greatly enhances convenience for a wide patient population. Currently, Dorzagliatin Tablets boast annual sales exceeding 100 million units and continue to grow, indicating a very promising market outlook. With the increasing demand for diabetes treatments and rising awareness of Dorzagliatin Tablets, it is expected that they can play an increasingly important role in diabetes therapy field.

Hansoh Pharma's Tenofovir Amibufenamide Tablets stand out as a leading treatment in the therapy field of hepatitis B. Leveraging the convenience of oral administration, it has successfully replaced traditional oral nucleoside drugs, offering hepatitis B patients a more accessible treatment option. Tenofovir Amibufenamide Tablets work by inhibiting the reverse transcriptase activity of the hepatitis B virus (HBV), effectively suppressing viral replication and reducing viral load. Clinical trials have shown that Tenofovir Amibufenamide Tablets deliver significant therapeutic benefits for treatment-naive chronic hepatitis B patients, effectively inhibiting viral replication and improving liver function, all while maintaining a favorable safety profile. Compared with conventional injectable interferons, the oral dosage of Tenofovir Amibufenamide Tablets greatly enhances patient adherence, eliminating the need for frequent hospital visits for injections and enabling patients to complete treatment conveniently at home. This advantage has led to the rapid market acceptance of Tenofovir Amibufenamide Tablets, with sales volume surpassing RMB 800 million within just three years. Its success also offers valuable insights for the R&D and promotion of other hepatitis B therapeutic drugs, highlighting that prioritizing drug convenience and patient experience better meets patients' needs.

Insights and Reflections on Breaking Through

The success of these non-tumor new drugs offers valuable insights into key strategies for breaking through in the fiercely competitive pharmaceutical market. To avoid the intense involution in the tumor field, attention should be focused on fields with large patient populations and challenges in medication adherence. Diseases such as diabetes and GERD have large patient bases and urgent treatment needs. Traditional therapies often come with shortcomings that cause inconvenience for patients. Therefore, focusing R&D efforts on these fields can better meet patient needs and increase the likelihood of market success. Shandong Luoxin's Tegoprazan Tablets address the shortcomings of traditional PPIs in treating GERD, such as poor therapeutic effect and slow symptom relief; Hua Medicine's Dorzagliatin Tablets target diabetic patients and overcome the limitations of conventional antidiabetic drugs, offering a more effective treatment option.

Efforts are made to create strong market barriers through dosage innovation or first-in-class mechanisms. Shandong Luoxin's Tegoprazan Tablets use a P-CAB mechanism to achieve more efficient acid suppression; Hua Medicine's Dorzagliatin Tablets introduce a first-in-class glucokinase activation mechanism, addressing blood glucose regulation at its source for diabetic patients; Hansoh Pharma's Tenofovir Amibufenamide Tablets represent a dosage innovation by replacing injectable treatments with oral administration, significantly improving patient adherence. These innovations have allowed the products to stand out and become first choices among patients and physicians. For pharmaceutical companies, only by continuously increasing R&D investment and embracing innovation can they remain competitive in the pharmaceutical market and bring better treatment options to patients.

Conclusions

The competition to join the "Billion-Yuan Club" has evolved from a simple race in sales volume to a three-dimensional battle involving the speed of indication expansion, generational technological advancements, and the ability to break through in non-tumor areas. "Tislelizumab's Going Global Feedback", "Candonilimab's Rapid Expansion of Indications", and "Tegoprazan's Dosage Revolution" signify three distinctly different survival philosophies. As the golden era of PD-1 comes to an end, the next generation of leaders will inevitably belong to those versatile players who can simultaneously master clinical value, medical insurance negotiations, and global business development. In this race of life and death, there is no endpoint, only increasingly ruthless elimination.