China NMPA accepts NDA for Innovent and HUTCHMED’s sintilimab-fruquintinib combo in advanced renal cell carcinoma

Why did Innovent Biologics (HKEX: 01801) and HUTCHMED (NASDAQ: HCM) file an NDA for Sintilimab-Fruquintinib in China?

Innovent Biologics Inc. (HKEX: 01801) and HUTCHMED (China) Limited (NASDAQ: HCM; AIM: HCM; HKEX: 13) jointly confirmed on June 4, 2025, that China’s National Medical Products Administration (NMPA) has formally accepted their New Drug Application (NDA) for a novel combination therapy involving sintilimab and fruquintinib. This treatment targets patients with locally advanced or metastatic renal cell carcinoma (RCC) who have previously failed tyrosine kinase inhibitor (TKI) therapy.

This regulatory acceptance is emblematic of China’s broader strategic pivot toward homegrown biopharma innovation, especially in oncology. The development reflects China’s intent to reduce reliance on imported treatments and instead focus on locally developed drugs that can offer comparable or superior efficacy at lower cost. With increasing incidence rates for RCC and mounting pressure on health infrastructure, this combination could offer much-needed clinical relief and market momentum.

How Did the FRUSICA-2 Study Enable NDA Progress for the Sintilimab-Fruquintinib Combo?

The NDA was primarily driven by the FRUSICA-2 study, a randomized, open-label, active-controlled Phase 3 trial registered under ClinicalTrials.gov identifier NCT05522231. The study evaluated the efficacy of sintilimab and fruquintinib against monotherapy comparators axitinib and everolimus in patients with advanced RCC following failure of first-line therapy. The combination successfully met its primary endpoint of progression-free survival (PFS), with assessments performed by blinded independent central review using RECIST 1.1 criteria. Secondary endpoints such as objective response rate (ORR) and duration of response (DoR) were also favorably impacted, strengthening the submission’s clinical foundation.

Of equal importance, the safety profile of the combination was found to be tolerable, with no new or unexpected adverse events reported. This finding is crucial in a therapeutic area where patients are often immunocompromised and treatment-experienced. The data package is now poised for peer-reviewed presentation at an upcoming global oncology congress, where it is expected to reinforce China’s growing role as a clinical innovator in immuno-oncology.

What is the Significance of This Approval in the Context of China’s Kidney Cancer Burden?

In 2022, China recorded approximately 74,000 new cases of kidney cancer, of which over 90% were renal cell carcinoma. With improved diagnostic capabilities and greater awareness, RCC diagnoses are projected to increase in the coming years. Despite the growing need, second-line treatment options have remained limited and heavily reliant on older agents with modest efficacy and poor tolerability.

The sintilimab-fruquintinib combination directly addresses this therapeutic void. It introduces a new immuno-vascular strategy designed to overcome resistance pathways and improve clinical outcomes. In the context of an aging population and rising cancer burden, particularly in Tier 2 and Tier 3 cities, the therapy is likely to deliver significant healthcare value. It is expected to be cost-effective and easier to integrate into existing treatment frameworks due to its domestic origin and probable inclusion in China’s National Reimbursement Drug List (NRDL).

What is the Mechanism of Action for Sintilimab and Fruquintinib?

Sintilimab, marketed as TYVYT in China, is a PD-1 monoclonal antibody that binds to PD-1 receptors on T cells. By blocking the PD-1/PD-L1 interaction, it reactivates the body’s immune response, enabling cytotoxic T cells to recognize and destroy tumor cells. The drug is co-developed by Innovent and Eli Lilly and has received regulatory approval for multiple indications, including non-small cell lung cancer (NSCLC), esophageal squamous cell carcinoma, hepatocellular carcinoma, and more.

Fruquintinib is an oral, small-molecule inhibitor of vascular endothelial growth factor receptors (VEGFR-1, VEGFR-2, and VEGFR-3). It disrupts the blood supply to tumors, effectively starving them of the nutrients and oxygen needed for growth and survival. When combined, these two mechanisms—immune checkpoint inhibition and anti-angiogenesis—create a potent synergy that enhances both the immune response and limits tumor progression.

What is the Commercial Landscape for RCC Treatments in China?

The Chinese market for RCC therapies has historically been dominated by first-generation TKIs like sunitinib and imported PD-1 inhibitors such as nivolumab and pembrolizumab. However, high costs and restricted access have limited their reach, particularly outside major metropolitan areas. Innovent and HUTCHMED’s sintilimab-fruquintinib combination is uniquely positioned to change this dynamic by offering a domestically developed, more affordable treatment with proven clinical efficacy.

With sintilimab already included in the NRDL for multiple indications, and fruquintinib’s growing profile in the gastrointestinal and endometrial cancer segments, the combination is likely to enjoy rapid uptake following formal approval. Analysts expect strong penetration in both public and private healthcare institutions, and favorable positioning in provincial reimbursement lists.

How Has the Sintilimab-Fruquintinib Combo Fared in Other Indications?

In December 2024, the NMPA granted conditional approval for the combination’s use in advanced mismatch repair proficient (pMMR) endometrial cancer. That decision was based on results from the FRUSICA-1 study (NCT03903705), which demonstrated strong efficacy and a manageable safety profile. This success has reinforced confidence in the combination’s applicability across multiple solid tumor types.

The move from endometrial cancer to RCC represents a natural progression in label expansion. Both conditions involve tumor microenvironments that can be influenced by VEGFR and PD-1 activity, making them ideal targets for this combination. Further clinical programs exploring colorectal, hepatobiliary, and gastric cancers are also underway, suggesting that the NDA acceptance for RCC is merely the beginning of a broader strategic rollout.

What Are the Financial and Strategic Implications for Innovent Biologics?

Innovent Biologics reported RMB 6.2 billion in annual revenues for FY2024, with TYVYT alone contributing more than 50% of the oncology portfolio’s earnings. Gross margins reached 74.6%, buoyed by the company’s vertically integrated manufacturing platform and expanding hospital coverage. The acceptance of this NDA is expected to add RMB 1.5 to 2 billion in incremental revenues over the next three years, contingent on pricing and NRDL inclusion.

Strategically, this development helps Innovent fortify TYVYT’s lifecycle, positioning it as a platform product rather than a single-indication therapy. With multiple ongoing trials and NDA submissions—including one in combination with ipilimumab for colon cancer—Innovent’s leadership in domestic immuno-oncology remains unmatched.

How Does HUTCHMED Stand to Gain from Regulatory Acceleration?

HUTCHMED’s revenues reached $535 million in 2024, with over $300 million reinvested into R&D, reflecting its commitment to oncology innovation. Fruquintinib, a flagship product, is central to the company’s strategy for solid tumors. The RCC NDA acceptance elevates fruquintinib’s market value and accelerates its commercialization timeline, offering potential licensing opportunities in ex-China markets.

Market analysts have responded favorably, with buy-side institutions increasing exposure to HUTCHMED following the FRUSICA-2 data release. Investment houses like Jefferies and Citibank maintain “Overweight” ratings on HUTCHMED stock, citing robust pipeline visibility and commercial execution.

How Has the Market Reacted to This Development?

In the 24 hours post-announcement, Innovent Biologics’ shares on the HKEX rose by 3.7%, with daily trading volume doubling. HUTCHMED experienced a 4.1% surge in U.S. pre-market trading, reflecting positive sentiment among biotech-focused institutional investors. Derivative trading around both tickers also intensified, with call options significantly outweighing puts—an indicator of short-term bullish sentiment.

Flow data from investment platforms show net buying from domestic and offshore funds, particularly those specializing in Asia-Pacific healthcare and growth biotech portfolios. While some investors await pricing clarity, the overall reaction indicates confidence in regulatory approval and commercial potential.

What Lies Ahead for the Sintilimab-Fruquintinib Combination?

The current NDA represents a significant regulatory milestone, but the trajectory for this combination points toward broader geographic and clinical expansion. Trials are underway to explore its role in colorectal, gastric, and hepatobiliary cancers. Furthermore, analysts believe the duo could be among the first Chinese-developed combination regimens to receive recognition or licensing in global emerging markets, particularly in Southeast Asia and Latin America.

M&A speculation has also intensified, with the combination’s success making both Innovent and HUTCHMED attractive partners or targets for international pharmaceutical firms seeking entry into the Chinese market. Strategic partnerships, regional licensing deals, or even dual-market filings in the U.S. and EU are all within the realm of possibility over the next 12 to 18 months.

What Are the Analyst Expectations and Future Risks?

Despite the encouraging signals, analysts caution that commercial execution will depend heavily on NRDL inclusion and competitive pricing relative to entrenched global brands. Reimbursement mechanisms and local hospital procurement systems will play a decisive role in uptake. Additionally, while the trial data is promising, real-world performance and post-marketing surveillance will ultimately determine long-term success.

Nonetheless, the momentum is clearly with Innovent Biologics and HUTCHMED. The regulatory acceptance of the sintilimab-fruquintinib combination for advanced RCC reinforces both companies’ status as pioneers in China’s biopharma transformation. With a growing portfolio, expanding clinical footprint, and investor backing, they are well-poised to define the next chapter of domestic oncology innovation.