Hengrui Medicine Fills the Void Left by Merck and GSK with Global First-in-Class PD-L1/TGF-βRII Bispecific Fusion Protein

Jan 16, 2026 17:12 CST Updated 17:12

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Hengrui Pharma

Innovative and High-Quality Pharmaceutical Developer

Hengrui Pharma Launches a "Major Breakthrough".

On January 7, 2026, Hengrui Pharma announced that its subsidiary, Suzhou Shengdiya, had received notification from the National Medical Products Administration (NMPA) approving the market launch of its self-developed Class 1 innovative drug, Relafusp Alfa Injection.

This medication, in combination with fluorouracil and platinum-based drugs, is indicated for the first-line treatment of locally advanced unresectable, recurrent, or metastatic gastric and gastroesophageal junction adenocarcinoma that is PD-L1 positive (CPS≥1) as assessed by a fully validated test.

Relafusp Alfa Injection is a bifunctional fusion protein developed by Hengrui Pharma that targets PD-L1 and TGF-βRII. By specifically blocking the interaction between PD-1 and PD-L1, it can simultaneously neutralize TGF-β in the tumor microenvironment, exerting an anti-tumor effect.

To date, the total R&D investment in Relafusp Alpha Injection-related projects has amounted to approximately 711 million yuan.

So far, globally, no similar drug targeting this combination has been approved for marketing, and Hengrui Pharma has successfully taken the "first blood."

Not only that, but this combination of targets has also become a "heartbreak" for many leading multinational pharmaceutical companies, including Merck and GSK.

The wind started in 2018

The popularity of the PD-L1/TGF-β target began at the 2018 American Society of Clinical Oncology (ASCO) Annual Meeting.

At this year's ASCO conference, Merck published astonishing Phase I clinical data:

In the population of non-small cell lung cancer patients, when the dose was 500mg, the overall ORR was 22.6%, with an ORR of 33.3% in patients with high PD-L1 expression;

At a dose of 1200mg, the overall ORR reached an impressive 40.7%, while in patients with high PD-L1 expression, the ORR was as high as 71.4%!

For a time, Merck's M7824, a PD-L1/TGF-β bispecific antibody, seemed to have the momentum of a new king ascending the throne, becoming the focal point of the global pharmaceutical industry that year. It even boldly proclaimed itself as the "second-generation PD-1."

Excellent data quickly attracted partners.

On February 12, 2019, GSK and Merck announced that they had reached a global strategic alliance to jointly oversee the clinical development and commercial promotion of M7824 worldwide.

In this collaboration, Merck can receive an upfront payment of 300 million euros, a research and development milestone payment of 500 million euros from GSK, and a commercial sales milestone payment of 2.9 billion euros after the future product launch, with the total transaction amounting to up to 3.7 billion euros.

Failure, again failure!

Time quickly moved to 2021, and the development situation of this highly anticipated star molecule took a sharp downturn.

On January 15, 2021, M7824 in the treatment of patients who had disease progression after receiving immune checkpoint inhibitors (ICB)In the phase II study of patients with high microsatellite instability (MSI-H)/mismatch repair deficiency (dMMR) solid tumors,No antitumor activity was observed, the trial ultimately ended in failure.

On January 20, 2021, Merck announced the terminationM7824The phase III clinical trial of lung cancer. According to the analysis,Independent Data Monitoring CommitteeIt is believed that the ongoing Phase III clinical trials for non-small cell lung cancer,Unlikely to beat Keytruda (commonly known as K drug) in reaching the primary efficacy endpoint, the company has decided to terminate the clinical trial.

On March 16, 2021, Merck announced the failure of the Phase II clinical trial BTC-047 for M7824 in biliary tract cancer.

On August 23, 2021, Merck announced again that another ongoing clinical trial of M7824 for bile duct cancer treatment, BTC-055, had failed to meet its expected goals.

The successive failures made GSK consider withdrawing.

On September 30, 2021, Merck announced an agreement with GSK to terminate the collaboration on M7824, effective as of September 30, 2021.

Thus far,The development of the PD-L1/TGF-β target combination has hit a low globally.Tide.

If the west doesn't shine, the east will.

As the world's first successfully approved and marketed PD-L1/TGF-β dual-target drug, Hengrui Pharma's Relafusp-alpha Injection has broken the doubts about the target being "undruggable" or under an "efficacy curse."

The core evidence supporting the drug's approval comes from a multicenter, randomized, double-blind Phase III clinical trial, the data of which was released as a late-breaking abstract (LBA) at the 2024 European Society for Medical Oncology (ESMO) Annual Meeting.

In the intent-to-treat population (ITT), the median overall survival (mOS) in the SHR-1701 combination group reached 15.8 months, significantly extending by 4.6 months compared to 11.2 months in the placebo plus chemotherapy group, substantially reducing the risk of patient mortality. Meanwhile, the median progression-free survival (mPFS) increased from 5.5 months in the control group to 7.0 months, and the objective response rate (ORR) was as high as 53.4%, markedly superior to 32.8% in the chemotherapy-alone group.

From the changes in the clinical trials published by Hengrui Pharma, the development process of this pipeline has also been quite曲折.

In the 2022 annual report, Hengrui Pharma disclosedMultiple Clinical Trials of Relafup α Injection (SHR-1701)。

However, in the 2024 annual report, the disclosed clinical trials for SHR-1701, aside from one that has already submitted an NDA (which is the indication approved this time), only a lone Phase I clinical trial in Australia remains.

After successfully securing the first indication,Relafusp Alpha Injection as GlobalThe sole target of PD-L1/TGF-β, whether it can reach a BD cooperation with multinational pharmaceutical companies, is an important future highlight.

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