Hengrui's ADC breaks into the first-line treatment for breast cancer: positive PFS result, how far is it from reshaping the treatment landscape?
Thus obtaining the key bargaining chip to compete for the HER2-positive first-line treatment market
On August 31, Hengrui Medicine (600276.SH / 01276.HK) announced that the key Phase III SHR-A1811-307 study of its independently developed HER2-targeted antibody-drug conjugate (ADC) Trastuzumab Rcanmisine (SHR-A1811) by its subsidiary Suzhou Shengdiya for first-line treatment of HER2-positive recurrent or metastatic breast cancer has reached the preset primary endpoint of progression-free survival (PFS) in the interim analysis.
Moving from later-line treatment to first-line treatment is a key step for this domestic ADC to realize value escalation. However, the overall survival (OS) data of this drug is not yet mature at present, and how to choose between the two trial regimens and what the long-term safety performance will be still need further verification with complete data.
Clinical Success Carries Dual Significance
The results show that compared with the standard THP (docetaxel, trastuzumab combined with pertuzumab) regimen, trastuzumab rcanmisine with or without pertuzumab can significantly prolong the progression-free survival of patients, with statistical and clinical significance.
This study is led by Professor Jiang Zefei and Professor Yin Yongmei, with the participation of 75 clinical centers across the country, and a total of 868 subjects were enrolled. The company will recently submit a pre-marketing communication application to the Center for Drug Evaluation (CDE) of the National Medical Products Administration to promote the registration and declaration of the first-line indication.
For more than ten years, THP has always been the mainstream standard regimen for first-line treatment of HER2-positive advanced breast cancer. This regimen achieves disease control through chemotherapy combined with dual targeting, but problems such as myelosuppression and gastrointestinal adverse reactions caused by chemotherapy may continuously affect the quality of life of patients.
This Phase III study adopts a two-arm design, and evaluates the two paths of trastuzumab rcanmisine combined with pertuzumab and monotherapy at the same time. Among them, the regimen without pertuzumab is particularly noteworthy. If finally supported by complete data, this regimen is expected to reduce combined medication, lower the treatment burden, and provide new treatment options for clinical practice.
It should be noted that at present, the company has only announced the PFS interim analysis results, the OS data is not yet mature, and the complete safety data remains to be disclosed. This indication still needs to go through the full registration and review process before the official submission of the marketing application and approval for launch.
Advancing from Later-Line to First-Line for Commercial Value Upgrading
Trastuzumab rcanmisine is a new generation of HER2-targeted ADC independently developed by Hengrui Medicine, with a drug-to-antibody ratio (DAR) of 6. It can bind to HER2-expressing tumor cells and be internalized, release toxins through protease cleavage in the lysosome of tumor cells, induce cell cycle arrest and thus induce tumor cell apoptosis. At present, this drug has carried out clinical studies in multiple tumor types and treatment lines such as lung cancer, breast cancer, and colorectal cancer, showing broad therapeutic potential.
Previously, the value verification of trastuzumab rcanmisine was mainly focused on later-line treatment. The later-line market mostly meets the clinical needs after the failure of standard regimen treatment. Once the first-line indication is approved, this drug will have the opportunity to enter the priority treatment sequence for newly treated patients, and the potential market space is expected to expand significantly.
Referring to the path of trastuzumab deruxtecan (DS-8201) promoting the paradigm shift of global HER2-positive breast cancer treatment, the first-line breakthrough is an important inflection point for domestic ADCs to enhance clinical and commercial value.
Looking at the domestic HER2 ADC track, a number of products have been approved for marketing, and imported products and local innovative drugs are competing on the same stage. In the field of breast cancer, the focus of industry competition has gradually shifted from later-line treatment to the first-line position. Globally, ADCs continue to change the treatment paradigm of HER2-positive tumors, and reducing chemotherapy and combined medication has also become an important clinical exploration direction.
This time, trastuzumab rcanmisine adopts a two-arm design, directly compares with the traditional THP gold standard, and tries to answer the core clinical question of "whether ADC can replace traditional chemotherapy combined with dual targeted therapy". If the final data is sufficient, it is not only expected to provide the clinic with a new option that balances efficacy and safety, but also may promote domestic ADCs to move from follow-on innovation to a new stage of participating in defining the first-line treatment standard.
From the company's perspective, trastuzumab rcanmisine is one of the core assets in Hengrui Medicine's innovative drug pipeline, covering multiple major tumor types such as lung cancer, breast cancer, and colorectal cancer, and a number of Phase III clinical studies are underway. If the first-line breast cancer indication advances smoothly and is approved, it will further expand the commercial space of this product and is expected to become an important growth source for the company's innovative drug sector.
PFS Is Only the Admission Ticket, Multiple Challenges Remain
The positive PFS result obtained in the Phase III interim analysis means that trastuzumab rcanmisine has taken a key step towards first-line treatment, but the realization of its clinical and commercial value still needs to cross multiple hurdles.
First of all, overall survival (OS) is an important indicator for evaluating the long-term benefit of advanced tumor drugs. At present, the OS data of this study is not yet mature, and whether the PFS benefit can be further transformed into the overall survival benefit of patients still needs to be verified by subsequent follow-up results. Which of the two trial regimens has a better benefit-risk ratio also needs to be judged in combination with the complete data set.
Secondly, in terms of safety, ADCs usually need to focus on special adverse reactions such as interstitial lung disease. The long-term safety performance of trastuzumab rcanmisine in the large sample of first-line treatment population remains to be continuously observed. Reducing combined medication does not necessarily mean lower toxicity, and the conclusion ultimately needs to be supported by data such as adverse reaction incidence rate, drug withdrawal rate and patient quality of life.
In terms of commercialization, even if the indication is approved smoothly, the product will still face fierce competition. Imported ADCs already have first-mover advantages, and factors such as medical insurance access, hospital access, physician awareness education and patient affordability will all affect the penetration rate of the product in the real world. At the same time, other domestic ADCs targeting the same target are also continuously advancing clinical R&D, and the future market competition may further intensify.
From the perspective of the industry, the R&D of the ADC track is highly popular, but it features high R&D cost and high clinical risk. There is still a certain degree of uncertainty from obtaining positive results in the Phase III interim analysis to submitting the marketing application and finally getting approval. Even if successfully approved, whether it can form comprehensive advantages among efficacy, safety, price and clinical accessibility will also determine its final market position.
In general, the positive interim PFS result of the SHR-A1811-307 study is an important progress in the R&D of domestic HER2 ADCs, indicating that local innovative drugs have the potential to directly challenge the internationally accepted first-line standard regimen.
However, a positive PFS result is only an admission ticket to enter the first-line market competition, not the final outcome. Subsequent OS data, complete safety results, benefit-risk ratio of the two regimens, registration and declaration progress and commercial performance are the core indicators to test the real value of trastuzumab rcanmisine. Whether it can truly rewrite the first-line treatment pattern of HER2-positive breast cancer still needs to wait for the complete study data to give the answer.
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