Ivonescimab (SMT112, AK112), a first-in-class, humanized, tetravalent PD-1/VEGF bispecific monoclonal antibody, being internally developed by Akeso Biopharma (a China-based commercial-stage biopharmaceutical company), has shown exceptional results in late-stage HARMONi-2 clinical trial where it topped Merck’s blockbuster PD-1 binding checkpoint inhibitor Keytruda® in treating lung cancer. Akeso out-licensed Ivonescimab’s development and commercialization exclusive rights to Summit Therapeutics in the United States, Canada, Europe, and Japan.
Ivonescimab thus far has been approved only by China’s NMPA in May 2024 and no known PD-1-based bispecific antibodies have been approved by the US FDA or the EMA. 398 Chinese patients were tested in the clinical trials for metastatic colorectal cancer (mCRC) and this data was presented at the 2024 European Society for Medical Oncology (ESMO) Conference and IASLC 2024 World Conference on Lung Cancer (WCLC24).
The key differences between Ivonescimab and Pembrolizumab molecules include:
| Attribute | Ivonescimab | Pembrolizumab |
| Mechanism of Action | Targets both PD-1 (Programmed Cell Death Protein 1) and VEGF (Vascular Endothelial Growth Factor), making it a promising therapy for treating various cancers by both boosting the immune response and restricting the tumor’s ability to sustain itself. | Targets PD-1 (Programmed Cell Death Protein 1), a receptor found on T cells (a type of immune cell). |
| Therapeutic Indications | Approved in China for the treatment of non-small cell lung cancer (NSCLC), particularly in patients who have advanced or metastatic NSCLC | Approved for the treatment of metastatic non-small cell lung cancer (NSCLC) and advanced NSCLC, advanced head and neck squamous cell carcinoma (HNSCC), advanced melanoma and as adjuvant therapy for melanoma, and relapsed or refractory classical Hodgkin lymphoma (cHL) and refractory or relapsed primary mediastinal large B-cell lymphoma (PMBCL), among others. |
| Biological Sequence | Sequence can be found here | Sequence can be found here |
| Type of Antibody | Bispecific antibody | Monospecific antibody |
| Manufacturers | Akeso Biopharma | Merck |
Akeso’s Ivonescimab is protected by a molecule patent CN109053895 which is set to expire in 2038. The patent family includes 19 counterparts with protection in countries like the US, EU, Japan, Canada, Singapore, India, and Korea. Akeso is actively patenting CD73 inhibitors, lgG4 anti-CD47 antibodies, and anti-VEGFR2 monoclonal antibodies.
Some of its recent patent filings include:
| WO2024174990A1 | Fusion Protein Comprising Tgf-Βrii Extracellular Region Fragment, Pharmaceutical Composition Thereof And Use Thereof |
| WO2024162746A1 | Indole Compound Decomposing Ikzf2, And Use Thereof |
| WO2024136658A1 | Combination Treatment Of Cancers Using An Antibody That Binds At Least Egfr And An Immune Checkpoint Inhibitor |
| WO2023241629A1 | Anti-Cldn18.2 Antibody, And Pharmaceutical Composition And Use Thereof |
| WO2023208104A1 | Anti-Human Il-4ra Antibody And Application Thereof |
Can Ivonescimab be declared a cornerstone treatment already? – Not really!
Although it has been granted Breakthrough Therapy Designation (BTD) in China for the treatment of non-small cell lung cancer (NSCLC), experts suggest that much more clinical trial data is required and the current data is not sufficient to conclude as the assessment was based on China-focused patient population alone. It is unlikely that the US FDA will approve a drug stemming from this trial alone. There would be a requirement of a multiregional trial for approval consideration.
According to leading data and analytics company GlobalData’s analyst consensus forecast, Ivonescimab is projected to reach $1.7bn in global sales in 2030 while Keytruda®’s sales are forecast to peak in 2027 at $34.3bn and drop to $23.2bn in 2030. Merck already petrified about Keytruda®’s patent expiry in 2028, should also watch out for competition from approaching innovative therapies.