The subcutaneous formulation of Keytruda has been approved, covering 19 solid tumor indications.

PD-1 Competition Shifts to Administration Efficiency and Patient Experience

On September 29, the subcutaneous injection formulation of Merck's PD-1 inhibitor Pembrolizumab Injection was approved by the National Medical Products Administration.

The administration duration of this agent is drastically shortened to the minute level compared with intravenous infusion, marking that China's oncology immunotherapy has extended its competition from therapeutic efficacy to efficiency and experience.

The Anti-tumor Mechanism Remains Unchanged

The subcutaneous injection formulation of Pembrolizumab covers 19 solid tumor indications, making it the first and currently only PD-1 inhibitor with a subcutaneous injection formulation approved in China.

Pembrolizumab, widely known in the industry as "Keytruda", blocks the binding of PD-1 to its ligands to lift the suppression of tumor cells on the immune system.

Since entering the Chinese market in 2018, its indications have been expanded to multiple tumor types including melanoma, lung cancer, esophageal cancer, gastric cancer, liver cancer, breast cancer, and biliary tract cancer, and its treatment scenarios have gradually extended from late-stage medication to perioperative and early-stage treatment.

The newly approved subcutaneous formulation consists of Pembrolizumab and the hyaluronidase variant Berahyaluronidase alfa. The latter can improve the permeability of subcutaneous tissue, help the dispersion and absorption of high-dose antibody drugs, thus eliminating the intravenous infusion process.

Its anti-tumor mechanism has not changed, and its core value lies in the upgrade of administration mode.

For Merck, the subcutaneous formulation is also a key layout to extend the life cycle of its core product.

In 2025, the total global sales of Pembrolizumab and its subcutaneous injection formulation reached 31.68 billion US dollars, a year-on-year increase of 7%, accounting for nearly half of Merck's total annual revenue of 65 billion US dollars.

In the second quarter of 2026, the two formulations generated combined sales of 8.4 billion US dollars, of which the subcutaneous formulation Keytruda Qlex contributed 463 million US dollars.

Administration Shortened to Minute Level

The main evidence for the approval of the subcutaneous formulation comes from the Phase III study MK-3475A-D77. The study enrolled treatment-naive patients with metastatic non-small cell lung cancer, and conducted a head-to-head comparison between the regimen of subcutaneous Pembrolizumab combined with chemotherapy and the regimen of intravenous Pembrolizumab combined with chemotherapy.

The study met two key pharmacokinetic endpoints, namely that subcutaneous administration was non-inferior to intravenous administration in both the drug exposure in the first cycle and the steady-state trough concentration.

In terms of efficacy, the objective response rates of the subcutaneous group and the intravenous group were 45.4% and 42.1% respectively, the median duration of response was 9.1 months and 8.0 months respectively, and the median progression-free survival was 8.1 months and 7.8 months respectively.

In terms of safety, the incidence of grade 3 and above adverse events in the two groups was 47.0% and 47.6% respectively, with similar overall safety profiles.

These data show that the subcutaneous formulation is comparable to the intravenous formulation in terms of drug exposure, efficacy and safety, but it cannot be considered that its efficacy is better. The main change it brings is in the treatment process.

According to the approved regimens overseas, it takes about 1 minute for the subcutaneous formulation when administered once every three weeks, and about 2 minutes when administered once every six weeks, while the traditional intravenous formulation usually requires about 30 minutes of infusion.

Relevant studies show that after the adoption of subcutaneous administration, the chair-side stay time of patients is reduced from 117.2 minutes to 59.0 minutes, the total stay time in the treatment room is reduced from 126.9 minutes to 66.7 minutes, and the activity time of medical staff for preparation, administration and monitoring is reduced by 45.7%. The actual medication method in China shall be subject to the approved instructions.

Market Growth Remains to Be Seen

The subcutaneous formulation can reduce the number of intravenous punctures and cut down waiting time, and the improvement of convenience is more prominent for patients who need long-term immunotherapy.

For large oncology centers, the shortened administration time also helps improve the turnover efficiency of infusion chairs, pharmacy dispensing centers and nursing staff.

It should be noted that Pembrolizumab is not the first subcutaneous immune checkpoint inhibitor in China. The PD-L1 inhibitor Envafolimab was already approved domestically in 2021.

This approval of Pembrolizumab is the first subcutaneous PD-1 inhibitor in China, and the two are different in targets, indication coverage and clinical evidence.

From the perspective of industry trend, the competition of antibody drugs is expanding from efficacy and indications to administration efficiency. Products such as Roche's Atezolizumab and Bristol Myers Squibb's Nivolumab have also launched subcutaneous formulations in some overseas markets.

As PD-1 and PD-L1 drugs gradually enter the mature stage, shortening administration time and improving patient experience are becoming new differentiated directions.

However, product approval is only the starting point of commercialization. Whether the subcutaneous formulation can be included in the medical insurance and hospital catalogs, what price difference it will form with the intravenous formulation, and whether medical institutions are willing to adjust the existing diagnosis and treatment processes will all affect its growth pace.

For patients who still need combined intravenous chemotherapy, the chemotherapy infusion process cannot be completely eliminated, and the time advantage brought by the subcutaneous formulation will also be reduced accordingly.

Subcutaneous injection does not mean that patients can administer the drug by themselves. Pembrolizumab may still cause immune-related adverse reactions, and the subcutaneous formulation also needs attention to local injection reactions, allergies and administration-related systemic reactions. The administration operation must be performed and monitored by professional medical staff.

If the price, access and safety management can be synchronized, this subcutaneous formulation is expected to convert minute-level administration into a more efficient diagnosis and treatment process, providing new treatment options for patients and medical institutions.

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