The 12th round of national Volume-Based Procurement (VBP) is underway, and Entresto (sacubitril/valsartan), familiar to many hypertension and heart failure patients, is once again being targeted after a narrow escape from last year's procurement list.

On May 15, Shanghai Sunshine Procurement Network published the "Announcement on Pre-filing of Drug Information for National Volume-Based Procurement." This round includes 77 varieties for pre-filing, totaling 233 specifications — the largest scale in history.

Among the varieties listed for pre-filing are several blockbuster drugs with annual sales of billions of RMB, including the immunosuppressant tacrolimus, the antiplatelet drug indobufen, and the antibiotic ceftazidime-avibactam. Most notably, sacubitril/valsartan sodium tablets — better known to hypertension patients as "Entresto" — has drawn the most attention.

"Entresto" was developed by Novartis. It is the world's first angiotensin receptor-neprilysin inhibitor (ARNI), with dual effects of lowering blood pressure and protecting the heart. It first entered the Chinese market in 2017 for heart failure treatment and was included in the national medical insurance catalog in 2020. In June 2021, it was also approved for treating primary hypertension in China, quickly replacing nifedipine as the new generation of antihypertensive "blockbuster." In 2025, Entresto's hospital market sales exceeded 6.2 billion RMB, with offline retail and e-commerce sales reaching 1.5 billion RMB, totaling nearly 8 billion RMB.

Such an attractive market naturally attracted a large number of generic drug companies. Sacubitril/valsartan is a compound preparation involving two types of patents: compound patents and combination patents. Domestic companies began attacking these patents early on. The compound patent was partially invalidated in January 2018, and Novartis's appeal did not change the result. The combination patent expired in July 2025.

To speed up generic development of sacubitril/valsartan, Chinese companies used a strategy of bypassing the still-protected polymorph patents. In fact, the first generic approval was obtained in 2023. The number of companies receiving generic approvals has been increasing rapidly. According to the Menei database, China now has 34 approvals for sacubitril/valsartan sodium tablets, with another 37 companies'marketing applications queued for review.

However, the remaining polymorph patent for sacubitril/valsartan is protected until November 2026, so very few generic companies can legally market their products. Only a handful of companies — such as Zhejiang Anglikang and Jiangsu Litai'er — have bypassed the key patent barriers, but they still cannot compete effectively with the originator product. Most generic manufacturers cannot market their products due to patent issues. Sacubitril/valsartan sodium tablets were included in the proposed 11th-round national VBP list but were ultimately removed due to patent concerns.

However, by the time of the 12th round of national VBP, the patent issue will no longer exist. The 12th round is expected to be implemented after November this year — after the patent has expired. This may be the first drugproduct to be included in VBP precisely at the patent expiration timeline.

Currently, Novartis is still applying for patent term extension for the polymorph patent of the hypertension indication of sacubitril/valsartan, and the application is still under review. If the extension is approved, this year's VBP may still face uncertainty.

The battle between dozens of companies over a single drug's generic development and VBP eligibility may be the most spectacular scene in VBP history. From aspirin — a century-old drug — to the "quasi-new drug" sacubitril/valsartan, which has not yet passed its patent period, China's VBP system is becoming increasingly precise in targeting drugs with high sales volume and high usage. Foreign pharmaceutical companies' product promotion strategies in China will need to continue adapting.