Recently, BeiGene announced that its PD-1 inhibitor Trastuzumab (US trade name: TEVIMBRA) has been officially commercialized in the United States for the treatment of adult patients with unresectable or metastatic esophageal squamous cell carcinoma (ESCC) who have previously received systemic chemotherapy (excluding PD-1/L1 inhibitors).

Global pharmaceutical companies consider the US market as a battleground for going global. At the end of October 2023, Junshi Biotech's trastuzumab (US trade name: LOQTORZI) obtained FDA approval, becoming the first nasopharyngeal carcinoma drug to be marketed in the United States, as well as the first biologically innovative drug and PD-1 inhibitor from China approved by the FDA. In March 2024, BeiGene's Trastuzumab was approved for its first indication in the United States, following closely behind.

After more than six months of FDA approval, Trastuzumab has finally been officially launched for sale in the United States. In the industry's view, Chinese pharmaceutical companies such as Junshi Biotechnology and BeiGene are constantly expanding their international markets, reflecting the continuous maturity of domestic PD-1 drug technology and the growing global ambitions of the companies. In the future, the PD - (L) 1 inhibitor race will attract more participants, but competition will no longer be limited to the domestic market, but will develop towards internationalization and globalization.

Due to differences in pricing systems for innovative drugs in different countries, an innovative drug entering different markets will be priced according to the local market system. It is reported that BeiGene has lowered the pricing of Trastuzumab by 10% compared to other approved PD-1 therapies for this indication, in order to improve drug accessibility. According to reports, a spokesperson for BeiGene revealed that the average wholesale purchase price for Trastuzumab is estimated to be $15075 per month (approximately RMB 106300).

The other approved PD-1 therapies for this indication mentioned above include Merck's Keytruda (pembrolizumab, commonly known as "K-drug") and Bristol Myers Squibb's Opdivo (nivolumab, commonly known as "O-drug"). It is reported that K drug with a specification of 100mg/4ml is priced at $4800 (approximately 33000 RMB) in the United States; The price of O drug with a specification of 240mg in the United States is approximately $6500 (about 46000 yuan).

In the industry's view, the pricing of Trastuzumab in the United States is lower than that of similar products, possibly with the aim of competing for the market at a low price. In addition, the degree of clinical benefit is also one of the factors determining the pricing of new drugs. The approval of Trastuzumab for marketing in the United States is based on the results of the RATIONALE 302 trial, which achieved the primary endpoint in the intention to treat (ITT) population.

Compared with chemotherapy, Trastuzumab demonstrated statistically significant and clinically significant survival benefits. But K and O drugs have long dominated the US market, with a first mover advantage. Other latecomers may only gain a glimmer of hope by entering the market at a low price.

As one of BeiGene's two core self-developed products, Trastuzumab has contributed significantly to its performance. In the second quarter of 2024, the sales revenue of Tilelizhu was 158 million US dollars, a year-on-year increase of 6%. In the first half of the year, the total reached 303 million yuan, a year-on-year increase of 14.9%. The increase in sales of Trastuzumab is mainly due to the new indications being included in medical insurance, which has brought about new patient demand and an increase in the number of drugs admitted to hospitals. At present, Trastuzumab has been approved for 13 indications in China, and 11 indications have been included in the national medical insurance catalog, widely covering high-risk cancer types such as lung cancer and liver cancer in China.

Compared to the impressive financial report data, the path of Trebizumab entering the US market has not been smooth sailing. As early as January 2021, BeiGene and Novartis reached a cooperation and authorization agreement for the development, production, and commercialization of Trastuzumab in multiple countries worldwide, with a total transaction amount of 2.2 billion US dollars, setting a record for the highest single drug authorization transaction amount in China at that time. In September of the same year, BeiGene submitted a marketing application for the second-line treatment of ESCC with trastuzumab to the FDA, with a PDUFA date of July 12, 2022.

However, the sudden outbreak of the epidemic has blocked the marketing process of Trastuzumab in the United States. On the evening of July 14, 2022, BeiGene announced that due to travel restrictions related to the pandemic and other factors, the FDA was unable to complete the required on-site verification work in China as scheduled, and therefore would extend the target review completion time for the new drug approval application (BLA) for Trastuzumab.

Faced with the ever-changing international market and competitive landscape, BeiGene's partner Novartis has changed its mind. In September 2023, BeiGene suddenly announced that it had decided to terminate its overseas licensing deal with Novartis and regain global development, production, and commercialization rights for Trastuzumab. The termination of the contract means that BeiGene will be solely responsible for conducting business related to the listing of Trastuzumab in the United States.

After nearly two years, Trastuzumab finally knocked on the door of the US FDA in March 2024. This is also the second domestically produced PD-1 product to successfully go to the United States after Junshi Biotechnology. Industry insiders believe that the market size of PD-1 drugs in the US market is about 50 billion US dollars, and the successful entry of domestic PD-1 drugs into this market means that they can share a huge market cake. The launch of Trastuzumab in the United States is not only of great significance for the commercial development of BeiGene, but also has a positive impact on promoting the internationalization of innovative drugs in China and global patient treatment choices.

Public data shows that over the past five years, the global market performance of PD - (L) 1 inhibitors has been remarkable, with a compound annual growth rate of 45%, which is three times the overall tumor market growth rate. With the continuous maturity of the PD - (L) 1 inhibitor market, it is expected that its compound annual growth rate will slow down to 15% in the future. Some institutions predict that by 2025, global sales of PD - (L) 1 inhibitors will increase to $58 billion. Although this growth rate is relatively low, it is still higher than the overall tumor market's expected compound annual growth rate of 10%.

Despite the considerable size of the global market, the market competition for PD - (L) 1 inhibitors remains fierce. As of the first half of 2024, 15 PD - (L) 1 inhibitor drugs have been approved for market in China. In addition, there are over 600 registered clinical trials of PD-1/PD-L1 drugs in China, involving more than 150 companies, of which nearly 200 have entered the phase III clinical stage.

Local pharmaceutical companies that already have PD-1 products are seeking international development and differentiation in order to occupy a place in the market. At present, two domestically produced PD-1 drugs have been approved for market in Europe and America, namely BeiGene's Trastuzumab and Junshi Biotech's Triprolizumab.

It is worth mentioning that Hengrui Pharmaceutical's Carilizumab is expected to become the next domestically produced PD-1 drug to be launched and sold in the United States, following Junshi Biotechnology and BeiGene.

However, Hengrui Pharmaceutical's Carilizumab has also encountered many setbacks in its listing process in the United States. In May of this year, Hengrui Pharmaceutical announced that it had received a complete response letter from the FDA regarding the biological product approval application (BLA) for the first-line treatment of unresectable or metastatic hepatocellular carcinoma patients using the combination of Carilizumab and Apatinib.

In the reply letter, the FDA stated that it will conduct a comprehensive evaluation based on the company's complete response to the inspection defects at the production site; And due to travel restrictions in some countries, the FDA stated that it is not possible to complete all the necessary biological research monitoring plan (BIMO) clinical examinations for the project during the review period. Hengrui Pharmaceutical stated at that time that the company plans to actively maintain close communication with the FDA and resubmit the marketing application as soon as possible, in order to obtain approval for the product to be launched in the United States as soon as possible.
According to industry insiders, the complete response letter, also known as CRL in the industry, will be detailed by the FDA regarding possible defects and risks, and provide suggested solutions. If the applicant can complete the changes within the specified time, it will not actually affect the final approval. That is to say, the US listing process for Hengrui Carilizumab is only delayed.

In the industry's view, the overseas launch of PD-1 drugs is not the end point, and their commercial success and profitability are equally important.

Recently, Coherus, the US partner of Junshi Biotechnology, released its Q2 2024 performance report. Among them, the commercial sales of Junshi PD-1 Terriptylimab (Loqtorzi), which cooperates with Junshi Biology, reached 3.8 million US dollars in the second quarter of the year in the United States, a significant increase of 90% compared to its net sales of 2 million US dollars in the first quarter.

In early 2024, Cohurs plans to focus on the tumor microenvironment and a high potential product line complementary to the PD-1 pathway, with Terizumab as the backbone of its combination studies with novel drugs. Cohurs predicts that the peak sales of Triprolizumab in the single indication of nasopharyngeal carcinoma will reach $200 million, expected to be achieved in 2-3 years; And by 2032, the sales of Triprolizumab are expected to approach $2 billion.

Despite the increase in sales of trastuzumab promoted by Cohuersu, there is still a significant gap compared to the expected peak sales. This may be related to the relatively small number of patients with recurrent, locally advanced, or metastatic nasopharyngeal carcinoma (NPC) for which trastuzumab has been approved in the United States. Its commercialization progress in the United States is still relatively slow, and there is still a long way to go in the future.

Source: https://pharm.jgvogel.cn/c1449464.shtml