After the heavyweight bomb Zebtinib, Baekje has received another ticket to enter the US market for a new drug.
On March 15th, BeiGene announced that its PD-1 product, Terezumab (trade name: Bazeon, TEVIMBRA), has been approved by the US Food and Drug Administration (FDA) for monotherapy in adult patients with unresectable or metastatic esophageal squamous cell carcinoma (ESCC) who have previously received systemic chemotherapy (excluding PD-1/L1 inhibitors). The product is expected to be launched in the United States in the second half of 2024.
In addition, the FDA is also reviewing two new indication applications for tirizizumab, which are used for first-line treatment of ESCC and for the treatment of gastric or gastroesophageal junction (G/GEJ) adenocarcinoma. It is expected that the decision will be made in July and December of this year, respectively.
However, on the same day of trading, the stock price of BeiGene opened high and then fluctuated and fell. As of the morning close, A-shares closed at 138.10 yuan/share, down 0.68%; H-shares closed at HKD 103.600 per share, down 2.72%.
Tirelizumab has also become the second domestically produced PD-1 to successfully sail to the United States. Prior to this, Junshi Biological's Treprizumab (trade name: Tuoyi, LOQTORZI) was approved in the United States in October 2023. In addition, tirelizumab was also approved in the European Union in September 2023.
In the current environment of domestic innovative drug payment, going abroad has become the optimal choice for Chinese innovative pharmaceutical companies in commercialization. Taking domestically produced new drugs that have entered the US market as an example, the pricing of Fuquitinib from Hehuang Pharmaceuticals and Treprizumab from Junshi Biotechnology in the US is 25200 US dollars per box (5mg * 21 tablets) and 8892.03 US dollars per bottle, respectively, which are about 24 times and more than 30 times the domestic pricing. The CAR-T therapy of Legendary Biology, Sidaki Orense, has a sales revenue of approximately 500 million US dollars in 2023, which is also a level unmatched by domestic CAR-T products.
Baekje's own Zebtinib achieved global sales of $1.3 billion in 2023. Among them, the US market contributed 946 million US dollars, a year-on-year increase of 142.6%, accounting for over 70%. During the same period, the sales revenue in the Chinese market was 194 million US dollars, a year-on-year increase of 28.9%.
As a broad-spectrum anti-cancer drug, PD-1 is also a rare variety. On March 14th, Wu Xiaobin, President and CEO of BeiGene, stated at a media communication meeting that the global PD-1 market size is approximately $50 billion, which is a percentage point of $500 million. This market capacity presents a great opportunity for BeiGene.
In fact, the process of using trezolizumab to go to sea has been full of twists and turns.
The overseas equity of tirizizumab was first sold to American pharmaceutical company Xinji, but in 2019, Baekje reclaimed the overseas equity of this product from Xinji. The reason is that Xinji was acquired by BMS, who holds O-drug and both sides collided on the PD-1 product.
By January 2021, Baekje will once again collaborate with multinational pharmaceutical company Novartis to jointly develop and commercialize tirizizumab in regions such as North America, Japan, and the European Union. Baekje received a prepayment of $650 million as a result, with a total transaction amount exceeding $2.2 billion.
In December of the same year, the scope of cooperation between the two parties expanded to include Esperazumab in Baekje. This is a TIGIT inhibitor that is considered the "next PD-1" by the market, and the development strategy of multiple MNCs is to combine it with PD-1 products. Therefore, this actually deepens the bond between Baekje and Novartis. Baekje also received an additional $300 million in advance payment.
But in 2022, Novartis announced that it would abandon the indications for non-small cell lung cancer and nasopharyngeal carcinoma for applying for tirizizumab in the United States. FDA also delayed the completion of the target review of the second-line treatment of ESCC indications for this product because the COVID-19 epidemic situation could not be completed in China.
Until July and September 2023, Esperazumab and Teralizumab were repeatedly returned by Novartis. On the same day, PD-1 rights were returned, and Baekje announced that the product had been approved in the EU market, with indications for second-line treatment of ESCC.
Regarding the abandonment of lung cancer as a major indication for application in the United States and being returned by Novartis, Wu Xiaobin stated at the time that due to Novartis's strategic adjustment, giving this PD-1 back to Baekje was a better choice. Additionally, according to Caixin, Wu Xiaobin mentioned the need to differentiate between the European and American markets.
Specifically, US regulations require certain conditions to be met and head to head studies to be conducted with local standard treatments. Due to considerations of time and cost, Baekje has not yet conducted head-on trials of tirizizumab with similar drugs. He admitted that it is difficult for the product to be successfully registered on major indications such as lung cancer in the US market.
But the drug regulations in Europe are different from those in the United States. In February of this year, Tirolizumab received positive feedback from the European Medicines Agency (EMA), recommending approval for its use in the treatment of three indications for non-small cell lung cancer.
In fact, Zebtinib in Baekje benefits from successfully expanding its indications. In January 2023, the drug was approved as a new indication in the United States for the treatment of relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (r/r CLL/SLL), entering this core niche market.
Previously, Zebutinib and Ibrutinib have achieved superior efficacy in Phase III studies on this indication, with the latter being the most widely used product among similar drugs. In March of this year, Zebutinib was also approved for use in combination with Otuzumab in the United States to treat adult patients with r/r follicular lymphoma (FL).
This may be related to the timing of drugs entering the market. When domestically produced PD-1 entered the US market, Merck's K-drug and BMS's O-drug had been on the market for nearly 10 years, occupying an absolute dominant position in similar products. In the BTK market, although Ibrutinib from Johnson&Johnson/Aberville was approved as early as 2013, it is the first generation BTK inhibitor. Subsequently, second-generation products such as AstraZeneca's Acotinib and Baekje's Zebutinib were approved in 2017 and 2019, respectively. The latter two have higher selectivity, fewer off target effects, and are easier to market share.
Furthermore, it is worth noting that compared to partnering with Junshi and Coherus, and partnering with Huang and Takeda to complete commercialization in the US market, Baekje has chosen a self built team to carry out commercialization in the US. Previously, the commercialization of Zebutinib was independently completed by the company. Considering the good sales performance of Zebutinib last year, the commercialization prospects of tirelizumab in the United States can still be expected.
In terms of performance, the 2023 performance report shows that the company's total annual revenue reached 2.5 billion US dollars, a year-on-year increase of 74%; The operating loss narrowed to $1.208 billion, a year-on-year decrease of approximately 33%; At the end of the reporting period, the company's cash reserves amounted to 3.2 billion US dollars. At the aforementioned media conference, Wu Xiaobin also mentioned that for the domestic market, he hopes to receive policy support, accelerate the admission of innovative drugs, explore more payment models, and expand the new drug market.