Yangcheng Evening News reporter Chen Zeyun
Two months may clear cancer cells, and one injection will cost millions of yuan... In recent years, a new type of cellular immunotherapy called CAR-T has become a hot topic in the field of anti-cancer due to its high price and magical therapeutic effect. 's new star.
On this innovative drug research and development track, local Chinese companies compete with multinational pharmaceutical companies on the same stage, accumulating the kinetic energy of "overtaking on curves" and "sail out to sea".
Recently, the US FDA (US Food and Drug Administration) officially approved a CAR-T product, cilta-cel, which was independently developed by Legend Bio, targeting B cell maturation antigen (BCMA). It is also the first FDA-approved cell therapy product in China for the treatment of adult relapsed or refractory multiple myeloma (R/RMM).
This also means that in the field of CAR-T, China's innovative drugs have achieved "zero breakthrough".
The reporter learned that the price of Sidaki Orenza in the United States is US$465,000, equivalent to about 2.96 million yuan. Among similar products, this price is only lower than the US$475,000/needle of Novartis' Kymriah.
What enlightenment can the successful overseas launch of Sidaki Orunsai bring to the entire industry?
Local innovative drugs successfully knocked on the door of FDA
For a long time in the past, China's pharmaceutical development was mainly based on generic drugs or improved drugs, but now, local innovative drugs have begun to emerge on the international stage.
On February 28, Legend Bio officially announced in the United States that its self-developed cell therapy product, Sidaki Aurexa, was approved by the US FDA, becoming the first self-developed CAR-T product approved by the FDA in China. After BeiGene's anti-cancer drug BTK inhibitor "zanubrutinib" was approved in November 2019, the US FDA once again opened the door to Chinese innovative drugs. In the field of CAR-T, Chinese innovative drugs have achieved a "zero breakthrough" ".
According to public information, Legend Bio was established at the end of 2014 and is a subsidiary of the listed company Jinruisi.
In 2015, the company with an initial team of less than 10 people decided to focus on immune cell therapy.
"We don't want to do imitation and improvement, but to do real original innovation. To explore 'no man's land', we took a lot of risks." At a recent press conference, Dr. Fan Xiaohu, Chief Scientific Officer of Legend Bio, explained the original intention. .
How new is this track chosen by Legendary Creatures?
The full name of CAR-T is chimeric antigen receptor T cell immunotherapy, which is one of the most promising technologies in the field of global tumor treatment.
That is, after T cells are extracted from patients, they are transformed into CAR-T cells using genetic engineering technology in vitro, and after amplification, they are then infused back into the human body to identify and kill their own tumor cells.
In 2017, the world's first CAR-T cell product, Kymriah, was approved in the United States, opening a new chapter in the fight against tumors in humans.
It is generally believed in the industry that the successful opening of the FDA's door this time by Cidaki Orenza marks that China has reached the world's leading level in the field of new biological drug research and development, and is of great significance for boosting the confidence of Chinese pharmaceutical companies to go overseas.
When will it be available in the country?
With the approval of Sidakio Renxai, 7 CAR-T products including Kymriah have been approved in the world, most of which are targeting CD19 targets, and CAR-T targeting BCMA targets in the legendary bio-Sidakio Before the approval of Lunsai, only Abecma, developed by BMS and Bluebird, was approved by the FDA in March 2021.
In China, last year, two CAR-T products, Achilles Injection and Ruiki Orenza Injection, were launched. Among them, Achilles Injection is the product Yescarta introduced by Fosun Kite from the United States and combined with Technology transfer in China, authorized for localized production of targeted CD19 CAR-T products.
Ruiki Orenza Injection is a CD19 CAR-T product independently developed by the local pharmaceutical company WuXi Junuo on the basis of Breyanzi products in the United States.
In addition to the approval of Cidaki Orenza in the United States, its domestic listing progress and timetable have also become the focus of attention.
"Actually, we started clinical deployment in China and the United States at the same time, and there is no time difference." In this regard, Dr. Huang Ying, CEO and CFO of Legend Bio, said that Sidaji Orenza has been going global from the very beginning. The route of new drugs is to simultaneously apply for clinical trials at home and abroad.
However, due to the need for self-built commercial GMP production standards in China and the impact of the epidemic, the listing process lags behind compared with the United States.
"At present, we have enrolled many patients in China. According to our communication with CDE (the Center for Drug Approval of the State Food and Drug Administration), we may need to enroll some patients. We hope to complete the enrollment of these patients as soon as possible. We will continue to maintain communication and exchanges with CDE, and look forward to benefiting multiple myeloma patients in China as soon as possible." Huang Ying revealed.
11% more expensive than competing products, priced at $465,000 per needle
It is worth noting that after achieving the "zero breakthrough" in the overseas listing of domestic cell therapy drugs, Cidaki Orenza will face many challenges in order to successfully commercialize overseas.
Among them, Abecma, which was launched a year earlier than Sidaki Aurex, is also used for the treatment of multiple myeloid and is regarded as the most direct competitor of Sidaki Aureen.
How will Cidaki Orenza be priced after it is approved for marketing?
Do you need to fight price differentials to gain market share?
The reporter learned that the current price of Cidaki Orenza is 465,000 US dollars, which is within the price range of similar CAR-T products listed in the United States.
A reporter from the Yangcheng Evening News found that among similar products in the United States, this price is only lower than Novartis' Kymriah's $475,000/needle.
Compared with the direct competitor Abecma, Sidaki Orenza not only did not reduce the price, but showed a premium of about 11%.
Regarding why the price is so high, Huang Ying said: "Combining our current clinical trial evaluation and efficacy evaluation, the overall response rate of patients is 98%, and the two-year progression-free survival rate and overall survival rate are 61% and 74%, respectively. From In terms of the overall efficacy and treatment process, this price is relatively reasonable.”
"At the same time, we also take into account the patient's ability to pay. In the United States, whether it is commercial insurance or national medical insurance, including two government insurances for the elderly over 65 years old and low-income people, both are now officially approved by the FDA. CAR- T products have achieved coverage, and the price is set at US$465,000. This is also a consideration, which is based on comprehensive factors such as efficacy and differentiation." Huang Ying explained.
Legendary creatures do not seem to be worried about the next fierce market competition.
Fan Xiaohu also stated in public that whether it is "going overseas" for innovative drugs or domestically deploying innovative drugs, any relatively mature therapeutic area has limited head space. Therefore, the core key to obtaining a competitive advantage is always whether it can be achieved. Reflect the innovation of products, meet unmet clinical needs, improve drug accessibility, improve technology, indication selection, improve safety and efficacy and other dimensions, and break price competition through high-value innovation.
How can a drug take 8-10 years to “go overseas” with high investment and high risk?
A reporter from the Yangcheng Evening News noticed that, as a hot star track, many local pharmaceutical companies are also actively deploying CAR-T.
According to the statistics of the Lilac Garden Insight database, there are more than 20 domestic companies deploying CAR-T therapy. In addition to Legend Bio, Fosun Kite and WuXi Junuo, there are also Keji Bio, Reindeer Medical, Sibeman Bio, Innovent Bio, etc. .
The Huachuang Securities Research Report pointed out that in the research of CAR-T therapy, there is a possibility of overtaking on the curve in China, where the development of new drugs is gradually rising.
Up to now, the number of CAR-T clinical trials conducted in China has exceeded 500, ranking first in the world. This is also the first time that China has reached the international forefront in the field of new drug research and development.
Among them, Legend Bio's Sidaki Orenza and Keji Pharmaceutical's Claudin18.2 CAR-T have reached the world's leading level.
In addition, there are a number of companies that are deploying a new generation of CAR-T and allogeneic CAR-T technologies. The preliminary data is excellent and is expected to gain access to the global market.
"Currently, the research and development of innovative drugs for macromolecular and cell gene therapy in China is very active, but the development cost of this type of therapy is very high, and it is difficult to cover all the early development costs by relying on a single Chinese market alone, so there is a consensus in the industry. , to go overseas to develop the international market." Fan Xiaohu explained the necessity of "going overseas".
How "burning money" is the research and development of innovative drugs?
New drug development has the characteristics of long cycle, high risk and large investment. Generally speaking, the research and development of an innovative drug usually takes 8-10 years, and the investment cost is in the scale of 2 billion US dollars.
In this context, local pharmaceutical companies often need to "leverage" when developing overseas markets.
At the end of 2017, Legend Bio signed an exclusive global license and cooperation agreement with Janssen, a subsidiary of Johnson & Johnson, to jointly develop and commercialize Cidaki Orenza.
In the Greater China region, Legend Bio and Janssen will share the costs and benefits in a ratio of 7:3; in other regions of the world, the agreed ratio is 5:5.
Today, as of March 2022, Legend Bio has accumulated an upfront payment of $350 million and milestone payments of $250 million from Janssen.
"Currently in the US market, we and Janssen have five or five points in cost. In this cooperation process, we have invested a lot, but thanks to the cooperation with Johnson & Johnson, we can continue to grow and cultivate our own capabilities. Including early R&D to clinical, commercial production, GMP production, compliance registration and other links, the team actively participated and built the legendary ability from end-to-end drug design and development." Huang Ying said.
However, in his view, such a cooperation model is not the "only solution" for local pharmaceutical companies to go overseas.
Enterprises should choose partners with complementary advantages according to their own scale and situation.
Huang Ying suggested that if the company itself has the ability to invest in expansion, it can consider adopting a cooperation model such as Legend Bio and Janssen.
For many start-ups, they often lack funds, talents, experience and platform technology. They can also choose other cooperation models to focus more on research and development, and do not necessarily need to invest heavily in self-built clinical, production, registration and industrial production at an early stage. Ability.