On May 2, the news that two domestic new drugs went to sea to fold the halberd has aroused widespread concern in the industry.
On the same day, Hehuang Pharmaceutical and Junshi Bio have disclosed that they have received a reply letter from the US FDA on its innovative drug listing application, and in the external announcement, the US FDA rejected the approval application of Junshi PD-1 triprulizumab and Huang Pharmaceutical Sofaminib, the former was required to make a quality control process change, the latter was rejected The reason is more "severe", the FDA said that its "existing clinical data is not enough to support approval".
Affected by this news, on May 2, Hehuang Pharmaceutical fell more than 22% at the opening of the market, and has since maintained a volatile downward trend, closing at $12.38 / share as of the close of May 4, a decline of 19.51%.
How should China's local pharmaceutical companies explore the "sea" road in the future?
and Huang Medicine's official website map
Behind the rejection of new domestic drugs: the lack of representation of single China data
"This result is actually not unexpected. The U.S. drug regulatory FDA's regulatory system does not support a single Piece of Chinese data. On May 5, a person in charge of a domestic innovative pharmaceutical company who did not want to be named told the People's Daily health client reporter.
According to public information, sofatinib is an oral tyrosine kinase inhibitor that was approved for listing in mainland China on December 30, 2020 for the treatment of patients with advanced non-pancreatic neuroendocrine tumors, and was approved as a second indication in June 2021 for the treatment of advanced pancreatic neuroendocrine tumors. In 2021, after medical insurance negotiations, sofatinib was included in China's medical insurance directory.
As the first independent innovation drug approved for the treatment of NET (rectal neuroendocrine tumor) in mainland China, and the second targeted drug in the world to treat non-pancreatic NET, sofatinib is not small. From 2019 to 2020, suffantinib has been granted orphan drug qualification and fast-track qualification by the US FDA. In June 2021, the application for a new drug submitted by Sofatinib in the United States was accepted, which caused the stock price of Huang Pharmaceutical to rise all the way, and now it is less than a year, and the situation is very different.
and Huang Medicine's official website map
What prevents Sofatinib from going to sea? According to the announcement issued by Hehuang Pharmaceutical, the response given by the US FDA said that the current data package based on two successful Chinese phase III experiments and a US bridging study is not enough to support the approval of the drug in the United States.
"There are multiple factors behind this decision, but the main one is the problem of data. The FDA is extremely concerned about whether the clinical data on the innovative drug submitted by the applicant can reflect the potential of the drug to meet the current unmet clinical needs in the United States and even the world. Xuan Jianwei, director of the Institute of Pharmaceutical Economics of Sun Yat-sen University, told reporters.
This is not the first time that new domestic drugs have been rejected due to "single China data" going to sea. In February, the U.S. FDA Advisory Committee on Oncology Drugs (ODAC) declined to approve the PD-1 monoclonal antibody jointly developed by Cinda Bio/Eli Lilly. ODAC believes that in addition to the lack of clinical data diversification in Innovent Biologics' trials, it has also failed to meet the US FDA's informed consent standards.
Earlier, in December 2021, Wanchun Pharma's punabulin was also stuck in a single clinical trial result, according to the disclosed data, 87% of the clinical data of purnabulin patients came from China, so the US FDA asked it to conduct a second trial.
The person in charge of the above-mentioned innovative pharmaceutical company explained to reporters that when the US drug regulatory department reviews data, the first threshold is 'representation', that is, whether the clinical trial data provided by the applicant is consistent with the current situation of the US patient population, so it is difficult to avoid international multi-center clinical trials. Second, the design and final results of clinical trials are very important, in the case of competition with similar products, the drug must prove to have a clear advantage in efficacy, safety and patient benefit rate, control group trials should be the first choice for the current US standard of disease therapy, and if necessary, head-to-head trials should be carried out.
"At the same time, in the process of applying for listing, the applicant must always maintain communication with the drug regulatory authorities on issues such as the design of the trial and the representativeness of the data, which is an easy but very critical strategy in the process of applying for listing." The person in charge of the above-mentioned innovative pharmaceutical company told reporters.
Learning from setbacks: Differentiated innovation capabilities are the key to success at sea
Image of the official website of the US FDA
"Globalization is the natural choice of mainland innovative pharmaceutical companies in the process of growth, but domestic new drugs going to sea, can not rely too much on imitation innovation and only in China's local market data and achievements, research and declaration procedures to fully meet the requirements of the US drug regulatory system, which means that innovative companies should invest a lot in clinical research." Xuan Jianwei believes that whether it can succeed in the end points to a problem that innovative pharmaceutical companies in mainland China cannot avoid: whether they have the ability to innovate with the comprehensive value of products.
In fact, there is no shortage of successful samples of innovative drugs in mainland China. In November 2019, the first domestic BTK inhibitor zebutinib developed by BeiGene was approved by the US FDA for listing, achieving a "zero breakthrough" in China's original anti-cancer new drugs, which once made the pharmaceutical circle boil. Two years later, in February 2022, Legendary Bio announced that its original CAR-T products were approved in the United States, and after the news was announced, LegendAry Bio's stock price on nasdaq rose by more than 12%.
The reporter inquired about the company's announcement and found that the first approval of zebutinib was based on the validity data of two clinical trials, namely the single-arm phase II clinical study BGB-3111-206 carried out in China, and the global phase I/II clinical trial BGB-3111-AU-003 in Australia. Higher than the then-marketed BTK inhibitors ibutinib or akatinib. The CAR-T product supporting legendary biology was finally approved as a Phase 1b/II international multicenter trial, in which patients with relapsed and refractory multiple myeloma received CAR-T infusion after multiple treatment, and the final results showed that the total response rate and complete response rate were 98% and 83%, respectively.
Intranet diagram
According to the statistics of The Intranet, at least 13 domestic new drugs have submitted listing applications to the US FDA. In the next trip to the sea, beigene and Kangfang bio's two PD-1 products have attracted much attention, two PD-1 listing applications have been accepted, and according to the BeiGene announcement, the results of its PD-1 product listing application are expected to be announced on July 11 this year.
What will be the end of domestic innovative pharmaceutical companies lined up to hold the "going to sea" number plate? The person in charge of the above-mentioned innovative pharmaceutical companies told reporters that with the development of science and technology, the level of pharmaceutical innovation has risen, and the drug regulatory rules of the US FDA are also constantly adjusting and tightening, but the ultimate goal of supervision has not changed, that is, how to leave limited resources for innovation that can fill the clinical gap, what pharmaceutical companies have to do is to strive to find the intersection with regulatory goals.
According to the announcement of Hehuang Pharmaceutical, Hehuang Pharmaceutical will actively cooperate with the US authorities to evaluate its feedback and continue to promote the listing application of sofatinib; according to the announcement of Junshi Bio, it is expected to resubmit the listing application this summer.
"China's new drugs are obstructed and long, and the line is coming." Personally, I do not think that the current temporary setback will evolve into a vicious circle, but believe that both domestic innovative pharmaceutical companies and capital will learn from 'failure'. In the past experience, both pharmaceutical companies and capital will prefer 'me-too' fast-follow-up products, and it is easy to abandon the need for long-term investment in 'first-in-class' with higher risks, as well as products that can fill the unmet clinical needs, but I believe that after these setbacks, both will become more calm and long-term, and the big wave of innovative drugs and innovative pharmaceutical companies is inevitable. Xuan Jianwei said.
Source: People's Daily health client
Author: Reporter Tan Qixin
Hot video recommendations
Pharmacy Zone of the Two Sessions
NPC deputies Li Suyan and Wang Jingcheng suggested speeding up the legislative process of the "Pharmacist Law of the People's Republic of China."
new
Pharmacist Policy Zone Selection
Reprinted and published by the pharmaceutical affairs network | Enjoy sharing the circle of friends | Please contact the authorization for reproduction
Pharmacy Network
China's leading Internet pharmacist group