Event: on February 10, FDA held an ODAC meeting. At the meeting, Cinda biology and Lilly’s PD-1 monoclonal antibody cindilimab’s BLA application failed with a vote of 1:14. The voting result of the ODAC meeting held that cindilimab needs to supplement clinical trials to support its approval in the United States. Generally speaking, FDA will make a final review decision according to the voting result.
This ODAC meeting provides the first reference case for domestic innovative drugs to go to sea in the future, explains in detail the focus of FDA’s attention, and points out the realization path for other domestic innovative drugs to be approved by FDA and listed in the United States in the future. According to the information disclosed at the ODAC meeting, the main reasons why the BLA failed to vote at the ODAC meeting are as follows. We believe that these problems pointed out by FDA point out the realization path for domestic innovative drugs that want to be approved for listing in the mainstream markets of Europe and the United States in the future:
(1) Cinda biological orient-11 research is only carried out in China, not a multi regional clinical trial, which fails to reflect the differences between Chinese and American patients and the diversity of ethnic groups in the United States: This requires that domestic innovative drugs that want to be approved for listing overseas must carry out global multi center clinical trials and include different patient groups to explain the differences between different human species, We expect that there will be two modes for domestic innovative drugs to carry out global multi center clinical trials in the future. One is that enterprises spend a lot of money to carry out phase 3 clinical trials overseas, such as Baiji Shenzhou; The second is to authorize MNC at a reasonable price at an early stage to cooperate with MNC in overseas clinical development, such as car-t of legendary biology.
(2) the control group is not the standard therapy of the United States, and the setting of PFS, the main endpoint of the study, is not in line with the clinical practice of the United States: This requires that domestic innovative drugs that want to be approved for listing abroad should pay attention to the current standard therapy of the United States when designing the clinical trial scheme. We think we should pay attention to two points in the whole process of clinical trial design and implementation, First, actively communicate with the regulatory authorities before setting up the control group to explore the possibility of future regulatory approval when setting up different control groups; Second, the implementation of specific clinical trials should be fast, not later than the listing time of the latest standard therapy.
(3) lack of FDA consultation and supervision: This requires relevant enterprises to pay attention to communication with regulators in the whole process from ind stage to listing.
(4) failure to supplement unmet clinical needs in the United States: this means that some unmet clinical needs in the United States may be handled flexibly by regulators. In the future, the listing application of such drugs and indications in the United States is expected to get more flexible processing space from FDA.
We believe that the setback of Cinda bio PD-1 at sea does not change the prospect of the whole domestic innovative drugs at sea, but makes it possible for domestic innovative drugs to go to sea in the future. Driven by the huge market space in the overseas pharmaceutical market, we expect the following three types of enterprises to realize their products at sea and dig into the mainstream pharmaceutical markets in Europe and America in the future:
(1) enterprises with abundant funds, enough courage and confidence to promote phase 3 clinical trials in overseas markets dominated by European and American markets: such as Baiji Shenzhou, Jiangsu Hengrui Medicine Co.Ltd(600276) and so on. We believe that such enterprises have great advantages in promoting phase 3 clinical trials in Global Multi centers. The reason is that these enterprises are based in China and a considerable majority of patients can be recruited from China compared with MNC, It has considerable advantages in clinical promotion speed and clinical trial cost.
(2) enterprises with strong scarcity of products or outstanding clinical efficacy that have the potential to authorize varieties to MNC: such as legendary Biology (BCMA car-t), Keji Pharmaceutical (cldn18.2 car-t), Yasheng Pharmaceutical (Bcl-2 inhibitor, MDM2-p53 inhibitor), Kaifa Pharmaceutical (forritain for androgen alopecia) Kangfang Biology (PD-1 / CTLA-4 double antibody, PD-1 / VEGF double antibody, CD73 monoclonal antibody, CD47 monoclonal antibody), Xinda Biology (LAG-3 monoclonal antibody), Tianjing Biology (CD47 monoclonal antibody, CD73 monoclonal antibody), etc.
(3) the products can supplement European and American enterprises that do not meet the clinical needs: such as Shanghai Junshi Biosciences Co.Ltd(688180) (indication of PD-1 monoclonal antibody for nasopharyngeal carcinoma), Hehuang medicine (indication of sufantinib for pancreatic and extrapancreatic neuroendocrine tumors), etc.
Risk warning: the risk of innovative drug products going to sea is less than expected, and the risk of China’s relationship affecting the FDA review policy.
