Is it wrong after all?
Yesterday, Chi-Med announced that it has received a complete response from the US FDA on the use of surufatinib for the treatment of advanced neuroendocrine tumors letter. The FDA believes that the current data package based on two successful Phase III studies in China and a bridging study in the United States is insufficient to support the current approval of the drug in the United States. The full response letter indicates the need to include more international multicenter clinical trials representative of the U.S. patient population.
Not approved, need to supplement international multi-center phase III clinical trial The trial, the déjà vu, seems like it was just yesterday.
On February 11 this year, Innovent announced that the U.S. FDA convened the Oncology Drug Advisory Committee (ODAC). Discussion and voting on new drug marketing application (BLA) review issues for anti-injectable solutions. Ultimately, the committee voted 14:1 to recommend the need for additional clinical trials to demonstrate the applicability of sintilimab in the U.S. population and in U.S. medical practice prior to approval.
Trapped on the same rock twice, we don’t know if there’s anything in it, but it’s clear from previous announcements A clue.
In May 2020, Chi-Med stated that it had reached an agreement with the FDA at the pre-new drug marketing application meeting that surufatinib was used Two Chinese Phase III studies with positive results in patients with pancreatic and non-pancreatic neuroendocrine tumors, together with existing data from the U.S. bridging study of surufatinib, may form the basis for an NDA submission in the United States.
This “sweet date” from the FDA, Cinda can’t say that it has not received it.
“FDA Approval Reform Vane”, Richard Pazdur, Director of the FDA’s Oncology Center of Excellence (OCE), He once made a high-profile statement at the American Association for Cancer Research (AACR) annual meeting in April 2019: The United States welcomes China’s PD-1, even if there is only local clinical data in China, as long as the quality is good, the FDA will definitely open the door for it.
Disappointment or regret, it’s finally time to wake up. We have no way of knowing whether the inconsistent statements of the FDA are unilateral wishful thinking by pharmaceutical companies, or whether the FDA review standards are constantly advancing with the times; but what is certain is that only relying on the clinical trials of the Chinese center wants to knock on the door of the US FDA. It was an unrealistic adventure after all. If you want to make money on someone else’s site, you have to follow other people’s rules first. After all, the initiative is in the hands of the FDA.
Breakthrough Therapy/Fast Track
From 2017-2021, it can be seen from the FDA-approved drugs that both fast-track and breakthrough therapies account for a large proportion, reflecting The importance of early differentiation data for drugs.
Figure 1: 2017-2021 FDA-approved breakthrough therapy >
and Fast Track Proportion
Fast Track is designed to help develop drugs and accelerate A review of drugs that,show promise in treating serious or life-threatening diseases and address unmet clinical needs.
The type of information needed to demonstrate unmet clinical needs varies by stage of drug development: early in development, non-clinical data, machine theory Data or pharmacological data are sufficient; in future development, clinical data should be utilized. If there is an existing therapy, the rapidly qualified drug must show an advantage over the existing therapy, for example:
< span>(1) Shows excellent efficacy
(2) Avoids serious side effects or side effects leading to discontinuation p>
(3) For emerging or expected public health needs, etc.
The difference between a breakthrough therapy and a fast track is that a “breakthrough therapy” aims to Accelerating the development and review of new medicines to treat serious or life-threatening diseases. Its preliminary clinical evidence shows that there is a clinically meaningful endpoint that is substantially improved over existing drugs (Substantialimprovement). For the definition of substantial improvement, the FDA stated that it is necessary to examine both clinical treatment dimensions (such as the duration of drug effects) and clinical efficacy dimensions (such as disease response rate ORR), etc., that is, clear and clear advantages can be seen in preliminary clinical data. .
For the US FDA breakthrough therapy, a total of 470 items have been qualified in the ten years from 2012 to 2021, of which 240 items have been approved Successfully approved for marketing, considering that there are still many certified drugs that are still in clinical and marketing applications, the success rate of the drugs that have obtained breakthrough therapy qualifications will be higher than 50%. According to the report of Naturereview drugdiscovery, from 2010 to 2017, the probability of selected drugs from entering clinical phase I to being approved is about 6%-7%, and the probability from entering clinical phase II to being approved is about 6%-7%. It is 11%-15%, and the time period for the grant of breakthrough therapy is no later than the end of clinical phase II. It can be seen that the breakthrough therapy approved by preliminary data is expected to reflect a higher degree of success rate.
FIC (Firstin Class) drug p>
FIC (FirstinClass) drugs may not necessarily become blockbuster drugs, but most of the blockbuster drugs are FIC drugs. According to the FDA definition, a drug that has been granted an FIC is a drug that uses a new and unique mechanism of action to treat a disease. FIC drugs can be further divided into four categories:
(1) new targets (combinations) and new indications, if such drugs can It shows a good curative effect, and it is easier to obtain breakthrough therapy certification, and the single-arm method can often be used for registered clinical trials;
(2) The target (combination) is old, the indication is new, and the registered clinical reference (1), but sufficient proof of concept is required, especially when other drugs with related targets have no effect on the indication
(3) new targets (combinations), old indications, In terms of clinical registration, such drugs often require a head-to-head non-inferiority trial with the SOC of the indication. Of course, if the related drugs have shown obvious superiority compared with the existing SOC in early clinical trials, it is still possible to use Rapid approval in the form of breakthrough therapy;
(4) The target (combination) is old and the indication is This target drug is the first of its kind, and needs to consider (2) and (3) at the same time, and the market space it faces may also be relatively limited.
products with clear clinical benefit
Placing clear clinical benefit last is not because it is unimportant, but because its importance is generally recognized.
Cilta-cel is the only remaining fruit of recent innovative drugs going overseas. On March 1, GenScript announced that the BCMACAR-T product Cedarquiorenza, co-developed by Johnson & Johnson and Legend Bio, has been approved by the U.S. FDA for the treatment of adults with relapsed/refractory multiple myeloma patients (r/rMM).
In 2017, at the annual meeting of the American Society of Clinical Oncology (ASCO), Legend announced the then-codenamed Xida, which was still LCAR-B38M. Keo Lunsai, treatment of relapsed and refractory multiple myeloma patients, 100% overall response rate. Although only early clinical data, it is enough to shock the world.
The incidence of multiple myeloma is 2~4/100,000, and the male to female ratio is 1.6:1. It is common in middle-aged and elderly male patients. Although the continuous emergence of innovative therapies in the past decade has revolutionized the treatment of multiple myeloma, many patients will still relapse after remission and become resistant to existing therapies, eventually progressing to relapse and refractory disease Multiple myeloma is life-threatening. As a one-time infusion therapy, Cedarquiorenza is able to provide durable and deep remission in this patient population, has the potential to improve long-term survival, and provide hope and hope for patients who continue to receive treatment.
Hutchison Pharmaceutical’s failure to go overseas this time actually cleared the haze for innovative drugs to go overseas. Be down-to-earth, be brave in innovation, and solve unmet clinical needs. No shortcut is the best shortcut.
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