O, K, I, T drug indications have been withdrawn one after another, or there will be more withdrawals...

In recent years, the FDA's approval of new drugs (and new indications) has been operating at a high level.

The immune checkpoint inhibitor PD-(L)1 has become a booster and main beneficiary of accelerated approval by regulatory agencies.

O drug Opdivo: SCLC

On December 31, 2020, Bristol-Myers Squibb (BMS) announced the withdrawal of its PD-1 monoclonal antibody Opdivo approved in the US SCLC indication market.

Opdivo is the first immune checkpoint inhibitor to enter the SCLC market and the first new small cell lung cancer drug approved in the past 20 years.

However, it hasn't been long to be happy with the good news, and bad news followed one after another.

K drug Keytruda: SCLC

On March 1, 2021, Merck announced that it would voluntarily withdraw an indication of its PD-1 monoclonal antibody Keytruda on the U.

On June 17, 2019, the FDA accelerated the approval of Keytruda for the treatment of SCLC patients.

As a result, researchers believe that Keytruda has shown ideal anti-tumor activity and long-lasting response in the treatment of SCLC, especially in PD-L1 positive patients.

However, in January 2020, Merck announced the results of a phase III clinical study called KEYNOTE-604.

I drug Imfinzi: bladder cancer

On February 23, 2021, AstraZeneca announced that the company voluntarily withdrew its Imfinzi as a second-line treatment indication for metastatic bladder cancer in the United States.

In May 2017, based on a phase I/II trial evaluating the safety and effectiveness of Imfinzi in advanced solid tumors (including previously treated bladder cancer), Imfinzi's tumor response rate and response continued in the Study 1108 trial Time data, and then get accelerated approval in the United States.

The transition from accelerated approval to full approval depends on the results of the DANUBE Phase III trial in the first-line metastatic bladder cancer indication, but unfortunately, the trial did not reach its primary endpoint in 2020.

T drug Tecentriq: metastatic urothelial carcinoma

On March 8, 2021, Roche announced the withdrawal of its PD-L1 antibody Tecentriq from the United States for the second-line treatment of metastatic urothelial carcinoma, and the withdrawal will not affect the use of Tecentriq's other approved indications.

In May 2016, Tecentriq was approved by the FDA for the second-line treatment of patients with locally advanced or metastatic urothelial cancer, becoming the first PD-L1 inhibitor approved by the FDA.

However, one year after Tecentriq received accelerated approval, its two confirmatory tests, IMvigor211 and IMvigor130, successively failed.

The purpose of accelerated approval is for serious or life-threatening diseases, and in the absence of effective treatments, the use of surrogate endpoint data that can predict clinical benefit is approved for marketing.

Looking back now, we may have overestimated the efficacy of PD-(L)1 drugs and overestimated our knowledge.
Later, in the head-to-head comparison of many indications, PD-(L)1 drugs were flattened by standard therapies.
Part of this agreement between consumers, payment departments and manufacturers to use AA drugs is their trust in the FDA, which is equivalent to the contract guarantor.
Now that the FDA pressures manufacturers to withdraw the non-advantageous label, it is responsible to patients and payment departments, and it also urges manufacturers to develop truly innovative drugs.
It is a win-win choice in the long run.

Reference source:

1.
DOI: 10.
1016/j.
jtho.
2019.
12.
109;

3.
https://endpts.
com/a-year-after-trial-failure-astrazeneca-withdraws-imfinzis-maiden-indication-in-bladder-cancer-but-execs-look-to-the-bright-side/ ；

4.