Merck voluntarily withdraws Keytruda's indications for the treatment of patients with metastatic small cell lung cancer

5;">On March 1, Merck announced that the company would voluntarily withdraw Keytruda (pembrolizumab) in the United States for the treatment of patients with metastatic small cell lung cancer (SCLC), these patients in platinum chemotherapy and at least one other previous chemotherapy or The disease progressed afterwards.
According to reports, the withdrawal of this indication was completed after consultation with the U.
S.
Food and Drug Administration (FDA), and Merck is working hard to complete this change process in the next few weeks.
Merck said that this decision does not affect the use of anti-PD-1 therapy Keytruda for other indications.

5;">Based on the tumor response rate of KEYNOTE-158 (G group) and KEYNOTE-028 (C1 group) and the durability of response data, Keytruda was approved by the U.
S.
FDA for accelerated approval in June 2019.
However, whether to continue to approve the indication depends on whether the post-marketing requirements put forward by the regulatory authorities are completed-the advantages of Keytruda are determined based on the overall survival rate (OS).
In January 2020, Merck announced the results of the Phase 3 confirmatory trial KEYNOTE-604 for SCLC indications.
The trial reached one of the dual primary endpoints of progression-free survival, but for the other primary endpoint, OS, the trial did not reach statistical significance.
.

5;">Even seeing Merck’s failure to meet the standards, it took more than a year for the US FDA to finally determine that Keytruda should not be a treatment option for metastatic SCLC.
Merck and the U.
S.
FDA held consultations on this voluntary withdrawal as part of an industry-wide evaluation of accelerated approval indications that have not yet met the post-marketing requirements.
The "industry-wide assessment" mentioned by Merck may be a warning that the US FDA will not ignore those drugmakers who fail to deliver on their promises.

5;">At the same time, Merck is informing healthcare professionals that patients with metastatic SCLC treated with Keytruda should discuss their care with their healthcare provider.

5;">In recent months, not only Merck has suffered setbacks from the US FDA.
In late December last year, BMS wanted to promote the final approval of the checkpoint inhibitor Opdivo for third-line or higher-line treatment of SCLC, but confirmatory trials showed that Opdivo also showed similar failures in prolonging patient survival.

5;">According to the results of the Checkmate-451 and Checkmate-331 trials, Opdivo as a monotherapy and in combination with Yervoy failed to achieve the primary end point of OS.
BMS decided to withdraw in accordance with the US FDA’s recommendation on “following post-marketing scientific research evidence” Approve the application.

5;">In addition, AstraZeneca chose to abandon the indication of PD-(L)1 inhibitor Imfinzi in the treatment of bladder cancer in February.
In May 2017, the US FDA accelerated the approval of this indication for the first time.
The drug maker pointed out that this decision was made after "negotiations" with the US FDA, and cited similar "industry-wide evaluation" reasons.

5;">So, when confirmatory trials have been widely accepted as alternative endpoints by regulators, what lessons have the lessons of Merck and BMS taught the industry? The foreign media endpoint news website pointed out that the withdrawal of indications may depend on the field of treatment: in the field of oncology, the boundary between survival and death is clear.
But in other diseases, the data is not so simple.

5;">Private investor Brad Loncar said in an interview: “It is clear that the US FDA has put forward an initiative to require these tumor indications to meet operating standards.
This can maintain the fidelity of the accelerated approval concept.
A good thing.
But this situation may be less common in indications for rare diseases.
"

5;">For example, Sarepta's exon skipping therapy vyondys53 for the treatment of Duchenne muscular dystrophy received accelerated approval in December 2019.
In the case of exerting an effect on motor function, it may be much more difficult for the US FDA to withdraw treatment from a group of patients with rare diseases.
The same situation applies to multiple sclerosis drugs.
However, if the US FDA takes a serious stance on the regulations that must be implemented after its drugs are marketed, it may eventually usher in a big liquidation.
(Medicine first time)