Bavencio, difficulty in expanding indication

Primary endpoint OS verification failure

The presence of alternative/follow-up treatment also affects

Will conclusions be different from Europe and the United States?

The possibility of approval for a renal cell carcinoma indication for Bavencio(Avelumab), an immunotherapy developed by Merck and Pfizer, is very low.

 

This is because the Central Pharmaceutical Affairs Review Committee of the MFDS has not recognized Bavencio's therapeutic effect.

 

The Central Pharmaceutical Affairs Review Committee held a meeting on October 29th, when Merck and Pfizer applied for Bavencio's indications for renal cell carcinoma, and whether the results of the clinical trials submitted were recognized as the agenda.

 

According to the results of the minutes released on the 9th, none of the six members who attended the meeting did not acknowledge the validity of Bavencio.

 

The committee members were cited on the basis of the existence of alternatives such as ▲not meeting the primary endpoint (OS) ▲alternative treatment and follow-up treatment.

 

One member said, "We believe it is reasonable not to approve the permit because Bavencio's OS results have not been met." He said, "The risk ratio of 0.79, which is the result of an interim analysis of overall survival (OS), is judged to be a clinically insignificant result.

 

This is 'JAVELIN Renal 101' study comparing the combination therapy of Bavencio and VEGF-based targeted anticancer drug Inlyta (Axitinib) with Sutene (Sunitinib) monotherapy, a standard treatment for renal cell cancer patients, to confirm the efficacy and safety.

 

According to the results of an interim analysis released last year, the Bavencio+Inlyta combination treatment group had a progression-free survival (PFS) of 13.8 months, significantly longer than that of the monotherapy group, 7.2 months, but the primary endpoint was 11.6 months each.

 

And 10.7 months, there was no significant difference.

 

The risk of disease progression and death was found to be 39% lower than that of monotherapy.

 

In the mid-term analysis, updated in April of this year, there was no significant difference in OS.

 

Accordingly, another member explained, "Because it did not show superiority compared to the conventional therapy, it was judged that the advantages did not appear when the two drugs were administered in combination." "Data should be presented to show that the addition of a follow-up therapy to an existing therapy improves over the existing therapy." Experts analyzed that the impact of clinical design and follow-up treatment would have had an impact.

 

One member said, "Pembrolizumab (Keytruda) and Nivolumab (Opdivo) have the same design and are approved for their significance in OS, but this drug did not." They said, "This drug is more affected by follow-up treatment than the two drugs, so it is judged that the OS did not come out well." According to the 3rd OS interim analysis, 12% of the combination therapy group and 44% of the control group received follow-up treatment.

 

During the follow-up therapy, more than 40% of the control group received immunotherapy.

 

The combination therapy group was 10%.

 

The company also explained, "It seems that these follow-up treatment factors have affected the OS." Even taking this into account, the committee members were negative about the approval.

 

One member pointed out that "The important thing in determining the success or failure of a study is whether or not the primary endpoint is satisfied, and adverse drug reactions of grade 3 or higher also tend to increase compared to the control group, so it cannot be evaluated as completely harmless." He said, "It is also very important that there are other drugs that have already proved the OS, and I think product approval or conditional approval is impossible." Another member also said, "When considering the follow-up therapy and other alternative therapies, the benefit that patients can receive is not confirmed, so the significance of treatment cannot be recognized." In addition, another member said, "There was a case where the indication was not obtained due to the failure to prove the benefit of OS in the first-line treatment of small cell carcinoma of Keytruda and the first-line treatment of non-small cell carcinoma of Tecentriq.

 

It is reasonable not to allow permission considering the fairness of the screening criteria for anti-cancer drugs." In the end, all six expert committee members concluded that the approval was not valid.

 

An official from the MFDS who attended the meeting also said, "When evaluating the OS, the test group receives 3 drugs including the second treatment, and the control group receives 2 drugs, so if the OS results of the test group and the control group are similar, it doesn't benefit the patient." As all of the Central Pharmaceutical Affairs Review Committee disapproved, it was difficult to obtain Bavencio's indication for renal cell carcinoma in Korea.

 

The Central Pharmaceutical Affairs Review Committee is an expert advisory body, and although the opinion of the Central Pharmaceutical Affairs Review Committee is not a decision of the MFDS, the opinion of the Central Pharmaceutical Affairs Review Committee is rarely reversed.

 

Meanwhile, Bavencio has acquired the indications for the first-line treatment of advanced renal cell carcinoma based on the research in Europe and the United States.

 

It has only indications for Merkel cell cancer in March last year in Korea.