FDA Issues Complete Response Letter for Merck’s sBLAs Seeking Six-Week Dosing Schedule for KEYTRUDA

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On February 18, Merck Sharp & Dohme (MSD) announced that the U.S. Food and Drug Administration (FDA) had issued Complete Response Letters (CRLs) for six supplemental Biologics License Applications (sBLAs) submitted by the company. These six sBLAs sought to update the dosing frequency of Keytruda to include a once-every-six-weeks (Q6W) regimen, specifically: 400 mg administered via intravenous infusion over no less than 30 minutes every six weeks, for multiple therapeutic indications.

Currently, the approved dosing regimen for Keytruda in the United States is 200 mg administered every three weeks. If the Q6W regimen ultimately receives approval, it will offer a more patient-friendly treatment option for cancer patients in the U.S., with reduced dosing frequency, thereby providing greater treatment flexibility for both patients and oncologists.

This application is based on the pharmacokinetic modeling and simulation data presented at the 2018 ASCO Annual Meeting. Based on these data, the European Commission approved the Keytruda 400 mg Q6W dosing regimen on March 28, 2019, for all previously approved monotherapy indications, covering eight therapeutic indications across five tumor types, including: non-small cell lung cancer, melanoma, bladder cancer, head and neck cancer, and classical Hodgkin lymphoma.

MSD stated that it is reviewing the complete response letter issued by the FDA and will discuss next steps with the agency.

To date, 10 PD-(L)1 therapies have been approved worldwide, with Keytruda emerging as the leader. It has gained approval for more than 20 indications, covering multiple cancer types across various treatment settings. Early this year, the FDA approved a new indication for Keytruda: monotherapy for patients with bacillus Calmette-Guérin (BCG)-unresponsive, high-risk non-muscle-invasive bladder cancer (NMIBC) with carcinoma in situ (CIS), with or without papillary tumors, who are ineligible for or have elected not to undergo cystectomy (bladder removal). Keytruda is currently the first and only anti-PD-(L)1 therapy approved for specific high-risk NMIBC.

According to the released performance reports, Keytruda’s sales exceeded $10 billion in 2019, reaching $11.048 billion, representing a significant increase of 54.1% from $7.171 billion in 2018. Bristol Myers Squibb’s Opdivo followed closely, also achieving record sales of $8.004 billion in 2019, a 5.8% increase from $7.567 billion in 2018.

Late last year, the pharmaceutical market research firm EvaluatePharma released a report predicting that in 2020, Keytruda would generate an additional $3.3 billion in sales, making it the drug with the highest expected incremental sales worldwide.

Reference Source: Merck Receives Complete Response Letter from the US FDA for Supplemental Biologics License Applications (sBLAs) for KEYTRUDA® (pembrolizumab) Six-Week Dosing Schedule