FDA Gives Merck Thumbs-Up for Two New Indications

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Merck & Company found itself with two new approvals this week. The U.S. Food and Drug Administration (FDA) gave it and AstraZeneca the thumbs-up for Lynparza for use as a maintenance regimen for adults with deleterious or suspected deleterious germline or somatic BRCA-mutated (gBRCAm or sBRCAm) advanced epithelial ovarian, fallopian tube or primary peritoneal cancer who are in complete or partial response to first-line platinum-based chemotherapy. That complex diagnosis is made in part with an FDA-approved companion diagnostic test.

The second approval for Merck was yet another nod from the FDA for its checkpoint inhibitor Keytruda. In this case, the anti-PD-1 therapy, Keytruda, was approved for adults and pediatric patients with recurrent locally advanced or metastatic Merkel cell carcinoma (MCC). This approval was based on results from the Cancer Immunotherapy Trials Network (CITN)’s CITN-09/KEYNOTE-017 clinical trial.

In the case of the Lynparza approval, it’s the first regulatory approval for a PARP inhibitor in the first-line setting for BRCAm advanced ovarian cancer. The data used for the submission came from the Phase III SOLO-1 trial. Lynparza reduced the risk of disease progression or death by 70 percent in BRCAm advanced ovarian cancer in patients who were in complete or partial response to platinum-based chemotherapy compared to placebo.

“The expanded approval of Lynparza based upon the SOLO-1 trial has the potential to change medical practice and reinforces the importance of knowing a woman’s BRCA status at diagnosis,” stated Roy Baynes, senior vice president and head of Global Clinical Development, and chief medical officer, of Merck Research Laboratories. “We continue to work in collaboration with AstraZeneca on our overall goal of improving outcomes for patients.”

The Phase II trial data used to support this indication looked at 50 patients with recurrent locally advanced or metastatic MCC who had not received previous systemic therapy. Keytruda by itself showed an objective response rate of 56 percent, with a complete response rate of 24 percent and a partial response rate of 32 percent. There will be confirmatory trials, because it was approved for this indication under accelerated approval based on tumor response rate and durability of response.

“The CITN-09/KEYNOTE-017 trial demonstrates that first-line treatment with anti-PD1 therapy provides a meaningful advance for Merkel cell carcinoma patients who have historically had a poor long-term prognosis,” stated Paul Nghiem, lead investigator, professor of dermatology at the University of Washington School of Medicine in Seattle and affiliate investigator at Fred Hutchinson Cancer Research Center.

Nghiem went on to say, “A few years ago, patients with Merkel cell carcinoma did not have treatment options beyond chemotherapy. As a practicing physician I am pleased that this approval provides another option for patients facing this rare and challenging disease.”

Earlier, Merck had a target action date of December 28, 2018 for its supplemental Biologics License Application (sBLA) for Keytruda in previously treated patients with recurrent or metastatic head and neck squamous cell carcinoma. The application was based on data from the Phase III KEYNOTE-040 clinical trial.

However, on October 22, the company released significantly improved overall survival data for Keytruda from its Phase III KEYNOTE-048 trial. The company stated at that point, with the data so good, it planned to file an sBLA for Keytruda for a first-line indication based on the KEYNOTE-048 data that will include data from KEYNOTE-040 as supportive data. “Based on these results,” the company stated, “Merck has withdrawn the sBLA for KEYNOTE-040 for KEYTRUDA as a second-line treatment in patients with recurrent or metastatic HNCSC, which was previously assigned a Prescription Drug User Fee Act (PDUFA) or target action date of Dec. 28, 2018.”