Patient Deaths Prompt the FDA to Suspend Three of Merck & Co.'s Keytruda Trials
July 6, 2017
By Alex Keown, BioSpace.com Breaking News Staff
KENILWORTH, N.J. – The U.S. Food and Drug Administration (FDA) placed a clinical hold on three trials studying Merck (MRK)’s PD-1 inhibitor Keytruda in combination with products developed by Celgene following Merck ’s initial reporting of several patient deaths in June.
On Wednesday, Merck said its Keynote-183, Keynote-185 and Keynote-023 trials were halted by the FDA after the Data Monitoring Committee discovered more patient deaths were observed in the Keytruda arm. Each of the trials is testing Merck’s drug as a combination treatment for the blood cancer multiple myeloma. Keynote-183 and Keynote-185 were placed on a full clinical hold, while Keynote-023 was placed on a partial clinical hold, Merck said. Patients in the trials have now discontinued treatment with Keytruda, according to the company.
In the Keystone-183 trial, Keytruda is being tested in combination with Celgene’s Pomalyst (pomolidomide). In the Keynote-185 trial, Keytruda is being tested in combination with Celgene’s Revlimid (lenalidomide). The Keystone-023 trial is examining the combination of Keytruda with Revlimid and the corticosteroid dexamethasone. In its announcement Merck said the FDA determined the risks of Keytruda combined with the two Celgene drugs “outweigh any potential benefit for patients with multiple myeloma.”
Keynote-183 is a Phase III study comparing pomolidomide (Pomalyst) and low-dose dexamethasone with Keytruda to pomolidomide and low-dose dexamethasone alone in patients with refractory or relapsed and refractory multiple myeloma (rrMM) who have undergone at least two lines of prior treatment.
Keynote-185 is a Phase III study comparing lenalidomide and low-dose dexamethasone with Keytruda to lenalidomide (Revlimid) and low-dose dexamethasone alone in patients with newly diagnosed and treatment-naïve multiple myeloma who are ineligible for autologous stem cell transplant (Auto-SCT).
Merck’s share prices fell about 1 percent in aftermarket trading Wednesday, dipping from the closing price of $64.16 to $63.47 per share. Celgene’s stock also took a nosedive in afterhours trading, dropping from $133.20 per share to $130.18. The Celgene stock did regain its losses.
“Patient safety is Merck’s primary concern, and we are grateful to the study investigators and patients involved in these studies for their commitment to this important research,” Roger M. Perlmutter, president of Merck Research Laboratories , said in a statement. “Merck’s development program for Keytruda, spanning more than 30 different tumor types, has one priority: helping patients suffering from cancer.”
Merck said the FDA’s clinical hold does not pertain to any of the other Keytruda trials in the clinic. Keytruda is involved in almost 500 clinical trials in more than 30 cancers and treatment settings.
Keytruda is a keystone drug for Merck. The PD-1 inhibitor has been approved to treat multiple types of cancer, including lung, bladder, melanoma and refractory classical Hodgkin lymphoma. In May, the FDA expanded Keytruda’s use by approving it for two new bladder cancer options. It was approved as a first-line treatment for patients with locally advanced or metastatic urothelial carcinoma who are ineligible for cisplatin-containing chemotherapy. Keytruda was also approved as a second-line treatment in locally advanced or metastatic urothelial carcinoma in patients who have disease progression during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.
Keytruda is not the only PD-1 inhibitor to see some troubles in clinical development. Bristol-Myers Squibb ’s Opdivo, as well as Genentech ’s PD-1 inhibitor Tecentriq have seen their share of troubles. Most recently Tecentriq flunked a Phase III bladder cancer trial and last year Opdivo failed to meet its endpoints in a Phase III trial as a monotherapy for a “broad patient population” in lung cancer.
There are currently five anti-PD-1 drugs on the market. In addition to Keytruda, Tecentriq and Opdivo, AstraZeneca has Imfinzi on the market. In May Merck KgaA and Pfizer saw approval for Bavencio.