Merck KGaA halts Phase III trial for $1.08bn cancer drug

Merck KGaA has decided to halt the Phase III TrilynX trial, which was testing xevinapant in patients with unresected locally advanced squamous cell carcinoma of the head and neck (LA SCCHN). This decision was guided by an interim analysis conducted by an Independent Data Monitoring Committee, which indicated that the study was unlikely to meet its primary goal of extending event-free survival.

Xevinapant, an inhibitor of apoptosis protein (IAP) antagonist, was acquired by Merck from Debiopharm International in 2021 through a deal valued at $1.08 billion. The purpose of xevinapant is to make cancer cells more susceptible to programmed cell death. The news of the trial's discontinuation led to a more than 10% drop in Merck’s stock price on the Frankfurt Stock Exchange.

The TrilynX trial was a randomized, placebo-controlled study (NCT04459715) that included about 730 participants with LA SCCHN. It aimed to compare the effectiveness of xevinapant combined with chemoradiation therapy against a placebo with chemoradiation. The main endpoint of the trial was to measure event-free survival over a five-year period.

Despite the trial's cancellation, Merck noted that the safety profile of xevinapant was generally consistent with its role in enhancing the effectiveness of chemo-radiation therapy. The company plans to thoroughly review the trial data and release the findings in the future.

Xevinapant was considered a crucial part of Merck's oncology pipeline, particularly highlighted in the company's 2023 annual report. Its importance was underscored after Merck’s multiple sclerosis treatment, evobrutinib, failed to achieve its primary goals in Phase II trials.

In addition to xevinapant, Merck's oncology portfolio includes other promising therapies. These include HRS-1167, a selective poly (ADP-ribose) polymerase 1 (PARP1) trapping inhibitor, and SHR-A1904, a Claudin-18.2 antibody-drug conjugate (ADC). Merck licensed these therapies from Jiangsu Hengrui Pharmaceuticals, a Chinese company, under a deal worth up to $1.48 billion in October 2023.

Furthermore, Merck invested over €300 million ($320.8 million) in a new Life Science Research Center at its global headquarters in Darmstadt, Germany, in April. The center, slated to open in 2027, will focus on developing biopharmaceuticals, including antibodies and messenger ribonucleic acid (mRNA) applications.