Merck KGaA Halts Xevinapant Phase 3 Head and Neck Cancer Trial

In 2021, Merck entered into a significant agreement with Swiss biotech Debiopharm, licensing the drug xevinapant for $855 million. Initially, Merck executives were optimistic about the drug's potential, particularly in treating locally advanced squamous cell carcinoma of the head and neck (LA SCCHN). As recently as last month, Merck's executives assured analysts that the failure of a phase 3 trial for xevinapant was “unlikely.” However, this optimism has now been dashed, leading to the halting of two critical studies involving the drug.

The TrilynX study was focused on evaluating xevinapant, an apoptosis protein inhibitor, in conjunction with chemoradiotherapy for patients with unresected LA SCCHN. In a May earnings call, Merck's Healthcare CEO Peter Guenter emphasized the adage "no news is good news" regarding the upcoming interim analysis of the trial. However, when pressed by an analyst, Guenter acknowledged the possibility of a worst-case scenario where the trial could fail.

This worst-case scenario was confirmed in a recent post-market announcement. The interim analysis concluded that the TrilynX study was unlikely to meet its primary goal of improving event-free survival. Merck acknowledged the challenges in treating LA SCCHN, noting that chemoradiotherapy has remained the standard care for decades despite numerous studies aimed at improving outcomes with new treatment approaches, including multiple immunotherapy trials.

The company disclosed that the safety data from the trial were generally consistent with the chemo-radio sensitizing properties of xevinapant. Despite the disappointing results, Merck reaffirmed its commitment to developing transformative oncology medicines for areas with high unmet needs. Danny Bar-Zohar, M.D., global head of R&D and chief medical officer for Merck’s healthcare business, expressed the company's determination to continue their oncology development efforts.

Additionally, Merck announced that it would halt another phase 3 trial of xevinapant, named the X-Ray Vision study, which involved patients who had undergone resection of locally advanced head and neck cancer. Inhibitors of apoptosis proteins, such as xevinapant, had been a cornerstone of Merck’s oncology strategy, alongside other innovative approaches like antibody-drug conjugates and DNA damage response kinase inhibitors.

Merck's commitment to the head and neck cancer community remains strong, supported by the EGFR inhibitor Erbitux, which it commercializes outside of the U.S. and Canada. Analysts at ODDO BHF had previously identified "blockbuster potential" in xevinapant and contextualized its failure within Merck's broader challenges, including the termination of its evobrutinib ambitions earlier this year.

The analysts regarded the failure of xevinapant as a significant setback, given that it was considered Merck’s strongest drug pipeline candidate for the near future. They noted that halting the trial was a major blow to Merck's objective of launching a meaningful drug every 1.5 years. Consequently, Merck's stock saw an 8% decline, trading at 153.65 euros on the Frankfurt Stock Exchange in the wake of the announcement.

In summary, Merck's recent challenges with the xevinapant trials highlight the difficulties in developing successful treatments for complex cancers like LA SCCHN. Despite these setbacks, the company remains committed to its oncology research and development, aiming to meet high unmet medical needs in the future.