Merck KGaA drops xevinapant with phase 3 head and neck cancer trial on course for failure

Just last month, Merck KGaA executives were reassuring analysts that the failure of a phase 3 trial of xevinapant was “unlikely.” Now that worst-case scenario has come to pass. The company will now halt both studies on what was once a key brick in the German pharma’s oncology wall.

The TrilynX study was evaluating the apoptosis proteins inhibitor alongside chemoradiotherapy in patients with unresected locally advanced squamous cell carcinoma of the head and neck (LA SCCHN). In an earnings call with analysts in May, Merck’s Healthcare CEO Peter Guenter said “no news is good news” when it came to the upcoming pre-planned interim analysis of the study.

Only when pushed by an analyst on the May 15 call did Guenter admit that there was also a “worst-case scenario” where the company would be forced to divulge that the trial was heading for failure.

Merck has now confirmed the worst case in a post-market announcement yesterday, disclosing that the interim analysis has concluded that the TrilynX study is unlikely to meet its primary objective of prolonging event-free survival. The company said that LA SCCHN has “proven to be a difficult-to-treat form of cancer.”

“Chemoradiotherapy has remained the standard of care for decades, despite multiple studies designed to improve outcomes with new treatment approaches, including multiple immunotherapy trials,” the company pointed out in the June 24 release.

Topline safety data from the trial were “overall compatible with the chemo-radio sensitizing properties of xevinapant,” Merck added.

“While we are disappointed by these results, we remain steadfast in our commitment to develop transformative medicines within our oncology portfolio for areas of high unmet need,” Danny Bar-Zohar, M.D., global head of R&D and chief medical officer for Merck’s healthcare business, said in the release.

The company added that “given the totality of the data,” another trial of xevinapant will be halted—the phase 3 X-Ray Vision study in patients who have undergone resection of locally advanced head and neck cancer.

Inhibitors of apoptosis proteins, in the form of xevinapant, had been one of the pillars of Merck’s oncology pipeline, alongside antibody-drug conjugates and DNA damage response (DDR) kinase inhibitors.

Merck licensed xevinapant back in 2021 via a $855 million pact with Swiss biotech Debiopharm. A year later, Bar-Zohar was specifically highlighting the Debiopharm agreement as the kind of deal the company hoped to replicate.

In yesterday’s release, Merck stressed that its support for the head and neck cancer community “remains steadfast” thanks to the EGFR inhibitor Erbitux, which the pharma commercializes outside of the U.S. and Canada, where it is marketed by Eli Lilly.

Assessing the impact of xevinapant's failure, analysts at ODDO BHF said they had identified “blockbuster potential” in the candidate and put the drug's failure in the context of the end of Merck's evobrutinib ambitions in March.

“The failure of xevinapant is clearly very negative as the drug was seen as the strongest drug pipeline candidate for the near future of the company,” the analysts wrote in a June 25 note. “The stop is a further major setback for Merck and counteracts its objective to launch a meaningful drug every 1.5 years.”

Merck's stock was trading down 8% at 153.65 euros on the Frankfurt Stock Exchange as of 2:18 pm local time.