Bayer Halts Phase III Trial of Asundexian, Jeopardizing $5 Billion Annual Sales Outlook

On November 20, German pharmaceutical company Bayer announced it would terminate the Phase III clinical trial of its blood thinner asundexian due to its "lower efficacy" compared to Eliquis, which was co-developed by BMS and Pfizer. This prompted Bayer to halt the study early, while continuing to advance the drug’s development in another Phase III clinical trial.

Asundexian is a novel oral anticoagulant FXIa inhibitor that prevents pathological thrombosis by inhibiting Factor XIa, thereby preventing the recurrence of ischemic events. Bayer considers asundexian as the company's next-generation blockbuster anticoagulant drug. Earlier this year, company executives projected that asundexian’s ultimate annual sales would exceed $5 billion.

The termination of the Phase III clinical trial for asundexian is a significant blow to Bayer. Previously, Bayer's CEO Bill Anderson was implementing a comprehensive reform of the company, including reducing management and coordination layers to address its financial difficulties. However, due to this news, on the morning of the 20th, Bayer's stock plummeted by 18% on the Frankfurt Stock Exchange, falling below the 34-point mark.

Among anticoagulant drugs, Xarelto (Rivaroxaban), co-developed by Bayer and Johnson & Johnson, was once a blockbuster small-molecule drug in the global top 10 sales, with revenues of approximately $6 billion in 2022. However, in response to Xarelto's impending loss of patent protection in the coming years, Bayer began searching for a successor early on, with Asundexian emerging as its top candidate.

Bayer has high expectations for the development potential of asundexian. As an FXIa inhibitor, Bayer is confident in the safety of asundexian, firmly believing that it can prevent the formation of venous blood clots without increasing the risk of bleeding, offering the efficacy of Eliquis (apixaban) without adverse effects.

In the competition among anticoagulant drugs, the billion-dollar molecule Eliquis remains unbeaten in popularity. Co-developed by BMS and Pfizer, its sales reached $18.269 billion in 2022. However, with Eliquis' patent set to expire in the coming years, it will face the challenge of generic drugs capturing market share. If asundexian demonstrates superior efficacy in clinical trials compared to Eliquis, it holds significant market potential.

Asundexian has indeed gained favor. In 2022, asundexian received Fast Track designation from the U.S. FDA for secondary prevention in patients with non-cardioembolic ischemic stroke. In May 2023, asundexian, as a potential therapy for stroke and systemic embolism prevention in patients with atrial fibrillation, received Fast Track designation from the U.S. FDA once again.

However, despite high expectations, asundexian has shown mediocre performance in clinical settings. Although this drug can reduce the bleeding rate in patients with atrial fibrillation, it failed to meet the goal of reducing ischemic events in other Phase II clinical trials. In 2022, asundexian did not outperform the placebo in two mid-stage trials treating patients recovering from heart attacks and strokes, as the drug did not lower the combined incidence of silent brain infarction or ischemic stroke.

And now, asundexian has failed again in Phase III clinical trials. The Phase III clinical trial that Bayer terminated this time is named OCEANIC-AF, which was originally the first of three large-scale Phase III studies planned. The study aimed to compare the efficacy of asundexian with Eliquis in 18,000 atrial fibrillation (AF) patients at risk of stroke.

OCEANIC-AF randomly divided atrial fibrillation patients with stroke risk into two groups, receiving asundexian and Eliquis treatment respectively. The independent data monitoring committee considered that the efficacy of asundexian was inferior to the control group, thus recommending the termination of the trial.

In recent years, the market for oral anticoagulant drugs has continued to grow. As one of the leading options, FXIa inhibitors have a faster onset, a wider therapeutic window, and higher safety compared to the anticoagulant warfarin. Bayer's Xarelto and BMS/Pfizer's Eliquis are both representative examples of FXIa inhibitors.

Notably, as the patents for blockbuster drugs are about to expire, more emerging anticoagulants are beginning to appear. In addition to Bayer's asundexian, milvexian, a collaboration between BMS and Johnson & Johnson, is also expected to protect patients from stroke and reduce the risk of bleeding associated with FXa inhibitors.

SVB Securities analyst David Risinger said in a report in July this year that milvexian is BMS's "largest potential sales opportunity," with possible annual sales exceeding $5 billion, a possibility also acknowledged by BMS executives.

This means that Bayer and BMS will once again face off to compete for the oral anticoagulant drug market.

However, the development of a new generation of FXIa inhibitors has not been smooth. Asundexian encountered setbacks in clinical trials, and milvexian was no exception. In 2022, at the annual meeting of the European Society of Cardiology (ESC), BMS announced the interim results of milvexian's Phase II clinical trial. The data showed that it failed to meet the primary endpoint. This primary endpoint was a composite endpoint, measuring both the dose-response in terms of stroke incidence compared to placebo and the biomarker of cerebral infarction (i.e., lesions that may occur without a stroke). The final results showed that the drug did not achieve the composite endpoint.

The termination of the asundexian clinical trial may also raise doubts about the prospects of milvexian. BMS's stock price fell by 3% on the 20th.

Evercore ISI analyst Umer Raffat said in a client report that Bayer's statement would have a "very significant impact" on other companies in the field.

At present, Bayer and BMS remain confident in their respective products. BMS, in collaboration with its partner Johnson & Johnson, has designed a Phase III clinical trial to demonstrate the efficacy of milvexian.

As for Bayer, they plan to analyze the data to understand the reasons behind asundexian's underperformance and reevaluate another Phase III clinical trial, OCEANIC-AFINA.