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A new class of in-development blood thinners are working to solve a long-time medical hurdle: how to prevent blood clots without causing bleeding, according to The Wall Street Journal (subscription).

What’s going on: “At least a half-dozen experimental blood thinners are in development that inhibit a protein called factor XI, one of several blood factors that regulate how the body forms clots. The challenge is this: The body generates two types of clots—good ones that plug holes in blood vessels to stop bleeding caused by external injuries, and bad ones that grow inside arteries and veins. These can block blood flow to critical organs, potentially leading to injury or death.”

• For many years, anticoagulants have targeted the proteins involved in both kinds of clots, which has meant they can contribute to higher bleeding risk. This has made many patients reluctant to take them.

Why it’s important: “[R]esearchers now believe that factor XI, unlike other blood factors, plays a minimal role in forming the good clots that stop bleeding. That suggests drugs against it could prevent the bad clots without significantly disrupting the process that causes good clots … minimiz[ing] excess bleeding.”

• For the past decade, drugs called Xa inhibitors—which “sharply reduce risk of life-threatening and other serious bleeding”—have become the standard anticoagulant for preventing stroke in certain patients with heart conditions. However, even with these bleeding remains a serious concern.   

Joining forces: Pharmaceutical manufacturers Bristol Myers Squibb and Johnson & Johnson have formed a partnership in the factor XI game, with milvexian, a twice-daily pill.

• “Their multibillion-dollar program includes Phase 3, or late-stage, trials for stroke prevention in atrial fibrillation and two other major indications—preventing recurrent events in patients who have already had an acute coronary episode such as a heart attack, or a stroke—with plans to enroll more than 46,000 patients. Milvexian targets the activated, or clot-initiating, form of factor XI, called factor XIa.”
• Pharmaceutical firm Merck also has an in-development agent aimed at clot-related illnesses.

More promise: “Low bleeding risk could also make factor XI inhibitors candidates to help prevent recurrent events in patients who have already suffered a stroke or an acute coronary event such as a heart attack—a potentially huge new market for anticoagulants.”