Widely prescribed blood thinners such as COX-1 inhibitor aspirin and P2Y12 antagonist Plavix have a common problem: By decreasing platelet aggregation, they also increase the risk of uncontrolled bleeding. An experimental drug with a novel mechanism of action might be able to cut that bleeding risk, a small first-in-human study has found.
The new compound, called ACT017, was developed by French startup Acticor Biotech. In a phase 1 study on healthy volunteers, the drug showed it could inhibit clot formation without prolonging bleeding time, a marker that indicates increased risk of hemorrhage, according to results published in Arteriosclerosis, Thrombosis and Vascular Biology, an American Heart Association journal.
“There is a clear need for a novel antiplatelet agent that resolves platelet aggregation and clot formation without raising the risk for bleeding. Such a therapy would considerably improve and expand our current therapeutic arsenal for the treatment of acute stroke,” Martine Jandrot-Perrus, M.D., Ph.D., the study’s senior author and a consultant for Acticor, said in a statement.
Antiplatelets are often prescribed to help prevent the formation of blood clots, which can lead to cardiovascular diseases such as stroke. But using these popular drugs at the acute phase of ischemic stroke is linked to unacceptable hemorrhage, according to the study’s authors.
Enter ACT017. The drug is an antibody fragment that’s directed against a new target called platelet glycoprotein VI (GPVI). The protein is critical for blood clot formation but doesn’t affect the regulation of bleeding, making it an ideal target for safely inhibiting platelet clumps, the authors explained.
Previous studies in monkeys showed no adverse effect when ACT017 was given at the highest tested dose of 80 mg/kg. The use of a 6-hour intravenous infusion at 8 mg/kg induced prolonged inhibition of platelet aggregation.
In the phase 1 study, 36 healthy adult participants ages 22 to 65 were divided into six groups, and each group received intravenous infusions over six hours with various doses of the drug ranging from 62.5 mg to 2,000 mg. Each dosing cohort also had two more volunteers who received a placebo. The drug was well-tolerated at all doses, without serious side effects, while its therapeutic effect increased with the dose used, the investigators reported.
Scientists have been looking at different new approaches for improving the safety profile of blood thinners. A team at the Wyss Institute at Harvard University recently created “decoy” platelets that could reduce platelet binding, and their inhibition effect could be easily reversed by transfusing normal platelets, according to the researchers. Scientists from National Taiwan University have previously created one therapy based on snake venom that also targets GPVI.
Jandrot-Perrus and colleagues found the phase 1 results encouraging because of ACT017's safety profile. “Another encouraging finding is the fact that the drug's action on platelets is rapid, specific and largely reversible within 24 hours,” she said in the statement.
Last October, Acticor raised €15.3 million in series B with contribution from European and Asian investors. The biotech said the money will help finance the phase 2 study of ACT017, its lead candidate, in acute ischemic stroke.