ACC: After acing early trial, PhaseBio pushes forward with Brilinta-reversing drug

PhaseBio got a boost this weekend after unveiling phase 1 data for its Brilinta (ticagrelor) reversal agent in the New England Journal of Medicine and at the annual meeting of the American College of Cardiology. The 64-patient study, presented Sunday, showed that the drug quickly reversed the antiplatelet effects of Brilinta without causing serious side effects.

PhaseBio’s stock price jumped as much as 88% to $7.02 Monday morning before settling at $6.32 at the end of the day, a hike of about 67% over its price at the close of last week. The company, which is based in Malvern, Pennsylvania, and San Diego, priced its IPO at $5.00 per share in October, raising about $46 million in the deal, but it has been trading below that since mid-November. 

PhaseBio licensed the asset, dubbed PB2452, from AstraZeneca, which makes Brilinta, in 2017. It is an antibody fragment that counters the effects of Brilinta by binding the drug and its active metabolite. It would be used in situations where the clot-busting effects of Brilinta would need to be quickly reversed: in Brilinta patients who need urgent surgery, or who are experiencing major bleeding. 

There is currently no “effective method” to reverse Brilinta’s antiplatelet effects, “which increases the risk of spontaneous major bleeding,” Deepak Bhatt, M.D., M.P.H., who presented the study at ACC, said. Bhatt is the executive director of Interventional Cardiovascular Programs at Brigham and Women’s Hospital and a professor at Harvard Medical School. 

RELATED: PhaseBio nets $34M to advance Brilinta reversal agent, PAH drug 

The phase 1 study involved 64 healthy volunteers, 48 of whom received PB2452 and 16 of whom were given placebo. Those on PB2452 were split into 10 dosage groups: three groups received low doses of PB2452 or placebo without Brilinta, while the rest of the groups received higher doses after being given Brilinta for 48 hours. The study tested 30-minute infusions of 1-g, 3-g and 9-g doses of PB2452, as well as “various infusion regimens” of an 18-g fixed dose. 

It took five minutes for PB2452 to reverse Brilinta’s effects and the reversal lasted for more than 20 hours, according to the study. The investigators found “no evidence of a rebound in platelet activity after drug cessation.” 

“We are encouraged by the clinically meaningful results from the phase 1 trial, which demonstrate the potential of PB2452 to provide immediate and sustained reversal of ticagrelor antiplatelet activity,” John Lee, M.D., Ph.D., PhaseBio’s chief medical officer, said in a statement. “Furthermore, PB2452 exhibited a very favorable safety profile in healthy volunteers. … We look forward to initiating a phase 2a trial of PB2452 in the first half of this year and continuing to evaluate PB2452 as the first reversal agent for ticagrelor.” 

PhaseBio is planning to start a phase 2b study by the end of the year. It also has a second asset in its pipeline, PB1046, a treatment for pulmonary arterial hypertension that it developed in-house. The drug, an analog of vasoactive intestinal peptide (VIP), is based on elastin-like polypeptide technology licensed from Duke University. Native VIP has a half-life of less than a minute, while PB1046 has a half-life of 60 hours, making it suitable for once-weekly injection.