Amag merges with Perosphere, adding NOAC antidote

Amag Pharma has struck a merger deal with Perosphere, adding an anticoagulant reversal agent in midstage trials to its emerging hematology business.

The terms of the deal see Amag making an upfront payment of $50 million for privately-held Perosphere, assuming $18.5 million of its debt and other liabilities, and committing to pay up to $365 million in regulatory and commercial milestones.

Reversal agent ciraparantag is being developed as an antidote to direct Factor Xa inhibitor-targeted novel oral anticoagulants (NOACs)—namely Bayer/Johnson & Johnson’s Xarelto, Pfizer/Bristol-Myers Squibb’s Eliquis and Daiichi Sankyo’s Savaysa—as well as low molecular weight heparin (LMWH) enoxaparin.

Collectively, these drugs make billions of dollars in sales worldwide and are used to treat around 6 million people in the U.S. and 9 million elsewhere for disease like atrial fibrillation, deep vein thrombosis and pulmonary embolism.

While these drugs have all shown their worth in treating thrombosis-related diseases, there is always a risk that their use can lead to uncontrolled bleeding, and in these cases reversal agents are needed to switch off their activity. It is estimated that up to 2% of patients treated with NOACs get bleeding complications.

In a phase 2b trial, ciraparantag at a dose of 200mg saw whole blood clotting time (WBCT) returned to normal within an hour of dosing for all four Factor Xa-acting drugs.

Perosphere says ciraparantag is different to current reversal agents—which at the moment consist of Portola’s AndexXa for Xarelto and Eliquis and Boehringer Ingelheim’s Praxbind for its alternative NOAC Pradaxa, which works as a thrombin inhibitor.

For a start, it’s a small-molecule drug that can be stored at room temperature and can be delivered in just 10 minutes. It also protects for more than 24 hours whereas AndexXa’s activity is for a couple of hours and works for all Factor Xa inhibitors.

Amag is also hoping the drug will avoid a warning of prothrombotic effects that appears on AndexXa’s label, and thinks its drug could be cheaper to produce.

Perosphere and Amag say they have now designed a phase 3 program that could start before the end of next year, setting up a possible filing and approval in 2021 if the combined company can win breakthrough drug designation from the FDA. Amag thinks ciraparantag could have peak sales potential of $500 million a year in the U.S. alone.

The merger is all about Perosphere’s lead agent, but Amag will also pick up a couple of preclinical programs, including a novel felbamate formulation in development for epilepsy and traumatic brain injury.

It’s another step towards diversification for the specialty pharma company, which is best known for its growing range of women’s health medicines but also sells Feraheme product for iron deficiency anemia.