Data from two Phase 2 randomized, placebo-controlled, dose-ranging studies using ciraparantag demonstrate efficacy and safety in the reversal of apixaban and rivaroxaban
WALTHAM, Mass., July 12, 2020 — AMAG Pharmaceuticals, Inc. (NASDAQ: AMAG) today announced the poster presentation of data from two Phase 2 randomized, placebo-controlled, dose ranging studies which showed safety and efficacy of ciraparantag reversing the effects of apixaban and rivaroxaban in healthy adults age 50-75 years. The poster, “Efficacy and Safety of Ciraparantag in Reversing Apixaban and Rivaroxaban in Healthy Adults” was accepted for the 2020 International Society on Thrombosis and Haemostasis (ISTH) virtual annual meeting. Ciraparantag is in development for use in patients treated with direct oral anticoagulants (DOACs) and low molecular weight heparin (LMWH) when reversal of the anticoagulant effect of these products is needed for emergency surgery, urgent procedures or due to life-threatening or uncontrolled bleeding.
Results from both studies, which randomized a total of 113 subjects, showed that steady-state anticoagulation induced by apixaban or rivaroxaban was reversed by a single IV infusion of ciraparantag in a dose-related manner as assessed by whole blood clotting time (WBCT). WBCT is a direct measure of anticoagulation/hemostasis and a global measure of clotting. Mean WBCT values in the ciraparantag groups decreased toward baseline 15 minutes after dosing, versus placebo which took five hours commensurate with the decline of anticoagulant drug concentration. For reversal, defined as achieving a WBCT ≤10% above baseline within one hour after dosing and subsequently sustained through at least five hours, this response was achieved in 100 percent of subjects receiving ciraparantag doses ≥60 mg for reversal of apixaban, and 100 percent of subjects receiving ciraparantag doses of 180 mg for reversal of rivaroxaban. Ciraparantag was well tolerated at all doses evaluated in these studies. The most frequent adverse events associated with ciraparantag were mild, transient sensations of warmth or flushing, which were observed more frequently with higher doses of ciraparantag.
“DOACs have become the dominant means for chronic anticoagulation, and there remains a need for an effective reversal agent with broad activity that can be administered quickly and conveniently for patients with serious uncontrolled bleeding or those who require emergency surgery,” said Dr. Jack Ansell, Professor of Medicine, Hofstra Northwell School of Medicine. “These data are encouraging as they demonstrate a ciraparantag dose response for reversal of apixaban and rivaroxaban which, along with the safety findings, will inform dose selection for future studies.”
In the two studies, adult subjects were treated with apixaban or rivaroxaban and those who reached steady-state anticoagulation were randomized within each dose cohort in a 3:1 ratio to receive ciraparantag or placebo, which was administered three or four hours after last dose of the anticoagulant. Ciraparantag was administered as a single intravenous infusion over 10 minutes, followed by serial testing of WBCT over 24 hours. Doses of ciraparantag were evaluated at 30 mg, 60 mg and 120 mg for apixaban and 30 mg, 60 mg, 120 mg and 180 mg for rivaroxaban.
Ciraparantag is a novel small, water-soluble molecule being investigated for reversal of anticoagulation induced by direct oral anticoagulants (DOACs) or low molecular weight heparin (LMWH). Target patient populations include patients for whom rapid reversal of anticoagulation is needed because of life-threatening or uncontrolled bleeding, or for emergency surgery or urgent procedures. It is believed that ciraparantag exerts its effects by binding to and blocking the effects of DOACs such as Xarelto® (rivaroxaban), Eliquis® (apixaban) and Savaysa® (edoxaban), as well as to the LMWH Lovenox® (enoxaparin sodium injection), which in turn reestablishes normal clot formation. Ciraparantag is administered by intravenous infusion; the anticipated clinical treatment regimen is a single dose administered over approximately 10 minutes. Ciraparantag has been studied across seven completed trials, with 277 subjects having been dosed with ciraparantag and has been well tolerated in these studies. To date, the most common adverse events related to ciraparantag have been mild transient sensations of warmth or skin flushing, skin tingling, and alterations in taste.
AMAG is a commercial stage biopharmaceutical company focused on bringing innovative products to patients with unmet medical needs. The company does this by leveraging its development and commercial expertise to invest in and grow its pharmaceutical products across a range of therapeutic areas. For additional company information, please visit www.amagpharma.com.
Forward Looking Statements
This press release contains forward-looking information about AMAG Pharmaceuticals, Inc. within the meaning of the Private Securities Litigation Reform Act of 1995 and other federal securities laws. Any statements contained herein which do not describe historical facts, including, among others, AMAG’s beliefs about the mechanism of action of ciraparantag and statements about ciraparantag, including the safety and efficacy, anticipated target patient population and dosing regimen for ciraparantag are based on management’s current expectations and beliefs and are forward-looking statements which involve risks and uncertainties that could cause actual results to differ materially from those discussed in such forward-looking statements.
Such risks and uncertainties include, among others, the risk that ciraparantag is not approved as a reversal agent for a broad spectrum of anticoagulants, as well as those risks identified in AMAG’s filings with the U.S. Securities and Exchange Commission (SEC), including its Annual Report on Form 10-K for the year ended December 31, 2019, its Current Reports on Form 8-K, its Quarterly Reports on Form 10-Q, including for the quarter ended March 31, 2020, and in any subsequent filings with the SEC , which are available at the SEC’s website at www.sec.gov. Any such risks and uncertainties could materially and adversely affect AMAG’s results of operations, its profitability and its cash flows, which would, in turn, have a significant and adverse impact on AMAG’s stock price. AMAG cautions you not to place undue reliance on any forward-looking statements, which speak only as of the date they are made.
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