Portola Enters into Clinical Collaboration Agreement with Bayer and Janssen for Phase 2 Study of Universal Factor Xa Inhibitor Antidote, PRT4445, and Xarelto
SOUTH SAN FRANCISCO, Calif. (February 5, 2013) – Portola Pharmaceuticals, Inc. today announced a clinical collaboration agreement with Bayer HealthCare and Janssen Pharmaceuticals, Inc. for a Phase 2 study evaluating the safety and effectiveness of PRT4445, Portola’s universal antidote for Factor Xa inhibitors, in healthy volunteers who have been administered the U.S. Food and Drug Administration-approved oral Factor Xa inhibitor XARELTO® (rivaroxaban). PRT4445 is designed to reverse the anticoagulant activity of Factor Xa inhibitors in patients experiencing an uncontrolled bleeding episode or requiring emergency surgery. There are no currently approved agents to reverse the activity of oral Factor Xa inhibitors, and PRT4445 is the only universal Factor Xa inhibitor antidote in clinical development.
The collaboration will be in effect throughout the Phase 2 study, which is scheduled to be completed in the second half of 2013. The study is designed to demonstrate the safety of PRT4445 at several different doses and its ability to reverse the anticoagulant activity of XARELTO. Bayer and Janssen will make an undisclosed cash payment to Portola and will provide development and regulatory guidance for the study. Portola retains all global development and commercialization rights for PRT4445.
“Oral Factor Xa inhibitors are a major advance over standard therapies such as warfarin and enoxaparin, but there is an important unmet medical need for an antidote to help manage patients if they require their anticoagulant to be reversed,” said William Lis, chief executive officer of Portola. “Our goal is to accelerate the development and regulatory approval of PRT4445 as the first universal reversal agent for all Factor Xa inhibitors. We are pleased to be working with our Bayer and Janssen colleagues to help achieve this objective with XARELTO.”
Clinical trial results suggest that, annually, between 1-4 percent of patients treated with Factor Xa inhibitors will experience uncontrolled bleeding, and an additional 1 percent will require emergency surgery, depending on the patient’s underlying medical condition. Currently, standard clinical measures are employed to manage these events. Development of an agent specifically designed to reverse the activity of Factor Xa inhibitors may provide an important treatment option for patients who experience an uncontrolled major bleeding event or require emergency surgery.
PRT4445 is a novel recombinant protein designed to reverse the anticoagulant activity in Factor Xa inhibitor-treated patients suffering from an uncontrolled bleeding episode or undergoing emergency surgery. It is similar to native Factor Xa but has structural modifications intended to restrict its biological activity to reverse the effects of Factor Xa inhibitors. PRT4445 works by acting as a decoy for Factor Xa inhibitors in the blood, thereby preventing them from inhibiting the activity of native Factor Xa. As a
result, the native Factor Xa is available to participate in the coagulation process and restore normal clotting.
Results of a Phase 1 single ascending dose safety and tolerability study, conducted by Portola in 32 healthy volunteers in the United States, showed that PRT4445 was generally well tolerated with no apparent safety signals.
About XARELTO® (rivaroxaban) XARELTO works by blocking the blood clotting enzyme Factor Xa. XARELTO does not require routine blood monitoring and is approved for six distinct uses:
1. To reduce the risk of blood clots in the legs and lungs of people who have just had knee replacement surgery.
2. To reduce the risk of blood clots in the legs and lungs of people who have just had hip replacement surgery.
3. To reduce the risk of both hemorrhagic and thrombotic strokes as well as other blood clots in people with atrial fibrillation not caused by a heart valve problem. There is limited information on how XARELTO® compares to a medicine called warfarin in reducing the risk of stroke when the effects of warfarin are well controlled.
4. To treat people with pulmonary embolism (PE).
5. To treat people with deep vein thrombosis (DVT).
6. To reduce the risk of recurrence of DVT or PE following an initial six months of treatment for acute venous thromboembolism.
The extensive program of clinical trials evaluating rivaroxaban makes the compound the most studied oral Factor Xa inhibitor in the world today. By the time of its completion, more than 100,000 patients will have participated in the rivaroxaban clinical development program. There are two additional indications currently submitted and under review at the FDA.
About Portola Pharmaceuticals, Inc.
Portola Pharmaceuticals is a biopharmaceutical company focused on developing and commercializing novel therapeutics in the areas of thrombosis, other hematologic disorders and inflammation for patients that currently have limited or no approved treatments. In thrombosis, Portola is developing betrixaban, a novel, oral, once-daily inhibitor of Factor Xa in development for extended duration prophylaxis of venous thromboembolism (VTE) in acute medically ill patients; and PRT4445, a universal antidote for Factor Xa inhibitors. Portola has a clinical collaboration agreement with Bristol-Myers Squibb and Pfizer for the initial Phase 2 proof-of-concept study of PRT4445 in combination with ELIQUIS® (apixaban). Portola retains full commercial rights for PRT4445.
Portola’s two other product candidates are orally available kinase inhibitors with unique pharmacologic properties targeting hematologic cancers and inflammatory disorders: PRT2070, which inhibits both spleen tyrosine kinase (Syk) and Janus kinases (JAK) enzymes, which regulate important signaling pathways; and PRT2607, which selectively inhibits Syk. Portola is developing PRT2070 for treatment of certain B-cell hematologic cancers, with a particular focus on patients who have mutations that cause failure or relapse with existing treatments and those in development. Portola has a collaboration agreement with Biogen Idec to develop specific inhibitors of Syk, including PRT2607. For more information, visit www.portola.com.
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Mardi Dier Paul Laland
CFO, Portola Pharmaceuticals BrewLife
Posted: February 2013
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