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Portola in the News

BioWorld Today
November 22, 2011
By Mari Serebrov

Having raised $89 million in its latest financing round, Portola Pharmaceuticals Inc. is preparing to fly solo on its pivotal Phase III trial that will evaluate betrixaban in the prevention of pulmonary embolisms.

The Series D financing, a preferred stock offering, raised more than the South San Francisco-based biotech had expected, Portola’s Chief Financial Officer Mardi Dier told BioWorld Today. The round also broadened the company’s international investment base. Besides existing investors, Temasek, an Asia investment company, and Eastern Capital Ltd. came on board.

Combined with the cash the company has on hand and its recent multi-million-dollar deal with Biogen Idec, the $89 million financing should be enough to fuel betrixaban, a once-daily, oral Factor Xa inhibitor, through to approval, Dier said. The pivotal trial is expected to begin in the first half of next year. (See BioWorld Today, Oct. 28, 2011.)

Originally Merck and Co. Inc. was set to do the pivotal test flight for the oral Factor Xa inhibitor, but it bailed earlier this year after reprioritizing its late-stage investigational drugs. Now that Portola is back in the pilot’s seat, it’s plotting a different flight plan. (See BioWorld Today, March 25, 2011.)

While oral anticoagulants like betrixaban can address a number of indications, Merck was focused on strokes. Betrixaban has promise in that area. The Phase IIa EXPLOREXa study showed a once-daily dose reduced the incidence of major and clinically relevant nonmajor bleeds in patients with nonvalvular atrial fibrillation or atrial flutter and at least one risk factor for stroke compared with dose-adjusted warfarin.

But the stroke space has generated some traffic. Two novel agents have been approved in the past 12 to 18 months, Portola CEO Bill Lis told BioWorld Today. One of those is Boehringer Ingelheim GmbH’s Factor IIa inhibitor Pradaxa (dabigatran etexilate), which was approved last month for stroke risk reduction in patients with nonvalvular atrial fibrillation. And other big pharma companies have products in development to treat or prevent stroke.

As a small biotech flying solo, Portola is interested in an indication with clearer skies. So it’s changing course, hoping to become the first oral Factor Xa inhibitor to the market for both hospital and post-discharge prevention of pulmonary embolism (PE) in acute medically ill patients.

At least three injectables have been approved for hospital PE prevention, Lis said, but no drugs have been approved for post-discharge. Yet PE remains a risk for up to 30 days, and possibly up to 90 days, following discharge. Despite the lack of approvals, it’s not an uncharted path for an oral anticoagulant. Apixaban (Bristol-Myers Squibb, Pfzer) and rivaroxaban (Xarelto/Bayer, Johnson & Johnson) have been tested for the indication. While the ADOPT and MAGELLAN trials were valuable in pointing the way forward for oral anticoagulants, they didn’t produce the results needed to get FDA approval, Lis said.

Xarelto has been approved overseas for acute postsurgical deep vein thrombosis prevention, but it received a complete response letter from the FDA in 2009. And data presented at this year’s American Heart Association’s Scientific Sessions showed a 30-day course of apixaban as a thrombosis prophylaxis was not superior to a shorter course of subcutaneous enoxaparin.

Portola’s flight plan for betrixaban is similar to that of other oral anticoagulants tested in the thrombosis area. It consists of a single, global trial enrolling about 6,000 subjects. But Lis expects greater success because of betrixaban’s unique properties—such as a half-life suitable for once daily dosing, a low level of clearance through the kidney and lack of metabolism through the CYP pathway.

If betrixaban succeeds, the approval will be transformational for Portola, Lis said. Not only would it be the biotech’s first approval, it would come in a multi-billion dollar indication that affects more than 20 million patients globally.

Since the drug would be used or prescribed in the hospital setting, the launch and marketing efforts would be doable for the small biotech, Lis said. But Portola is still open to finding partners to help market the drug.

Besides advancing betrixaban, Portola’s Series D financing will go a long way in developing a companion product, PRT064445, a recombinant Factor Xa inhibitor antidote that reverses the No. 1 limitation of anticoagulants—life-threatening bleeds. While being developed as an antidote to betrixaban, PRT064445 is designed to treat a drug-induced major bleed regardless of what Factor Xa inhibitor is involved.

The antidote will enter Phase I early next year. PRT064445 is intended for a hospital setting for patients with life-threatening bleeds or in advance of surgery for patients on anticoagulants.

Based on its uniqueness and the growing unmet need to reverse major bleeds, Lis anticipates PRT064445 will be developed on an accelerated path. Portola is in discussions with the FDA to expedite the pivotal trial.