LONDON – Profibrix NV announced positive results in the Phase III trial of Fibrocaps in promoting blood clotting during surgery, triggering the company's acquisition under a pre-arranged deal in which The Medicines Co. has purchased all the outstanding equity for $90 million and will pay up to $140 million on U.S. and European regulatory and sales milestones.

The payment is in addition to $10 million paid by Medicines to secure the option to acquire Profibrix.

The Finish-3 Phase III trial of Fibrocaps, a dry powder topical formulation of fibrinogen and thrombin, met all the primary and secondary endpoints in four different kinds of surgery. The results of the trial, carried out at 65 sites in the U.S. and Europe, will now form the basis of submissions for marketing approvals to the FDA and the European Medicines Agency.

Medicines, of Parsippany, N.J., made the agreement to purchase Profibrix in June, pending review of the results of the Finish-3 trial. Clive Meanwell, chairman and chief executive, said Fibrocaps will be complementary to Medicines' recombinant thrombin product, Recothrom.

Profibrix, of Leiden, the Netherlands, will be integrated into the Recothrom team, with the Leiden site becoming the center for hemostasis of the combined company.

The acquisition will reunite Profibrix CEO Jan Öhrström with Recothrom, a product he steered to market when he was chief medical officer of Zymogenetics Inc., of Seattle. It will also reunite him with former colleagues in Seattle. "On a personal note, in my days at Zymogenetics, I had the vision of building a cutting-edge surgical hemostasis franchise," Öhrström said.

On the commercial front, Profibrix is "a natural fit" with Medicines. "I can explain this to my mum and dad, and when you can explain things like that, it makes strategic M&A very much easier," Öhrström told BioWorld International.

The main venture capital investors in Profibrix, Vesalius Biocapita, INKEF Capital, Index Ventures and Gilde Healthcare Partners, have put about $40 million into the company since its formation in 2004. In addition, Profibrix has raised capital from government loans.

While Fibrocaps is derived from donated human plasma, Profibrix also has a recombinant fibrinogen program and currently is working with a GMP manufacturer to scale up production to industrial volumes.

Meanwell said the combination of the recombinant version of fibrinogen with Recothrom, "potentially allows us to create the world's first recombinant thrombin and fibrinogen products."

Most biotechs could scarcely dream of the speed with which Profibrix has managed to turn around the 719-patient Phase III trial, which got under way a little more than a year ago. The aim was to replicate Phase II results in which clotting occurred at two minutes compared to 4.8 minutes with the comparator product. The Phase III trial covered spinal, liver, vascular and soft-tissue surgery, with the aim of getting a broad label covering a large swathe of the $1 billion-plus U.S. topical hemostasis market.

"Phase III replicated Phase II in all senses. We expanded the study and made sure we had four distinctly different surgical indications and covered all the bases for regulatory submission. We came out with very attractive data, showing very significant superiority over gelatin sponge, and the [Fibrocaps] clotting time generally came out at less than two minutes," Öhrström said.

It is expected that the file will be submitted in Europe toward the end of 2013 and in the U.S. at the start of 2014. While in the U.S. Fibrocaps will slot into the existing Recothrom sales infrastructure, that capability will have to be built up in Europe.

That will also create the opportunity to file for approval of Recothrom in Europe, though Öhrström said that as yet there is no definite plan on how and when this will happen.

Fibrocaps is produced by a contract manufacturer, Novolabs, in Leicester, UK, and Öhrström said the company will be the main global supplier of marketed product for the foreseeable future.

Formulating the two blood-clotting proteins fibrinogen and thrombin as a dry powder allows them to be encapsulated in the same vial and to be activated simultaneously, as soon as the powder is wetted by blood in a wound. On activation, thrombin converts fibrinogen to fibrin, the fibrous protein matrix of blood clots.

In addition to faster clotting time, Fibrocaps has the advantage over liquid sealants and other hemostasis products that it is ready for immediate use and is stable at ambient temperatures. The particle size of Fibrocaps is similar to inhaled asthma products, and Profibrix has developed a dry-power delivery device for the precise application of the hemostasis agent.