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BioInvent Tumbles on Double Blow to ThromboGenics Deal

By Cormac Sheridan
Staff Writer

The strategic alliance between BioInvent International AB and ThromboGenics NV received a double whammy, as the two companies halted development of an anticoagulation antibody, TB-402, following unfavorable data from a Phase IIb head-to-head trial against Xarelto (rivaroxaban), while Roche Holding AG decided to exit a three-way alliance to develop an angiogenesis inhibitor, TB-403.

Lund, Sweden-based antibody developer BioInvent took a severe hammering when the news was disclosed Tuesday.

Shares in the company (STOCKHOLM:BINV) hit a 52-week low, closing at SEK4.75 (US66 cents), a drop of 63 percent.

Buoyed by the progress of its ophthalmology drug ocriplasmin, which is under regulatory review in Europe and the U.S., Leuven, Belgium-based ThromboGenics was less severely affected. However, its stock (BRUSSELS:THR) was still off almost 16 percent by midafternoon, closing Tuesday at €19.47 (US$24.26), down 10 percent.

In terms of efficacy, TB-402, a long-acting anticoagulant targeting Factor VIII, achieved a similar outcome to Xarelto, an oral coagulant targeting Factor Xa, which is marketed by Leverkusen, Germany-based Bayer AG.

The trial, which recruited 632 patients undergoing hip replacement surgery, compared the effect of the two drugs on the prevention of venous thromboembolism (VTE; blood clot formation). Of those who received a single intravenous infusion of TB-402, 5.3 percent experienced VTE (a pooled result from high- and low-dose arms) vs. 4.7 percent of those who received a once-daily dose of Xarelto for 35 days.

However, 6.5 percent of those on TB-402 experienced a major or clinically relevant bleeding event, vs. 1.4 percent of those on Xarelto, a statistically significant result.

"If you want to play in this market, [you must] at least be as good as the market leader," ThromboGenics CEO Patrik De Haes told BioWorld International. "The worst thing that could have happened is if we'd achieved an 'iffy' result."

The program has received €20 million in investments. The decision to halt it now is at least based on solid evidence. "The result can be painful, but the diagnosis is correct," De Haes said. "The treatment is easy. Stop spending money on it."

TB-403, in contrast, is by no means dead, but it does appear to be a victim of portfolio prioritization within Basel, Switzerland-based Roche. "Prioritization is on the agenda every day," BioInvent CEO Svein Mathisen told BioWorld International.

The Roche decision was not a surprise to Jan De Kerpel, analyst at KBC Securities in Brussels. "The development of the product in the hands of Roche has been very slow, especially because there was internally in Roche a big debate between the former Genentech researchers (who developed Avastin) and the Roche researchers who in-licensed TB-402 back in 2009," he wrote in a research note.

Moreover, oncology was Roche's sole focus on the drug, which targets placental growth factor, De Haes said. "In oncology, they always studied it in combination with Avastin (bevacizumab)," he said.

ThromboGenics and BioInvent continue to believe the drug has potential in oncology and in other areas, including ophthalmology and liver disease.

"We will first look at the rationale in these indications before we discuss the commercial strategy," BioInvent's Mathisen said.

Costs for the TB-403 program are shared on a 50-50 basis, but the returns are split 60-40 in favor of ThromboGenics, which invented the treatment concept. That company remains firmly committed to it. "We are definitely interested in investing in TB-403," De Haes said.

The company, moreover, is flush with cash, having reported €127 million as of March 31 and having grossed another €77.8 million in a private placement shortly afterward. It received another €90 million in near-term milestones arising out of its €375 million alliance with Alcon Inc. on ocriplasmin.

ThromboGenics is not opposed to spending some of its cash balance on buying out its partner's interest in the program. "We would not be unhappy if we could acquire the [full rights to] the project," he said.

BioInvent reported SEK104.8 million as of March 31 and grossed another SEK138 million in a preferential rights issue shortly afterward, enough to take the company through 2013, Mathisen said.

Apart from TB-403, BioInvent has two other clinical stage programs, each of which is reporting data later this year. BI-204, which is in a Phase II trial in patients with atherosclerosis, targets a low density lipoprotein called apoB100 and is partnered with Genentech. BI-505, which targets the adhesion protein ICAM-1 (CD54), is undergoing a Phase I trial in multiple myeloma.