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Cardiorentis' Heart Failure Trial Backed by $131M Investment


By Nuala Moran
Staff Writer

LONDON – The secretive backers of Cardiorentis Ltd. prefer to remain anonymous, but they obviously are expecting to see the name of the company's main asset, Ularitide, in lights, having made a €100 million (US$130.6 million) investment to put the product through a Phase III trial in treating 2,116 patients with acute heart failure.

The man steering that effort is Elmar Schnee, former board member of Merck KGaA, who was appointed chairman and CEO of Cardiorentis in October 2011, following its formation in January 2010 from predecessor Cardiopep GmbH.

"Cardiopep had a great asset, but it couldn't afford to develop it," Schnee said. "The investors behind Cardiorentis are private individuals who don't want to disclose their names. They have put in €100 million to buy the asset and complete the Phase III trial of Ularitide," he told BioWorld Today.

Schnee said he believes the timing of the Phase III trial of Ularitide could not be better, coming as another front-running drug in development for the treatment of acute heart failure, Novartis AG's serelaxin (RLX030), delivered mixed Phase III data. That drug, which is a synthetic version of the hormone relaxin, met one co-primary endpoint but failed to hit the other and also missed the secondary endpoints.

Those less-than-resounding results followed the publication in July 2011 of the largest study on another treatment for acute heart failure, Johnson & Johnson's Natrecor (nesiritide). That 7,000-patient trial indicated that the drug, a recombinant form of human B-type natriuretic peptide, was not as effective as the clinical trial that formed the basis for its approval in 2001 had indicated.

In common with Natrecor, Ularitide is a version of a natriuretic peptide, in this case, a synthesized form of urodilatin, which is produced in the kidneys. Cardiorentis said Ularitide has broad systemic effects as a vasodilatory agent when infused into the circulation.

Schnee said the product has a "triple action," and is potent and finely targeted, binding selectively in the cardiovascular system. The main pharmacological effects are vasodilation of renal, pulmonary and coronary arteries; diuresis and natriuresis; and inhibition of the renin-angiotensin-aldosterone system. In animal models, ularitide increased urine flow and sodium excretion and improved hemodynamic variables, according to Cardiorentis.

The TRUE-AHF Phase III trial of Ularitide is testing the drug in addition to conventional therapy. Schnee said the endpoint is a composite of measures, including patients' own ratings of the effect on the dyspnea (breathlessness) that is the hallmark of acute heart failure, while physicians' ratings will be on the basis of other treatments needed in addition to Ularitide, such as more diuretics or mechanical ventilation.

"Our hypothesis is that Ularitide improves symptoms much faster [than alternative drugs] and reduces the use of additional medications," Schnee said. Other measures to be factored into the analysis are length of hospital stays, readmissions and mortality. Schnee noted that since there are no other compounds currently in Phase III development for acute heart failure, recruitment should be speedy, and it is hoped the trial will complete in mid-2014.

Meanwhile, despite the mixed data, Novartis said it will talk to regulators about the way forward for serelaxin. The Phase III results unveiled at last month's American Heart Association meeting in Los Angeles and published in The Lancet, showed a significant benefit from serelaxin up to day five (p = 0.0075) in improving dyspnea. However, the other co-primary endpoint of relief of dyspnea at six hours, 12 hours and 24 hours post-administration did not reach significance.

Novartis said because one of the primary endpoints was met, the study was positive according to protocol criteria.

The trial also did not meet its secondary efficacy endpoints of days alive and out of hospital up to day 60 (p = 0.37), and cardiovascular death or re-hospitalization due to heart or kidney failure up to day 60 (p = 0.89).

However, overall, serelaxin did show a reduction of 37 percent in mortality from any cause compared to placebo at six months.

Novartis acquired serelaxin three years ago through the purchase of San Mateo, Calif.-based Corthera Inc., to add to its Diovan (valsartan) heart failure franchise. (See BioWorld Today, Dec. 29, 2009.)

The discovery of Ularitide was made by Wolf-Georg Forssmann at the Lower Saxony Institute for Peptide Research in Germany, a former publicly funded body that was privatized in 2000 as the Pharis Group. Cardiopep operated as a subsidiary of Pharis until the acquisition by Zug, Switzerland-based Cardiorentis in 2010. Forssman is a vice president of Cardiorentis.

Ularitide also is suitable for treating renal insufficiency, pulmonary hypertension and acute bronchoconstriction caused by asthma, and Schnee said the compound has been administered to 5,500 patients on a compassionate-use basis. While the backers are "very focused" on developing Ularitide in acute heart failure, there is exploratory work in progress to generate more data as the basis of new programs in other indications.

Cardiorentis has not plotted a precise route forward to commercialization if it gets the data needed in Phase III. Schnee said it could do a mixture of out-licensing and building its own franchise in particular markets, find a single partner and devote itself to new research, or go for an outright sale. "We will decide when we have the results," he said. "Acute heart failure is a great opportunity: in Europe, there is no single drug that says for treating acute failure on the label."