In early 2003, when Johnson & Johnson bought Scios Corp. for $2.4 billion in cash, the most talked-about drivers of the deal were Natrecor (nesiritide), Scios' approved drug for congestive heart failure; an arthritis drug in the works, SCIO-469; and the p38 MAP kinase inhibitor program.
But, as J&J knew well, there was another, underlying asset with strong value: Scios' Acute Decompensated Heart Failure National Registry, known as ADHERE, the largest such marker-finding database in the world. The following year, Scios reported finding clinical indicators (levels of blood urea nitrogen and serum creatinine, along with systolic blood pressure) that might be used to predict mortality risk. A collection of knowledge like ADHERE not only lets doctors search, compare and prescribe more wisely, but provides an important potential leg up in designing clinical trials.
Last week's news of the Swiss firm Actelion Ltd.'s plan to buy out CoTherix Inc., of Brisbane, Calif. - which gives Actelion the inhaled therapy for pulmonary arterial hypertension (PAH), Ventavis - had an element of underlying déj vu. CoTherix owns a tracking database, too: REVEAL, which stands for the Registry to Evaluate Early And Long-term PAH disease management.
REVEAL, which started enrolling patients at the end of March, will stop at the end of 2007, aiming to get about 3,000 patients at 50 sites, who will be followed for five years. To qualify, patients must fall into the category of Class I under guidelines set by the World Health Organization, and may be newly diagnosed with PAH or previously diagnosed by way of right-heart catheterization.
The registry will let overseers put together data from PAH patients treated with varying approaches, providing benefits similar to Scios' ADHERE, and in an indication that's growing more and more competitive.
Jean-Paul Clozel, CEO and founder of Actelion, told investors during a conference call regarding the CoTherix takeover that both companies continue to invest in improving PAH care and are exploring Tracleer further "in different PAH situations and in combination with other drugs."
Other, smaller PAH registries have included the National Institutes of Health library, with 187 patients followed from 1981 to 1985. A French National Registry was established in 2000, enrolling 674 patients from 2002 to 2003, with a goal of updating the data gained through the NIH effort.
In the CoTherix takeover, for $13.50 per share, or about $420 million (a 21 percent premium over the Nov. 17 closing price), Actelion also gets fasudil, a rho-kinase inhibitor for PAH that CoTherix licensed earlier this year in North America and Europe from Asahi Kasei Pharma Corp. for an up-front fee of $8.75 million, plus milestone payments and royalties on future products. CoTherix also acquired exclusive rights to fasudil for stable angina in the same territories, and the deal carries an option - soon to belong to Actelion - to develop the compound in North America and Europe for other potential indications using the licensed formulations, except for stroke and eye diseases.
An open-label, Phase IIa dose-ranging study with the extended-release version as a monotherapy in treatment-na ve patients is expected in the first half of 2007, possibly in Europe (since many patients already are being treated in the U.S.), although that's not a sure thing, as physicians in the U.S. also have shown enthusiasm about the drug's prospects. In the first half of next year, a North American Phase II dose-ranging trial of oral fasudil ER in stable angina is due to start, with a Phase II study testing inhaled fasudil against PAH in the second half.
Oral and intravenous fasudil were in-licensed by Schering AG in 2002, but Schering gave the drug back to Asahi two years later when the Berlin-based firm divested most of its cardiovascular portfolio. CoTherix already was looking into fasudil when Schering had the compound, and once the rights transferred back to Asahi, Schering introduced CoTherix officials to Asahi leaders.
CoTherix's Ventavis (iloprost), a prostacyclin that was cleared in the U.S. at the end of 2004, is expected to sell between $60 million and $70 million this year. Earlier this year, CoTherix boosted the price by about 10 percent, making the cost of a year's treatment about $71,000.
Ventavis could add $100 million U.S. dollars to top-line revenues in 2007, Clozel said, and the combined company after the takeover expects to have five compounds in Phase III trials that year.
"CoTherix has [done] a fantastic job to have this drug registered in the U.S. with a good label in record time," he said. "They have also put in place a strong scientific program and an excellent sales force."
Previously known as Exhale Therapeutics Inc., CoTherix was founded in 2000 and lately has been dogged by concerns over United Therapeutics Corp.'s Remodulin (treprostinil), for which UTC has a licensing deal with specialty pharma firm Supernus Pharmaceuticals Inc. to develop an oral version. Actelion's own endothelin agonist, Tracleer (bosentan), a leader among PAH drugs, also faces a threat from Phase III compound ambrisentan, which Gilead Sciences Inc. acquired through its recently completed $2.5 billion buyout of Denver-based Myogen Inc.
Tracleer won approval in Europe four years ago and in the U.S. in November 2001. Another PAH player is Revatio, from Pfizer Inc., a lower-dose form of sildenafil citrate (the active ingredient in the blockbuster erectile-dysfunction drug Viagra), that was cleared for PAH a year ago. Researchers believe using a PDE5 inhibitor such as sildenafil with a prostacyclin will work even better against PAH than Tracleer when used with a prostacyclin.
Patients who fail Tracleer often are switched to Revatio or Ventavis, but sales forces would also like to see doctors give up GlaxoSmithKline plc's Flolan (epoprostenol) in favor of another compound.
The Actelion takeover has been given blessings by the boards of both companies and is expected to finish in the first quarter of next year.