CoTherix Inc.'s late-June deal with Asahi Kasei Pharma Corp. to develop and sell inhaled fasudil, the rho kinase inhibitor for pulmonary arterial hypertension, only brought $8.75 million up front for the overseas firm, but it landed PAH back in the headlines yet again.
Calling fasudil a "terrifically potent" compound for reducing vasoconstriction, as well as cell proliferation, CoTherix's CEO Donald Santel told BioWorld Financial Watch the company plans to evaluate an extended-release, twice-daily formulation of fasudil and an inhaled version against PAH, with a pharmacokinetic study of fasudil ER slated for this year.
An open-label, Phase IIa dose-ranging study with the ER 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. are enthusiastic about the drug's prospects, Santel said.
In the first half of next year, the company aims to start a North American Phase II dose-ranging trial of oral fasudil ER in stable angina, 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. Santel said CoTherix already was sniffing around fasudil when Schering had the compound, and once the rights transferred back to Asahi, Schering introduced CoTherix officials to Asahi leaders. Hence the deal, which brings milestone payments and royalties on future products for Asahi.
The arrangement also includes an option for CoTherix to develop fasudil in North America and Europe for other indications using the licensed formulations, with the exception of stroke and eye diseases. An intravenous version of the compound was approved in June 1995 in Japan, and Asahi markets the drug (through Eisai Co. Ltd.) for prevention of cerebral vasospasm in patients with subarachnoid hemorrhage.
In PAH, CoTherix already has Ventavis (iloprost), an inhaled prostacyclin that was cleared in the U.S. at the end of 2004. Sales are expected to range between $60 million and $70 million this year. The company recently increased the price by about 10 percent, making the cost of a year's treatment about $71,000.
Analyst Mark Monane at Needham & Co. wrote in a research note that the fasudil deal "signals that CoTherix is building a pipeline," though developing the drug will take "significant time." He projected market launch at around 2010.
"We also note that developmental expenses will increase substantially, delaying profitability, likely until 2009," Monane wrote. "We place our model under review as we await further financial guidance." The composition-of-matter patent for fasudil expires in 2016, with the ER version's patent giving way three years later.
Andrew Fein, with C.E. Unterberg, Towbin, was even more sanguine about the Asahi pact. "For the first time in awhile, investors now have the second leg that the [CoTherix] story so badly needed," Fein enthused in a research note. "For this significantly sized carrot, we believe CoTherix paid relatively little."
The company also this spring brought aboard Abhay Joshi as executive vice president and chief technical officer. Joshi most recently served as vice president of global technical operations in specialty pharmaceuticals at Allergan Inc., where he managed global biologics manufacturing operations for the blockbuster wrinkle treatment Botox (botulinum toxin), also handling Latin America and Asia Pacific pharmaceutical operations.
Earlier this month, United Therapeutics Corp. signed a licensing deal with specialty pharma firm Supernus Pharmaceuticals Inc. for the ongoing development of UT-15C, the former's sustained-released prostacyclin analogue. UT-15C is an oral formulation of treprostinil, which is the active ingredient in UTC's FDA-approved Remodulin for subcutaneous and intravenous treatment of PAH. Phase II/III trials are under way with an inhaled version, too. Analyst Jennifer Chao with Deutsche Bank predicted an 85 percent probability of a favorable outcome in the study, called TRIUMPH.
Meanwhile, the leader of the PAH pack remains Tracleer (bosentan), Actelion Ltd.'s endothelin agonist, cleared in Europe four years ago and approved in the U.S. in November 2001. Another 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 approved for PAH a year ago. It could turn out that combining a PDE5 inhibitor such as sildenafil with a prostacyclin will work even better against PAH than the mighty Tracleer when used with a prostacyclin.
In any case, Revatio has been picking up patients who've failed Tracleer. Ditto Ventavis. But the big money nearer term might be in persuading physicians to give up GlaxoSmithKline plc's Flolan (epoprostenol) in favor of another compound, as UTC is trying with its intravenous Remodulin.
Not to be overlooked is Myogen Inc.'s ambrisentan, a non-sulfonamide, propanoic acid-class, type-A selective endothelin receptor antagonist in Phase III trials. Top-line data in December showed the drug improved patients' exercise capacity, as well as time to clinical worsening.
Encysive Pharmaceuticals Inc. recently said regulators in Europe recommended approval there of Thelin (sitaxentan), the firm's oral endothelin blocker. In March, the FDA told Encysive that the drug is approvable in the U.S., and talks are ongoing with the agency.
It's a complicated field, but Fein hailed the CoTherix/Asahi deal as an important one despite needing "further insight into the timing of the developmental pathway and data on use of rho kinase inhibitors in indications such as stable angina" - and despite the chances for UTC's inhaled Remodulin. CoTherix's progress "marks an attractive entry point for long-term oriented investors," he wrote.