Gilead and Navitas Announce Agreement for Cicletanine for the Treatment of Pulmonary Arterial Hypertension
Cicletanine is an oral, once-daily agent that is approved in certain European countries for the treatment of hypertension. The compound is thought to act via enhanced coupling of endothelial nitric oxide synthase (eNOS). Cicletanine has been evaluated in three small pulmonary hypertension studies in Europe. In the United States, cicletanine is currently being evaluated for the treatment of pulmonary arterial hypertension (PAH) by Aaron Waxman, MD, PhD, Assistant Professor, Harvard Medical School, Director of the Pulmonary Vascular Disease Program, Pulmonary and Critical Care Unit, Massachusetts General Hospital, under an investigator-held compassionate use investigational new drug application (IND). Gilead plans to evaluate cicletanine for the treatment of PAH in a Phase II study which is expected to commence prior to the end of 2008.
"There remains an unmet medical need for people living with PAH," said Dr. Waxman. "I'm hopeful that further study of cicletanine will contribute to our growing understanding of this disease and ultimately benefit patients."
Under the terms of the agreement, Gilead will pay Navitas an upfront payment and contingent payments on future net sales. Navitas also could earn additional payments based upon the achievement of certain development and regulatory milestones. Gilead has acquired the exclusive rights to regulatory data and filings for development of cicletanine as a monotherapy for PAH and for other indications in the United States.
"Our agreement with Navitas is reflective of Gilead's commitment to building a pipeline of therapies for people living with PAH, including treatments with potentially novel mechanisms of action," said John F. Milligan, PhD, President and Chief Operating Officer, Gilead Sciences. "Based on the data available in patients with PAH and the strong safety profile, as established in hypertension studies, we believe this product has important potential to address the unmet medical need that exists in the field of PAH, and we will work to advance our development program forward as quickly as possible."
"We are pleased that Gilead will be driving development and commercialization of cicletanine for PAH," said Jim Page, President of Navitas Assets, LLC.
"Gilead's depth of scientific expertise and strength of market presence make them an ideal candidate for helping cicletanine realize its therapeutic potential," added Glenn Cornett, MD, PhD, CEO of Navitas Pharma, an affiliate of Navitas Assets.
Endothelial dysfunction, known to play a role in hypertension and PAH, is associated with a deficiency in vascular nitric oxide which is caused by decoupling of eNOS. This eNOS decoupling leads to reduced nitric oxide and increased superoxide production. In vivo studies suggest that cicletanine's eNOS coupling mechanism may directly target endothelial dysfunction by stimulating vascular synthesis of nitric oxide and inhibiting overproduction of superoxide. The efficacy of cicletanine in hypertension has been demonstrated in European clinical trials and through use in more than 10,000 patients. The safety profile of the drug is supported by a European dossier that describes approximately two million patient-years of post-launch exposure.
Cicletanine is an off-patent compound. Navitas has applied for orphan drug status for cicletanine for treatment of PAH. If orphan status is granted, Gilead would retain cicletanine U.S. market exclusivity for seven years from the time of U.S. Food and Drug Administration approval as a treatment for PAH.
About Pulmonary Arterial Hypertension (WHO Group 1)
PAH is a debilitating disease characterized by constriction of the blood vessels in the lungs leading to high pulmonary arterial pressures. These high pressures make it difficult for the heart to pump blood through the lungs to be oxygenated. Patients with PAH suffer from shortness of breath as the heart struggles to pump against these high pressures, causing such patients to ultimately die of heart failure. PAH can occur with no known underlying cause, or it can occur secondary to diseases such as connective tissue disease, congenital heart defects, cirrhosis of the liver and HIV infection. PAH afflicts approximately 200,000 patients worldwide.
Navitas Assets, LLC, is a privately-held company focused on the development of novel treatments for cardiovascular and metabolic diseases. Navitas Assets is headquartered in Laramie, Wyoming, with an additional office in Palo Alto, California.
About Gilead Sciences
Gilead Sciences is a biopharmaceutical company that discovers, develops and commercializes innovative therapeutics in areas of unmet medical need. The company's mission is to advance the care of patients suffering from life-threatening diseases worldwide. Headquartered in Foster City, California, Gilead has operations in North America, Europe and Australia.
Gilead Forward-Looking Statement
This press release includes forward-looking statements, within the meaning of the Private Securities Litigation Reform Act of 1995, that are subject to risks, uncertainties and other factors, including risks related to Gilead's ability to initiate a Phase II study of cicletanine as currently planned or at all. Gilead faces risks related to its ability to enroll patients in such a study, the possibility of unfavorable results of the study, the need to modify or delay our study or to perform additional trials and the risk of failing to obtain approvals from the regulatory authorities. As a result, cicletanine may never be successfully commercialized. Further, Gilead may make a strategic decision to discontinue development of cicletanine if, for example, we believe commercialization will be difficult relative to other opportunities in our pipeline. In addition, orphan drug status for cicletanine for the treatment of PAH may not be granted. These risks, uncertainties and other factors could cause actual results to differ materially from those referred to in the forward-looking statements. The reader is cautioned not to rely on these forward-looking statements. These and other risks are described in detail in Gilead's Annual Report on Form 10-K for the year ended December 31, 2007 and Quarterly Report on Form 10-Q for the first quarter of 2008, as filed with the U.S. Securities and Exchange Commission. All forward-looking statements are based on information currently available to Gilead, and Gilead assumes no obligation to update any such forward-looking statements.
For more information on Gilead Sciences, please visit the company's website at www.gilead.com or call Gilead Public Affairs at 1-800-GILEAD-5 or 1-650-574-3000.
Gilead Sciences, Inc.
Susan Hubbard, 650-522-5715 (Investors)
Nathan Kaiser, 650-522-1853 (Media)
Navitas Assets, LLC
Glenn Cornett, MD, PhD, 650-400-5100
James Page, MD, JD, MPH, 307-399-7276
Posted: May 2008