KING OF PRUSSIA, Pa.—Almost two months to the day afterannouncing Phase IIa trial results for the intravenous drug TRV027, TrevenaInc., a clinical-stage pharmaceutical company with a focus on the discovery anddevelopment of G protein coupled receptor (GPCR) biased ligands, announced acollaborative licensing option agreement for TRV027 with New York-based ForestLaboratories Inc. through its subsidiary Forest Laboratories Holding Ltd.
Trevena expects to commence a 500-patient multicenter PhaseIIb clinical trial for the angiotensin II type 1 receptor (AT1R) biased ligandin acute decompensated heart failure (ADHF) by year's end. The results of thePhase IIa study, which ended in October 2012, came out officially on March 8.
Neither party has given out details about the deal, but theydid note that it includes a $30 million equity investment by Forest,essentially leading Trevena's $60-million Series C financing round. The termsalso call for the grant by Trevena to Forest of an option to exclusivelylicense TRV027 on a worldwide basis following completion of the planned PhaseIIb clinical trial, which will be funded by Trevena.
Reportedly, the companies are establishing a jointdevelopment committee to oversee the development of TRV027, with Trevenaretaining operational authority during the option period. Following theexercise of the option, Forest would make payments of as much as $430 million,depending upon the achievement of future development and commercial milestones,plus royalties, and would have responsibility for the development andcommercialization of the product.
According to David Solomon, Forest's senior vice presidentof corporate development and strategic planning, "TRV027 represents animportant opportunity for Forest to build on our presence in the cardiovascularmarket and the hospital segment. ADHF is the fourth-leading cause ofhospitalizations in the United States and there has been no material change inthe standard of care for patients with ADHF for decades. TRV027 has thepotential to be a significant new advance in the treatment of ADHF because itaddresses the underlying pathophysiology of the disease which has beendemonstrated in preclinical and early clinical work by Trevena."
Maxine Gowen, Trevena's president and CEO sees the Forestdeal, announced May 9, in part as a chance to further validate her company'sbiased ligand approach to GPCR drug discovery, adding that "Forest Labs bringsa wealth of drug development and commercialization experience to the TRV027program. This collaboration provides us with an opportunity to maximize thepotential of this promising compound."
TRV027 is a novel beta-arrestin biased ligand of AT1R thatis said to combine the proven benefits of angiotensin blockade with newbeta-arrestin-mediated biology to preserve cardiac and renal function.
In the Phase IIa results presented at the American Collegeof Cardiology meeting in March, Trevena showed that TRV027 was generally welltolerated and reportedly produced a beneficial set of hemodynamic effects.
The completed Phase IIa study was a randomized,double-blind, placebo-controlled, adaptive, ascending dose-titration study toevaluate the safety, tolerability, pharmacokinetics and invasive hemodynamicsof TRV027 in patients with stable NYHA Class 3 and 4 heart failure.Thirty-three catheterized patients were enrolled at centers in the UnitedStates and Europe. Twenty-four patients received TRV027 and nine patientsreceived placebo.
"TRV027 is the lead asset in our biased ligand portfolio,and we are delighted that these results support its progression to aproof-of-concept study in ADHF," Gowen said in March.
The American Heart Association (AHA) estimates that ADHFhospitalization costs the U.S. healthcare system alone more than $20 billioneach year in direct spending, not to mention that ADHF is reportedly theleading reason for hospitalization of individuals over 65 years old in theUnited States at more than 1.3 million hospital admissions per year.Furthermore, the AHA says, ADHF is the most costly diagnosis for Medicare.
Despite the significance of this problem, current therapiesare not producing meaningful improvements in patient outcomes, Trevena andForest Labs note, adding that ADHF incidence is increasing globally, and bothheart failure mortality and hospital re-admission following an ADHF eventremain extremely high.