Originally published March 26.
By Turna Ray
ARCA has received a patent from the US Patent and Trademark Office on genetic methods for identifying heart failure patients most likely to benefit from the investigational beta-blocker bucindolol.
Patent number 7,678,824, entitled "Methods for Treatment with Bucindolol Based on Genetic Targeting," provides market exclusivity to ARCA for its approach to treating patients with heart failure.
Nearly three years ago, the Laboratory Corporation of America said it was working with ARCA to develop a companion test for bucindolol [see PGx Reporter 02-21-2007].
According to a 10-K filed by ARCA on March 4, ARCA has licensed to LabCorp the rights to commercialize a receptor genotype diagnostic for the beta-1 adrenergic receptor and the alpha-2C adrenergic receptor genotype. In return, LabCorp has agreed to develop the test, obtain FDA approval, and commercially launch it in parallel with the commercial launch of bucindolol.
LabCorp filed a premarket approval application for the companion test in January 2009. "The review is currently under extension," ARCA said in its 10-K filing, adding that it "believes that approval of the LabCorp PMA is dependent in part upon FDA approval of the [bucindolol] new drug application, if any."
On March 25, ARCA filed a revised clinical study protocol assessment with the FDA to study safety and efficacy of bucindolol in approximately 3,200 patients with chronic heart failure who have certain mutations in the beta-1 adrenergic receptor that might make them more likely to respond to the drug.
Derek Cole, ARCA's VP of investor relations and corporate communications, told Pharmacogenomics Reporter this week that the company filed its original SPA with the FDA in December. The FDA requested additional information, which the company submitted in the revised SPA filing.
The agency now has up to 45 days to review the SPA and make a go/no-go decision. "The final trial protocol may be significantly different from the company's SPA submission," ARCA said in a statement.
Even with FDA clearance of its SPA, ARCA must garner sufficient funding before it can start clinical trials.
On March 12, ARCA received a notice from Nasdaq that the company's stockholders' equity as of December 31, 2009, did not meet the minimum requirement of $10 million for continued listing on the stock exchange. According to the company, this notification does not affect the listing of the company's common stock at this time, and ARCA has 45 days to present a plan for regaining compliance or risk getting delisted.
ARCA reported research and development expenses totaling $10 million for 2009 compared to $11 million for 2008. As of December 31, 2009, ARCA had total cash and cash equivalents of $7.8 million.
"In light of ARCA’s strategic direction and capital needs, ARCA implemented a plan of restructuring in the second quarter of 2009," the company said in its 10-K. "ARCA implemented the restructuring plan in connection with its strategy to seek strategic alternatives for further development of [bucindolol] and to lower operating expenses to preserve its capital resources."
Once the SPA receives the agency's thumbs up and ARCA is able to obtain necessary funds to conduct the clinical trial, the company expects it can begin studies for its NDA filing after 12 months.
The FDA previously designated bucindolol for fast-track development based on the agent's potential to reduce cardiovascular mortality and hospitalizations in a genotype-defined heart failure population. If approved by the FDA, the company will market bucindolol under the trade name Gencaro.
"We are obviously pleased with the USPTO's issuance of this patent, which we believe will extend our pharmacogenetic intellectual property protection around bucindolol and, if approved for marketing, provide Gencaro market exclusivity into 2025," said ARCA CEO Michael Bristow.
He added that the drug, in combination with the companion diagnostic, "has the potential to help alleviate some of the problems encountered with the current standard of practice."
According to ARCA's Cole, the test under development would indicate whether patients considering treatment with bucindolol will be best responders, have comparable response to other beta-blockers, or be "unfavorable" responders.
Approximately 50 percent of heart failure patients harboring certain variants in the beta1-AR fall in the best responder category. Patients with a genetic variant in the pre-junctional alpha-2c-adrenergic receptor, marked by deleted or missing amino acids 322-325, fall in the "unfavorable" response category and comprise around 10 percent of heart failure patients.
In a paper published in Heart Failure in January, researchers concluded that in the Beta-Blocker Evaluation of Survival Trial, or BEST, adrenergic polymorphism substudy, the "norepinephrine lowering and clinical therapeutic responses to bucindolol were strongly influenced by the alpha-2C adrenergic receptor genotype."
According to industry estimates, there are approximately 5.7 million people in the US who suffer from heart failure and 670,000 new heart failure patients are diagnosed annually. This amounts to more than $37 billion in direct and indirect healthcare costs in the US.
If approved by the FDA, bucindolol will compete with other beta-blockers on the market such as Toprol XL and Coreg. "It is anticipated that both of these generic equivalents will be priced at less than the price of Gencaro," ARCA states in its 10-K filing.