SHANGHAI – Eddingpharm Co. Ltd. will develop and commercialize Cardiome Pharma Corp.'s atrial fibrillation drug, Brinavess (vernakalant), paying $1 million up front for the Greater China rights with potential for the Vancouver, British Columbia-based Cardiome to receive $3 million more in regulatory milestone payments.

Eddingpharm, a Shanghai-based specialty pharma company with a 600-person commercial sales force handling a portfolio of partnered, revenue generating products in the areas of clinical nutrition, oncology, antibiotics and respiratory systems. Their lead products are Zinacef, an antibiotic sold under the Glaxosmithkline plc brand name, and Lipofundin, which delivers fatty acids to patients in need of intravenous nutrition.

They also take on higher risk, early stage candidates such as their deal a few months ago with Ablynx NV, of Ghent, Belgium, for ozoralizumab (ATN-103), an anti-TNFa nanobody for all indications including rheumatoid arthritis. (See BioWorld Asia, Sept. 10, 2014.)

The newest addition to the lineup, Brinavess helps to stabilize atrial fibrillation.

Administered through an intravenous (I.V.) formulation, Brinavess has a rapid conversion of recent onset atrial fibrillation to sinus rhythm in adults outside of a surgery setting for seven days or less, and for post-cardiac surgery patients for three days or less.

Xiaoming Zou, chief business officer at Eddingpharm, told BioWorld Asia that the move to develop and commercialize Brinavess as the company's first foray into CDV.

"Although a new area for us, we believe it is a very suitable product for Eddingpharm to enter the cardiovascular space," explained Zou, "it is a highly specialized product for hospital-based emergency use, it is an IV product, and will likely only require a small sales team to handle it."

Known as a channel blocker, Brinavess prevents abnormal electrical activity that can lead to atrial fibrillation by blocking channels through which charged particles of potassium and sodium move through the muscle cells in the atria.

Given the regulations for obtaining an imported drug license (IDL) in China requires local trials, the drug is still a few years from being on the market. But in this case, the first step, getting approval to conduct a clinical trial (CTA) has already been granted. This approval alone can cost companies more than a year of waiting.

A couple of additional factors may help the CFDA with their decision process.

Brinavess is already marketed in more than 30 countries, including the EU where it was approved in 2010, and according to company materials, over 10,000 atrial fibrillation patients have been treated.

But the CFDA is most interested in how new drugs affect Chinese patients and requires specific data in this regard.

In November, Cardiome published positive results from an Asia Pacific phase III study carried out in 35 centers in Korea, Taiwan, Hong Kong and India. The study achieved the primary endpoint and showed 53 percent of 111 patients with recent onset atrial fibrillation lasting three hours to seven days returned to normal heart rhythm within 90 minutes of receiving an IV dose of Brinavess. This compared favorably to 12 percent of placebo patients. This data should help support a Chinese filing.

Brinavess has had its share of setbacks as well, and to date has not been approved by the FDA. After an initial positive response from the U.S. authorities, Cardiome was asked for additional information and the phase III trial was put on hold in 2010.

According to the company, "Cardiome plans to work with the FDA to lift the hold and resume clinical development for the U.S. market."

In fact, it was around this time Brinavess was being developed by Merck & Co. Inc., of Whitehouse Station, N.J., the MNC had acquired global rights in 2009. But in 2012, Merck handed back the global rights to Cardiome.

The China CTA was obtained with Merck. Zou said they still have several years to start clinical trials. Even with the phase III in Asian patients, it is likely Eddingpharm will need to conduct a separate phase III in China with a phase I PK study to demonstrate pharmacokinetic differences in Chinese people and other populations.

"We, along with our partner Cardiome, are talking to Merck and will approach CFDA to see how we will position it. We are also updating our trial protocol to fit into a new registration trial under the current policy. We have some work to do together with Cardiome to update it to find the most efficient path forward," Zou said.

This deal is not Cardiome's first in China. Sciclone Pharmaceutical Inc., of Foster City, Calif., has been marketing Cardiome's Aggrastat (tirofiban HCL) for acute coronary syndrome for several years.

"China is a market with significant opportunity and we have found a very competent partner in Eddingpharm who can unlock the full value of Brinavess in this rapidly growing region," said Karim Lalji, Cardiome's chief commercial officer.