It's beginning to look a lot like Christmas for Cardiome Pharma Corp., which released topline Phase III results on Monday showing its lead atrial fibrillation drug, RSD1235, met its primary endpoint and showed safety advantages over existing therapies.
"Clearly, there is a very certain pleasant irony in the proximity of this data release to Christmas," said Bob Rieder, the company's president and CEO, in a conference call.
Wall Street investors seemed to agree. Cardiome's stock (NASDAQ:CRME) shot up 22.8 percent on Monday, or $1.38, to close at $7.43.
Data showed that the intravenous form of RSD1235 converted 52 percent of patients with recent onset atrial fibrillation (AF) to normal heart rhythm, while placebo converted only 4 percent. The primary endpoint was conversion of recent onset AF to normal heart rhythm for at least one minute post-dosing within 90 minutes of the start of dosing. The study also showed the product was safe and well tolerated.
"The drug had a very high efficacy rate, better than we expected," Cardiome's chief financial officer, Doug Janzen, told BioWorld Today. "And the safety profile continues to be unblemished. We're happy from both of those perspectives."
The Phase III trial, known as ACT 1 (Atrial Arrhythmia Conversion Trial 1), included 237 patients with recent onset AF, meaning they were treated more than three hours but less than seven days after experiencing the condition. It also included 119 patients with longer-term AF, in which they had the condition more than seven days but less than 45 days. Another 60 patients that participated had atrial flutter, bringing the total number of patients enrolled in the trial to 416.
In terms of safety, serious adverse events occurred in 18 percent of placebo patients and 13 percent of drug group patients within the 30 days following drug administration. Potentially drug-related serious adverse events occurred in 1.4 percent of patients receiving RSD1235 and no placebo patients.
Perhaps the most surprising safety data showed that there were no cases of drug-related "Torsades de Pointes," an arrhythmia side effect of many anti-arrhythmia drugs.
"Most other drugs in this field will have a Torsades rate of somewhere around 3 percent to 4 percent of patients," Janzen said. "It stops the ventricles from pumping."
While the company's initial data show RSD1235 brought the majority of recent onset patients back to a normal heart rhythm, data still are being analyzed to determine how long they kept that normal rhythm. However, Janzen said that most patients kept the normal rhythm until they were discharged at 24 hours.
"We're comparing ourselves primarily to electrical cardioversion," Janzen said. "Electricity doesn't stay in the system very long, either."
Atrial fibrillation is an erratic heartbeat, or arrhythmia, of the upper storage chambers of the heart that is caused by irregular electrical impulses. It can lead to stroke, congestive heart failure and sudden cardiac arrest.
Marketed drugs lack in efficacy and have serious safety risks, including drug-induced pro-arrhythmia.
Physicians often have shied away from using anti-arrhythmics because of the potential side effects, but Cardiome management said in the conference call that they expect that to change if RSD1235 reaches the market. RSD1235 selectively blocks ion channels in the heart that are known to be active during episodes of AF. Phase II data of 56 new-onset patients demonstrated that RSD1235 terminated AF in 61 percent of patients, compared to 5 percent with placebo, within 30 minutes of the end of infusion.
ACT 1 is the first of three Phase III trials evaluating RSD1235 in atrial arrhythmia patients. ACT 2 is studying the drug in up to 220 patients who have developed transient AF following cardiac surgery. ACT 3 began enrolling 350 patients in July testing RSD1235 in recent onset atrial arrhythmia. (See BioWorld Today, July 8, 2004.)
Cardiome expects to complete the ACT studies by the third quarter of 2005 and file a new drug application late in the year or early in 2006.
"We think the North American market is somewhere between $300 million and $400 million," Janzen said. "The number of patients is roughly 1 million."
In October 2003, Cardiome partnered the intravenous form of RSD1235 in North America with Fujisawa Healthcare Inc., of Deerfield, Ill. The Phase III ACT 1 data will trigger a $6 million milestone payment from Fujisawa to Cardiome. (See BioWorld Today, Oct. 17, 2003.)
The company is in discussions with partners for the IV form in markets outside of North America. It also owns 100 percent of the rights to the oral form of the drug, which is in Phase I trials.
"Our oral program is designed to keep people in normal rhythm longer," Janzen said.
The ACT 1 trial began in August 2003 and was carried out in 45 centers in the U.S., Canada and Scandinavia. While the early onset subset of AF patients was used in determining the primary endpoint, the overall study population demonstrated a significant benefit, as well. Of patients that experienced AF between the time frame of three hours and 45 days, 38 percent of those dosed with RSD1235 experienced termination of AF, compared with 3 percent of those dosed with placebo. In the longer-term AF population, 8 percent of drug patients and 0 percent of placebo patients had their AF terminated. Data for the atrial flutter patients will be released in January. Cardiome expects to give full study details at the Heart Rhythm Society meeting in New Orleans in May.
Aside from RSD1235 in its intravenous and oral formulations, Cardiome is developing a third clinical product called oxypurinol, a xanthine oxidase inhibitor. Oxypurinol is in a Phase II trial in patients with moderate to severe symptomatic congestive heart failure.
The product also received an FDA approvable letter in June to treat gout. Final approval could come upon Cardiome's submission of additional clinical and manufacturing data. (See BioWorld Today, June 25, 2004.)