Posted by Michael Gralinski, Chief Executive Officer at CorDynamics on May 24th, 2012
By a narrow margin, an FDA Cardiovascular and Renal Drugs Advisory Panel advised against expanding marketing indications to prescribe Xarelto as an acute coronary syndrome therapy.
Fast Facts
• Xarelto (rivaroxaban) is a factor Xa inhibitor—a blood thinner. The drug already is approved for stroke in patients with nonvalvular atrial fibrillation. It’s also indicated for those undergoing joint replacement surgery to prevent deep vein thrombosis.
• Acute coronary syndrome (ACS) is a catch-all phrase referring to conditions involving coronary artery obstruction.
• The studies under review evaluated the safety and efficacy of rivaroxaban in more than 19,000 ACS patients in addition to aspirin with or without thienopyridine therapy.
• If the panel had advised approval it would have meant an endorsement of treating ACS patients with combination therapy (aspirin, thienopyridine and rivaroxaban).
Denied. Why?
The outcome was surprising based on the positive feedback released by FDA staffers earlier in the week.
Although the trial seemed to show the drug helped reduce the risk of dangerous blood clots in patients with serious heart problems, it also suggested an increase in bleeding that made 6 of the 11 panelists hesitate.
Advisors cited clinical study design and incomplete information as reasons for the denial.
The FDA is not required to follow the advice of the committee…but it almost always does.
What Does This Mean for Drug Developers?
Although some of the panelists weren’t convinced, they suggested a second trial might change their decision.
Once developers clear the hurdle of finding a compound with promise, the bar is set high for proving their efficacy and superiority over existing drugs to gain regulatory approval.
Most heart failure medicines have to go through a variety of different measures for efficacy. One of which is “quality of life” as measured by the American Heart Association ratings for heart failure. For example: Can bedridden patients begin to get out of bed and move around more?
The ultimate test for pending heart failure therapies are morbidity and mortality trials. Does the compound delay or prevent morbidity (the disease) as well as mortality. These comprehensive trials require patients numbering in the thousands. Studies of this scope, with high recruitment costs and long treatment periods, are an incredibly expensive investment.
Why try? According to the American Heart Association, the need is great and growing.
• An estimated 5.7 Americans, of all ages, suffer from heart disease.
• Heart failure is the fastest-growing clinical cardiac disease entity in the United States, affecting 2% of the population.
• In 2010, the estimated total cost of heart failure in the US was $39.2 billion, representing 1-2% of all health care expenditures.
Heart failure therapies may be hard to get, but for a number of our clients, these numbers make it worth the passionate pursuit.
Collaboration + Comprehensive Preclinical Studies
The compound RO5657, a CCR5 antagonist, had induced torsades de pointes (a life threatening cardiac arrhythmia) in normal, healthy animals. Employing a variety of preclinical cardiovascular models, the article investigated how and why a small-molecule compound exhibited cardiac side effects and torsades de pointes during preclinical toxicology studies.
The sponsor came to us to discuss the issues and contracted us to perform both anesthetized canine and non-human primate cardiovascular telemetry studies. The project became a textbook case of collaboration and integration.
Here’s the deal: when conducting screening studies of compounds on ion channels or isolated Langendorff hearts, you often don’t have the luxury to examine the other general toxicology study results concurrently. In this case, once all the studies were completed, we were able to confer and put them into perspective.
In fact, the ion channel and isolated heart interrogations ultimately predicted the anesthetized, telemetry and toxicology study results.
This article confirms the importance of collaborating, taking the information garnered from a variety of safety pharmacology and preclinical toxicology models, and compiling the results to produce an integrated cardiovascular risk assessment.
This type of approach is vital to making rationale project decisions—and ultimately getting a clear, complete picture.
The heart of our business is in the heart of the city of Chicago.
A contract research organization specializing in cardiovascular drug discovery, safety and efficacy in Chicago? Why Chicago?
We believe the city of Big Shoulders gives us big advantages.
Proximity to world-class universities, thought leaders and talent—The University of Chicago, University of Illinois at Chicago, Northwestern University, Loyola University and DePaul.
Access to O’Hare International Airport and daily flights to almost anywhere in the world.
Centrally located in the Midwest for access to clients on both Coasts and worldwide.
Not to mention, Chicago is a great place to welcome guests and colleagues.
If you’ll be in town for the American College of Cardiology Annual Conference, or any other time, let us know. We’d love to meet with you, give you a tour of our facilities and show you some of our favorite Chicago hot spots.
Posted by Michael Gralinski, Chief Executive Officer at CorDynamics on March 23rd, 2012
Society of Toxicology Feedback: Cautiously Optimistic
The takeaway from our productive trade show exhibit at the Society of Toxicology Annual Meeting in San Fransisco, was that the industry as a whole is cautiously optimistic—with an emphasis on the optimistic.
Vendors, clients, colleagues and investors stopped by the CorDynamics booth to check in and share the current state of business at their organizations.
The industry continues to try to balance the need for progress with efficient R&D expenditures.
In spite of constraints on hiring and large capital spending, projects are continuing to move forward with increasing momentum—especially early stage development and discovery endeavors.
Equity investors, a group usually more restrained in their use of financial superlatives, seemed to continue to emphasize caution, but were intrigued to the promise of 2012 and beyond.
Discovering a Return to Discovery
At CorDynamics, we are seeing an early and compelling return to discovery programs that may have been de-prioritized in the recent past. New inquiries in areas such as ischemia and reperfusion injury, along with atrial fibrillation have increased as of late.
Fueling these discovery streams will help to fill the industry pipeline with promising compounds for the upcoming calendar.
Posted by Theresa Gralinski, Marketing Director at CorDynamics on February 01st, 2012
Friday is “Go RED for Women Day!”
I’m Wearing Red on Friday.
I’ve always loved to wear red.
Maybe it stems from my time as an undergrad at the University of Wisconsin, where the school colors fly red and white and one of the favorite anthems is “Go Big Red.”
Or maybe, it’s because working for CorDynamics, I’m consumed with all things cardiovascular, have learned about heart disease and the startling statistics as they relate to women.
Do You Know These Heart Facts?
Heart disease—including heart attacks and strokes—is the number 1 killer of women.
Heart disease is the cause of death for 1 in 3 women.
Women are dying at the rate of 1 per minute—many of whom never knew heart disease kills.
Many women think they are too young, too healthy or even too busy to have a heart attack. That’s what my petite, energetic mother thought when she had a stroke at 54. She fully recovered, and is now making 68 look like the new 40, thanks to those around her who knew the warning signs of a stroke and acted quickly.
Do You Know the Warning Signs of a Stroke?
Sudden numbness or weakness of face, arm or leg, especially on one side of the body.
Sudden confusion, trouble speaking or understanding.
Sudden trouble seeing in one or both eyes.
Sudden trouble walking, dizziness, loss of balance or coordination.
Sudden severe headache with no known cause.
So on National Wear Red Day, Friday, February 3, I’ll being wearing red, to raise awareness for heart disease and in honor of my mom. I hope you join me.
Posted by Michael Gralinski, Chief Executive Officer at CorDynamics on January 30th, 2012
There are currently about 7,000 orphans out there waiting to be adopted, to be supported, to be cured. Many of us don’t even know their names: Kawasaki. Porphyria. Pulmonary Arterial Disease.
Orphan Status is a designation given by the FDA to identify rare diseases with unmet medical needs but with potentially promising compounds currently being researched. Orphan drugs receive expedited FDA reviews and fast tracks to clinical trials, providing hope for cures, treatments or comfort.
>>>>> Nearly 2,400 experimental compounds have orphan drug designations.
>>>>> So far, only 367 of these orphan drugs have been approved by the FDA.
Experts agree, coordinated collaboration and resources on all fronts will be the key to finding a potential drug therapy for these orphan drugs. Collaboration is also essential for the rare diseases still searching for enough answers to even begin the orphan drug development stage.
You may ask, what can I do to help? What can my organization do?
Adopt An Orphan
Pick an orphan disease with a compound in the works or a rare disease to adopt.
Show your support and learn more about the disease, follow related organizations on Facebook or in the news. One that we follow on Facebook is Two Hearts Rock and Global Genes Project.
Donate your time, participate in a sponsored event, or fundraiser.
“Wear That You Care” on World Rare Disease Day, February 29th. Wear “jeans” for “genes” and encourage your workplace, schools, and sport teams to do so too to raise awareness for the Global Genes Project.
Posted by Michael Gralinski, Chief Executive Officer at CorDynamics on December 15th, 2011
The CorDynamics team is closing out a successful year and setting the stage for 2012. Closing one calendar and turning to a new one, some of the first dates to fill in are our trade show exhibitions.
For the first time, we’ll take our booth to the Experimental Biology meeting in San Diego April 21-25. As we continue to grow the drug discovery side of our business, I look forward to attending this event and meeting with colleagues focused on this exciting and important side of drug discovery.
In addition to EB, we’ll also be exhibiting at SOT, SPS and ACT.
Society of Toxicology 51st Annual Meeting
San Francisco, March 11-15
2012 Safety Pharmacology Society Annual Meeting
Phoenix, October 1-4
American College of Toxicology 33rd Annual Meeting
Orlando, November 4-7
If you’re going to be at any of these meetings, please put connecting with us on your calendar.
Posted by Theresa Gralinski, Marketing Director at CorDynamics on December 02nd, 2011
Drug development researchers have been putting a lot of emphasis on collaborating in the effort to produce safe and effective drugs as quickly as possible. This is especially true in the area of rare disease research.
The CorDynamics team collaborates day in and day out—with each other, with colleagues, with our clients and their project teams. But collaborating is kind of like parenting, you think and hope you are doing it well but there isn’t a definitive gauge to tell you if you are making progress.
PAH—an orphan disease, with unmet medical treatment—is characterized by increased blood pressure in the arteries of lungs, causing dizziness, shortness of breath and can lead to heart failure. Current therapies for pulmonary artery hypertension (PAH) improve longevity and performance of daily activities in the lives of PAH patients, but do not notably affect the disease processes that lead to morbidity and mortality. Since serotonin has a definitive role in the development of PAH, the authors hypothesized that interfering with serotonin function may reduce the vascular remodeling and hemodynamic changes that occur in this preclinical model.
With the industry continuing to embrace a collaborative environment, I look forward to more research results that will ultimately provide more treatment options for patients in the future. As far as my kids and my parenting skills go, I guess I’ll have to assume no coal in their stockings means I’m doing something right and continue to believe.
Posted by Peter Senese, Chief Operating Officer at CorDynamics on November 18th, 2011
Pull-ups are hard and much more difficult than pushups, especially as I am pushing 50 years old. Although as I see the decreasing number of sequential push-ups possible for me, I embrace our ability to adapt to changing conditions and information in order to capably master that which used to come much more easily.
In addition to this last minute body-building, many other preparations were necessary for our October rock climbing trip at Devil’s Lake State Park in Baraboo Wisconsin with Boy Scouts of America Climbing Venture Crew 317. My friend, Steve Toth and I started Venture Crew 317 in 2003—at nearly the same time that CorDynamics, Inc. was founded. CorDynamics sponsored this climb, like many others.
The relationship between the cardiovascular symptoms such as that pounding-in-the-chest feeling, syncope and high heart rate with the adrenaline release of rock climbing had became evident to me several years earlier. I stood on top of my first rappel (lowering yourself down a rope) of a 40-foot cliff at the very same Devil’s Lake park on a dark, snowy afternoon. Steve was there goading (now in the BSA, we don’t goad, we “challenge by choice”) me over the edge. He was confident in the knots he inspected on my brand new climbing harness; I checked everything over nearly 20 times. I did make it down and my adventures on the edge began.
Fast forward to our October event with the 14 climbers of Troop 373 out of Wheaton, Illinois we had set an ambitious agenda:
• Friday night campout for the trained personnel.
• Early Saturday wake-up and climb for leaders to set up multiple anchor systems high on the cliffs.
• A set of climbs ranged in difficulty from easy to expert are roped up.
• The Troops arrive for safety and procedural orientation as well as knot-tying instruction at the trailhead.
As the Scouts completed their heart-racing ascents, they too experienced first-hand the connections between cardiovascular health, testing limits and climbing. What a natural fit for CorDynamics and this series of adventures we are proud to support.
