A Boehringer SVP and BioSig's CEO dish on the 'heart' of innovation
This year, oncology, neurology, and specialty therapies in general are hot topics. Attention-grabbing headlines tout new immuno-oncology breakthroughs and promising Alzheimer’s candidates, reflecting a newfound level of innovation in addressing unmet medical needs in specialty categories.
But what about primary care? What about the unmet medical needs in basic areas such as cardiovascular disease?
A surprising uptick in death from atrial fibrillation
The need for innovation in this space is real: Cardiovascular disease (CVD) continues to be the leading cause of death for both men and women in the U.S. Every year, about 610,000 people die from CVD, while another 130,000 people die from strokes—including many caused by underlying atrial fibrillation (AF), which affects 2.7 million people in the U.S., making it the most common type of arrhythmia.
Despite the fact that many patients who have been diagnosed with AF think it’s harmless, in fact, AF increases the risk of stroke five-fold. Even worse, when a person with AF has a stroke, it is generally more severe and complicated than when there is no underlying arrhythmia.
Despite the availability of various anticoagulant treatment options, as well as surgical intervention, AF continues to be an area of unmet medical need. In fact, AF-related death rates have been increasing steadily for more than 20 years.
Although atrial fibrillation and cardiovascular disease have not been the source of lots of headline news this year, two companies have been working hard to innovate in this space. Boehringer Ingelheim (BI) just received FDA approval for Praxbind (idarucizumab), a reversal agent for its novel oral anticoagulant (NOAC) Pradaxa (dabigatran). And on the medical device side, BioSig Technologies is developing the PURE EP System to help improve decision-making and precision during cardiac ablation procedures in patients with AF.
The ups and downs of Pradaxa
For years, warfarin anticoagulation therapy was the mainstay treatment used to prevent stroke in patients with AF. However, it is notoriously difficult to use, with a narrow therapeutic index. The introduction of BI’s Pradaxa, a direct thrombin inhibitor, in 2010 was a major game changer.
"Pradaxa was the first NOAC approved in more than 50 years for reducing the risk of stroke in non-valvular AF (NVAF) patients," said Dr. Sabine Luik, Senior Vice President of Medicine & Regulatory Affairs at BI in an interview with BioPharma Dive. "One of the largest clinical trials for patients with NVAF, the pivotal RE-LY trial, established the benefits and safety of Pradaxa without the need for routine coagulation monitoring."
Within the next couple of years, Janssen introduced its NOAC, Xarelto (rivoroxaban), and Bristol Myers-Squibb (BMS) introduced Eliquis (apixaban), both of which were approved for the prevention of NVAF-related stroke indication. It was a brand new era of innovation in anticoagulation with one major downside—unlike warfarin, which could be reversed with vitamin K, there was no reliable way to reverse the effects of any of the NOACs.
Last year, amid reports of almost 300 Pradaxa-related deaths since the drug was approved, BI settled 4,000 lawsuits related to bleeding caused by the drug. Xarelto and Eliquis were also sources of concern for physicians, who wanted to know that they would be able to reverse bleeding if necessary after treating their patients with one of the "new" anticoagulants.
Just as BI trailblazed its way into the NOAC market, it also became a pioneer in developing a reversal agent for Pradaxa. "Dabigatran is now the only NOAC with an FDA-approved specific reversal agent—Praxbind," Dr. Luik explained.
"On October 16, the FDA approved Praxbind under an Accelerated Approval Pathway based on a reduction in unbound dabigatran and normalization of coagulation parameters in healthy volunteers. I should be note that continued approval for this indication may be contingent upon the results of an ongoing cohort case series study. The FDA also granted Praxbind Breakthrough Therapy Designation, and the application received Priority Review."
Innovation in surgical devices for addressing AF
Anticoagulation treatment is not the only strategy for addressing AF. Each year in the U.S., roughly 50,000 catheter ablations are performed in patients with AF, with the goal of cauterizing the abnormal electrical tissue inside the heart, thereby interrupting faulty electrical pulses. BioSig’s PURE EP system is designed to assist electro-physiologists in making real-time clinical decisions in response to cardiac signal recordings and other data as they hone in on their ablation targets.
Given the prevalence of AF, only a very small percentage of patients undergo cardiac ablation surgery, though it has the potential to be curative. "Less than 1% of people hospitalized with AF undergo catheter ablation, mainly because of concerns about high recurrence rates—almost half of patients who undergo the procedure need one or more additional procedures," said Greg Cash, CEO of BioSig, in an interview.
"This is because the current approach to AF treatment is anatomically based, rather than focusing specifically on the signals in the area of the heart that cause arrhythmia. Another reason for the low surgery rate is that many patients are cardioverted or treated with drugs rather than undergoing surgery. One of our long-term goals is to reduce the rate of AF recurrence after surgery."
Indeed, the innovation that’s driving advances in AF is occurring on parallel tracks, especially given the use of peri-surgical anticoagulants. As Cash explained, "When a patient develops AF, it greatly increases the potential for blood clots to form in the atrium, because of stagnant blood flow. If these clots embolize and migrate to the brain, they can cause strokes. Anticoagulants play an important role in preventing clot formations in Afib patients."
Clearly, the goal of medical and surgical advances in treating AF is to ultimately reduce the risk of stroke. Dr. Luik said that pivotal studies have shown that the approved NOACs reduce the risk of stroke by as much or more than warfarin (Note: Warfarin is associated with a 68% reduction in the risk of stroke in patients with AF). However, she also said, "How NOACs perform in clinical practice is currently being investigated."
As for BioSig’s data, the company is currently involved in a preclinical trial at Mayo and awaiting data, which should be ready for presentation at the Heart Rhythm Society in May 2016. It all points to the reality that innovation is not a one-time, big-breakthrough deal, but an ongoing assessment of what needs to be done to refine a new or existing therapeutic approach—and ultimately advance the standard of care.