3 Major Trends for Cardiac Drug Discovery in 2020

Without a doubt, we will remember 2020 as the year of the COVID-19 pandemic. For the biopharma and healthcare sectors, the focus was firmly on the rapid development of diagnostics, therapies and vaccines that could be produced at scale. But under the radar, other life science fields have been powering on – among them, the cardiac field.

While the cardiovascular therapeutics market has expanded steadily over the past few decades as disease prevalence and awareness have grown, the field has lagged behind when it comes to investment and innovation. This is likely due to the high cost of clinical trials and the notable lack of success bringing new drugs to market. In 2019, for example, oncology startups attracted 10 times more venture capital than their cardiovascular counterparts ($5.6 billion vs. $543 million). While there are many reasons for this investment differential, a dominant one is the adoption of precision oncology. Science has amassed a deeper understanding of cancer biology through years of basic research, allowing biopharma companies to develop and deliver therapies to the patient populations that are most likely to respond. Such associations have lessened the risk of failure in efficacy trials. Analogous translational biology platforms have begun to emerge in the cardiac disease field. These technologies are designed to help cardiac drug discovery follow in the footsteps of precision oncology.

Despite the setbacks of 2020, there is much to be optimistic about with respect to progress in cardiac drug discovery. Below is a recap of some of the major developments that unfolded in 2020, and what they mean for the future of cardiac medicine.

1. Success and failure in phase III trial readouts

In 2020, we saw immense clinical and financial success in the cardiac space, juxtaposed with a instances of trial failure that remind us just how challenging this field is.

Success: BMS signals the high value of cardiac therapeutics with $13.1B acquisition of MyoKardia

One of the most significant developments in 2020 was Bristol Myers Squibb’s $13.1B purchase of Myokardia. Founded in 2012, MyoKardia was a pioneer in applying precision medicine to cardiovascular diseases. Rather than attempting to find a one-size-fits all approach to treating heart disease in the general population, MyoKardia examined the underlying causes of specific cardiac myopathies and identified subsets of patients who share specific disease characteristics. It’s a step towards the kind of personalization that is now second nature in oncology – and it has been successful. In May 2020, the company announced that its pivotal phase III clinical trial of the beta cardiac myosin modulator mavacamten met its primary and all secondary endpoints, paving the way to its high-value acquisition.

This successful clinical trial result and meaningful financial return is likely to encourage more early capital investments in the cardiac space, which will allow innovators to branch out and apply up-and-coming technologies more aggressively to solve pressing health issues.

Failure: Amgen cuts its losses with Cytokinetics after the partnership generates unremarkable clinical data

While MyoKardia thrived, not every company had a successful year. Cardiac drug development is inherently costly and complex, causing many potential therapeutic developments to fall short. In an analysis of clinical trial outcomes between 2006-2015, fewer than one-quarter of cardiovascular phase II trials were successful. By phase III, the probability of success was 55%, the second-lowest out of the 14 disease areas analyzed. 

In October 2020, Amgen and Cytokinetics announced their phase III pivotal trial of omecamtiv mecarbil in heart failure met the primary endpoint but failed to demonstrate a reduction in cardiovascular deaths. This mixed response highlights the complex nature of cardiac drug development and the gaps that still need to be filled in our underlying knowledge of cardiac diseases. With more work required to identify patient populations and indications for whom the drug would be most beneficial, Amgen returned ownership of the cardiac programs back to Cytokinetics, ending its 13-year biopharma partnership.

2. Investors embrace emerging cardiovascular companies

Cardiovascular drug development has been notoriously lengthy, costly and challenging. In other words, a tough sell for startups in search of financing. But the industry is entering a promising new era.  In addition to pharma’s increased attention, venture capital investment has also picked up. Emerging companies are gaining traction and recognition for their ability to tackle key issues in the field, such as a lack of treatment personalization. In 2020, those companies were rewarded with significant financing rounds.

●       Verve Therapeutics raised $63 million in a series A2 financing round to further its gene-editing therapies for heart disease.

●       Small startup Novo Bioscience raised $4 million to advance its preclinical regenerative medicine program, which aims to repair and restore damaged heart muscle tissue.

●       Late in the year, BridgeBio Pharma and Maze Therapeutics announced a new joint venture, Contour Therapeutics, which unites Maze’s genetically driven approach to drug discovery with BridgeBio’s expertise in cardiac drug discovery and clinical development. It’s yet another push towards using precision medicine to treat cardiovascular diseases, for greater efficacy and clinical odds.

●       TARA Biosystems raised an additional $10 million to expand its precision cardiac disease drug discovery and development platform.

3. COVID-19 adds to the global scope of cardiovascular disease

In 2020, COVID-19 changed the landscape of cardiovascular medicine, potentially impacting the field for decades to come. In the first week of December, COVID-19 officially eclipsed heart disease as the number one killer in the United States. It dominated both the news and hospitals, causing individuals to delay or skip routine preventive care and assessments.

More stealthily, the disease itself may be causing long-lasting cardiovascular effects. One paper, published in July in JAMA Cardiology, reported on a study of 100 people who had recently recovered from COVID-19. Only 33% had required hospitalization, yet 60% showed signs of myocarditis (inflammation in the heart muscle). Other studies have shown that COVID-19 can cause a litany of cardiovascular disorders, such as arrhythmias, acute coronary syndrome and venous thromboembolism.

The Institute for Health Metrics and Evaluation (IMHE) projected that by November 30, COVID-19 had infected 15% of Americans. Scientists around the world are still investigating just how this virus damages the heart, who is susceptible and what the lasting effects will be. Given the extraordinary number of cases in the United States and globally, the healthcare burden and personal impact is likely to be enormous.

One Final Note…

Understandably, research in 2020 has been focused on COVID-19 therapies and vaccines, where incredible progress has been made in a compressed timeframe, highlighting the aptitude and agility we have as an industry to get necessary therapies to patients. I am excited about what the future holds as medical research advances some of these latest discoveries into 2021. These include a move towards greater patient personalization and segmentation. Multiple cardiac studies in 2020 applied this approach, taking us one step closer to bringing cardiovascular therapies into the world of personalized medicine.

Misti Ushio, PhD, is the founding CEO of TARA Biosystems