BIO’s Industry Analysis team has published its 5th report in a series on the innovation landscape of highly prevalent, chronic diseases. This new report [available here] reviews the state of drug development for hypertension and heart failure. As with the prior reports, the investigation into these cardiovascular indications is meant to help industry stakeholders identify and understand the extent of any R&D contraction for these indications. Thus far, we have identified a broad contraction of R&D in depression, pain, addiction, type II diabetes, and obesity.
The cause for concern is magnified by the impact these chronic disease areas have on the overall healthcare system in the U.S. For cardiovascular disease alone, the American Heart Association estimates current direct costs at $277 billion annually in the U.S. and expects direct costs to grow to $655 billion by 2035.1 Although these current and projected costs for cardiovascular disease are staggering, venture capital investment for cardiovascular-focused therapeutic companies in the U.S. remains 13 times lower than oncology-focused companies.
Furthermore, the cardiovascular clinical pipeline has barely grown, with only a 3% increase in the number of programs since 2015.
Combined with recent exits out of cardiovascular disease by larger pharmaceutical companies and stagnating growth in the clinical pipeline, these low venture funding levels suggest there may be fewer innovative solutions in the future. We decided to focus our investigation on two highly prevalent indications: hypertension, a disease that effects some 96.1 million people in the U.S. alone, and heart failure, which has a prevalence of the 5.8 million people in the U.S.1
Key Takeaways for Systemic Hypertension Therapeutics
- Highly genericized market: Only one new drug class has been approved over the last 20 years. There are currently 68 FDA-approved new chemical entities (NCEs) for treating hypertension.
- Tiny Pipeline: Of the 18 clinical-stage drug programs for treating hypertension, only 6 programs are aimed at new molecular targets. Only one of these is in Phase III.
- Weak Investment into clinical studies: Phase I trial initiations have declined over the last decade, with 16 trials from 2009-2014 vs seven in the period 2012-2018. Phase II trial starts do not show a detectable trend, with only one to three trial initiations per year. Phase III trial starts have ranged from no trial starts to only one or two depending upon the year.
Key Takeaways for Heart Failure Therapeutics
- Highly genericized market, with most of the drugs co-indicated with hypertension: There are currently 31 FDA-approved new chemical entities (NCEs) for treating heart failure and 87% are also approved for systemic hypertension. Only two approved NCEs had unique molecular targets approvals in the last decade.
- Small but broad pipeline: Of the 28 clinical-stage drug programs for treating heart failure, 23 involve NCEs across 14 new molecular targets. There are three times as many novel programs in heart failure than hypertension.
- Increasing Phase II trial initiations: Phase II trial starts have increased from a low of two in 2009 to eight in 2018, suggesting an increased focus on innovative R&D. Phase III trial starts, however, have remained at two or less per year over the last decade. The relative number of trial starts is significantly below trial starts in sub-indications for oncology.
This is a relatively small novel drug pipeline given the unmet need, high prevalence, and high social and economic burden for these indications. Why is this the case? The main obstacles include the inability to stratify patient populations, lack of understanding of the pathophysiology behind certain subtypes of the disease, challenging and costly regulatory requirements, and a difficult reimbursement environment.
The Biotechnology Innovation Organization (BIO) and member companies view drug innovation as the key to helping patients with cardiovascular disease. Advancements in science, more choices for patients, and a policy environment that stimulates greater investment in R&D are necessary to achieve this goal.
- American Heart Association. Cardiovascular disease: A Costly Burden for America, Projections Through 2035 (total costs above do not include stroke and are specific for hypertension and heart failure)