September 2, 2019 | Disease
Nearly one half of American adults suffer from hypertension, or high blood pressure. Globally, there are over 1 billion people with the disease – a figure that has doubled over the last 40 years. The World Health Organization estimates that hypertension causes 7.5 million deaths each year.
The issue is not a lack of medication. There are dozens of treatments for hypertension, which work variously to reduce vascular tension and slow down the heart; many are generic. The first problem is that high blood pressure may build up slowly and with few symptoms, silently increasing people’s risk of heart failure, stroke and kidney disease without their awareness. The second problem is that even when hypertension is diagnosed, managing it can be a challenge. Patients have to remember to take multiple pills on a daily or weekly basis. And since you can’t reliably ‘feel’ blood pressure, monitoring is required to ensure it is within a safe range.
Sending all hypertensive patients for regular doctor’s checks is not feasible or sustainable, either for the individuals or the health system. Technology may be able to help: patients can now use Bluetooth-enabled blood pressure devices at home; apps can help remind them to take their medication; treatment algorithms can help direct clinicians toward the most effective and convenient drug regimens for a given individual. Drug categories associated with certain side-effects can be avoided: angiotensin-converting enzyme (ACE) inhibitors, for example, cause a cough that can lead to discontinuation. Angiotensin receptor blockers work similarly well, without the side-effect.
These are some of the features of a new home-based, care delivery program developed at Brigham and Women’s Hospital in Boston, MA. A pilot study among 130 participants, published in Clinical Cardiology in January 2019, helped over 80% of them bring their blood pressure under control in an average of seven weeks. The participants received devices that automatically transmitted readings to their medical records. They were able to talk regularly to specialists trained to use a treatment algorithm designed, in accordance with NICE and ACC/AHA guidelines, to optimally adjust medication dose and mix according to patients’ outcomes and needs. For example, combination drugs may be prescribed to reduce pill burden and encourage maintenance treatment among those who have achieved control.
Most cases of hypertension can be adequately controlled by current medication, if taken appropriately. A minority of patients may have resistant hypertension, however – when blood pressure remains stubbornly high despite treatment with at least three standard drug classes. Several drug development programs focus on resistant hypertension, aiming to widen the choice of fourth medications available to patients with this condition.
One of them is Idorsia’s Phase III candidate, aprocitentan, in development with Janssen – part of the same Johnson & Johnson that bought Idorsia’s parent company, Actelion, in 2018. The drug works by blocking the action of endothelin, which causes vessels to constrict. Aprocitentan is in the same class as Actelion’s Tracleer (bosentan), which helped build Actelion into Europe’s leading biotech, and follow-on Opsumit (macitentan). Tracleer and Opsumit are used for a rare vascular disease called pulmonary arterial hypertension, characterized by abnormally high pressure in the blood vessels of the lung.
Novartis’ neprilysin inhibitor, LHW090, is in Phase II development for resistant hypertension and chronic renal insufficiency; it works to widen blood vessels and encourages salt excretion in the urine. France’s Quantum Genomics thinks that its brain aminopeptidase A inhibitor candidate, firibastat, may offer a solution by combining multiple mechanisms in one – diuretic (eliminating water and salt to reduce blood volume), vasodilation (reducing vessel wall pressure) and lowering heart rate via the baroreflex. Firibastat has completed a Phase IIb trial.
Resistant hypertension is a challenging area for smaller companies, given the need to perform combination studies with other widely-used anti-hypertensives. The size of the studies required and the pricing achievable for such treatments may also provide a less compelling commercial proposition than rare diseases or other niche, underserved segments.
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