First drug for rare heart and lung disease offers new treatment option for people in the UK
Adempas® (riociguat) is available in the UK as the first drug treatment for CTEPH, to treat adult patients with WHO Functional Class (FC) II to III with inoperable or persistent disease to improve exercise capacity.2 CTEPH, which affects close to 1,300 people in the UK, is a rare form of Pulmonary Hypertension (PH), a severe, progressive and life-threatening condition of the heart and lungs3. Patients develop high blood pressure in the pulmonary arteries, which causes breathlessness, fatigue and hinders their ability to work and carry out everyday activities.4-8
The standard and potentially curative treatment for CTEPH is pulmonary endarterectomy (PEA), a surgical procedure in which the blood vessels of the lungs are cleared of the clot and scar material caused by the disease.9 But many patients (20%-40%) with CTEPH are inoperable.1,10,11 These patients urgently need effective new treatments to manage their disease.12
"This new drug is the only proven medical therapy to improve symptoms in patients with inoperable CTEPH. As a surgeon, I should emphasise that pulmonary endarterectomy surgery remains the first choice therapy to cure this condition, and all patients in the UK who have susptected CTEPH should be referred to their regional designated pulmonary hypertension expert centre for assessment. There are a significant minority number of patients who are unable to undergo surgery that might benefit from riociguat and it is reassuring to have another treatment option to help them." David Jenkins, Consultant Cardiothoracic Surgeon, Director National Pulmonary Endarterectomy Service.
"Until today there were no other treatment options, aside from surgery, for those diagnosed with this disease. CTEPH can have a devastating impact on the lives of patients who, on a daily basis, struggle to breathe and experience dizziness and fainting, all which can be very frightening. As such riociguat is the start of a new era in the management of CTEPH." Iain Armstrong, Consultant Nurse, Royal Hallamshire Hospital
Riociguat is a soluble guanylate cyclase (sGC) stimulator, the first member of a new class of compounds discovered by Bayer HealthCare.13,14 With its new mode of action, riociguat has been developed as an oral treatment to target a key molecular mechanism underlying this serious disease.13,14
Prof. Johannes-Peter Stasch, Chief Scientist at Bayer and lead in the discovery of Riociguat and sGC stimulators, commented: "The availability of riociguat is a landmark in our mission to bring this urgently needed treatment to patients living with CTEPH or PAH. We are proud to have led the way in this disease area and to be the first company to have succeeded in bringing a proven CTEPH treatment from the laboratory bench to the patient bedside."
Results from a pivotal phase III trial, CHEST-1, showed that riociguat is the first ever drug to provide statistically significant clinical efficacy in patients with inoperable CTEPH or recurrent or persistent disease after surgery. Riociguat significantly improved patients' exercise capacity, measured using the six-minute walk test (6MWT), a marker of disease progression and mortality.15 In CHEST-1, patients receiving riociguat were able to walk an average of 46 additional metres (95%-CI [25-67 meters] p<0.0001) in the 6MWT from baseline after 16 weeks compared with placebo.15 There were also significant improvements in other markers of disease severity including patients' cardiopulmonary haemodynamics, WHO Functional Class and disease-related biomarkers.15
Riociguat is also indicated to treat patients with PAH, another type of PH in which the prognosis for patients remains poor despite the availability of several approved PAH therapies.16,17 Riociguat demonstrated statistically significant improvement in exercise capacity in treatment-naïve PAH patients as well as in patients pre-treated with an endothelin receptor antagonist or prostanoid monotherapy, in the PATENT-1 pivotal Phase III trial.18 PATENT-1 patients treated with riociguat were able to walk an average of 36 additional metres (95%-CI [20-52 meters] p<0.0001) from baseline compared with placebo in the 6MWT.18 Riociguat also met a range of other markers of disease severity, including cardiopulmonary haemodynamics, WHO functional class, disease-related biomarkers and time to clinical worsening.18
About Pulmonary Hypertension
Pulmonary hypertension (PH) is a severe, progressive, life-changing and life-threatening disorder of the heart and lungs in which the blood pressure in the pulmonary arteries is above normal, and which can lead to heart failure and death.4,5 Patients with PH develop a markedly decreased exercise capacity and a reduced quality of life.8 The most common symptoms of PH include shortness of breath, fatigue, dizziness and fainting, all of which are worsened by exertion.6,7 As the symptoms of PH are non-specific, diagnosis can be delayed by as much as two years.8,19,20 Early diagnosis and accurate identification of the PH type are essential as a delay in treatment initiation can have a negative impact on survival.8,21 Continuous treatment monitoring is then vital to ensure that patients are receiving optimal care for their particular type and stage of disease.8
There are five types of PH; each type can affect the patient in a different way and every patient may have a different aetiology and manifestation of PH.8,9,19
About Chronic Thromboembolic Pulmonary Hypertension (CTEPH)
CTEPH is a rare, progressive and life-threatening disease and a type of PH, in which it is believed that thromboembolic occlusion (organised blood clots) of pulmonary vessels gradually lead to an increased blood pressure in the pulmonary arteries, resulting in an overload of the right heart.8,9 CTEPH may evolve after prior episodes of acute pulmonary embolism, but the pathogenesis is not yet completely understood.9
About Pulmonary Arterial Hypertension (PAH)
PAH, one of the five types of pulmonary hypertension (PH) is a progressive and life-threatening disease in which the blood pressure in the pulmonary arteries is significantly increased due to vasoconstriction and which can lead to heart failure and death.4,8 PAH is characterised by morphological changes to the endothelium of the artery of the lungs causing remodelling of the tissue, vasoconstriction and thrombosis-in-situ. As a result of these changes, the blood vessels in the lungs are narrowed, making it difficult for the heart to pump blood through to the lungs.4,5 PAH is a rare disease and affects an estimated 15-52 people per million.4,5 It is more prevalent in women than men.22 In most cases, PAH has no known cause and, in some cases, it can be inherited.7
Riociguat is a soluble guanylate cyclase (sGC) stimulator, developed by Bayer as an oral treatment to target a key molecular mechanism underlying PH.13,14 Riociguat is being investigated as a new and specific approach to treat different types of PH.13,14 sGC is an enzyme found in the cardiopulmonary system and the receptor for nitric oxide (NO). When NO binds to sGC, the enzyme enhances synthesis of the signalling molecule cyclic guanosine monophosphate (cGMP). cGMP plays an important role in regulating vascular tone, proliferation, fibrosis, and inflammation.23
PH is associated with endothelial dysfunction, impaired synthesis of NO and insufficient stimulation of sGC.13 Riociguat has a novel mode of action - it sensitizes sGC to endogenous NO by stabilizing the NO-sGC binding. Riociguat also directly stimulates sGC via a different binding site, independently of NO.13,14,23 Riociguat, as a stimulator of sGC, may also address the issue of NO deficiency, which is linked to mortality in PAH and CTEPH, by restoring the NO-sGC-cGMP pathway, leading to increased generation of cGMP.13
With its novel mode of action, Riociguat has the potential to overcome a number of limitations of currently approved PAH therapies, including NO dependence,13 and is the first drug which has shown clinical benefits in CTEPH, where no other pharmacological treatment is approved.1,2
The CHEST-1 and PATENT-1 studies showed riociguat was well-tolerated with an acceptable safety proile.2,15,18 Riociguat has been formulated to enable personalised oral dosing to help meet the needs of each individual patient.