Innovations in PAH

19.06.2012 09:32

On the occasion of the 9th German P(A)H Forum in Berlin, conference president Prof. Dr. med. Ardeshir Ghofrani from the University Hospital of Giessen and Marburg gave an overview of the upcoming innovations in the treatment of pulmonary arterial hypertension (PAH).

Dual endothelin blockade with the active ingredient bosentan has been around for ten years and has revolutionized the treatment of PAH. Just a decade ago it was considered a success, according to Prof. Dr. med. Ralf Ewert from the University Hospital of Greifswald, if 50 percent of the patients on the waiting list for a lung or heart-lung transplant did not die. The EARLY study with Bosentan/Tracleer from Actelion - incidentally the only study in which only patients in NYHA class II were treated - would have shown that early start of therapy can delay disease progression. And the successor drug, which can be measured on primary endpoints for the first time, is already available: “Macitentan”, also from Actelion. In the RC trial of this drug, in which 742 patients with pulmonary arterial hypertension (PAH) were treated for up to three and a half years, the two doses used (3mg and 10mg) reduced the risk of morbidity or morbidity over the course of the treatment period Mortality event and with 3 mg by 30 percent (p=0.0108).

However, despite this progress in the field of PAH, survival rates are still too low and the disease remains incurable. And it probably won't be any time soon. Although conference president Prof. Dr. med. Ardeschir Ghofrani from the University Hospital of Gießen and Marburg presented further innovations in addition to “Macitentan”, but he also said very clearly that although there is currently no prospect of a cure for PAH, the constantly growing knowledge of the molecular and cellular processes in the affected vascular areas of the lungs is with us could bring us closer to this goal in the long term.
He sees, for example, an improvement in NO-sGC-cGMP-mediated signal transduction as promising, such as: B. by stimulating soluble guanylate cyclase. Tyrosine kinase inhibitors also offer hope for a new antiproliferative therapy for the disease (PAH), in which proliferation plays a central role in vascular obliteration. However, the effectiveness and toxicity of these active ingredients still need to be tested further.
The prostacyclin receptor agonist “Selexipag” would also be examined in the study “Prostacyclin (PGI2) Receptor agonist In Pulmonary HypertensiON”, GRIPHON for short, as well as the 5HT2a and 5HT2b antagonist “Terguride” from Ergonex Pharma, which is involved in the study “TERPAH” is also in phase II clinical development. And also the evaluations of the RC studies “Chronic-thromboembolic pulmonary hypertension sGC-Stimulator Trial” (CHEST) for “Riociguat” (“Xarelto” from Bayer Schering Pharma) and “IMatinib in Pulmonary Arterial Hypertension” (IMPRES) for imatinib ( “Gleevec” from Novartis) is coming soon.