Drugs with better pharmacodymics and improved treatment algorithm with antiproliferative and anti-inflammatory treatments are needed!

Pulmonary arterial hypertension (PAH) is rare lung disorder affecting pulmonary arteries. It is a fatal disease associated with the vasoconstriction and vascular remodeling that is characterized by progressive increase of pulmonary pressure and resistance leading to right heart failure. In most of the cases this disease is diagnosed in the late stage classified by WHO as Class III and IV. PAH is categorized as group one under pulmonary hypertension. History reports the emergence of this disease back in 1891 with the concept of hemodynamics. In 1973, World Health Organization (WHO) categorized the pressure rise in pulmonary arteries as primary and secondary pulmonary hypertension. Although it is a rare disease but it has estimated prevalence of 15-50 cases per million. Epoprostenol, a prostacyclin analog was the first drug to provide treatment for pulmonary arterial hypertension which was followed by improved therapies in oral forms acting as phosphodiesterase V inhibitors and endothelin receptor antagonists (ERAs). These therapies are designed to stimulate relaxation of pulmonary arteries but are not directly targeting vascular remodeling.

Research over last five years

Recently within past 5 years, there have been major advances in the treatment option for PAH with better understanding of pathophysiology. Newer paradigms have paved way for the future development of novel therapeutics targets. Endothelial dysfunction has become a major area of interest as therapeutic target for treatment of PAH. Other targets explored recently include Tyrosine Kinase (TK) inhibitors which involve growth factors such as bFGF, PDGF and EGF; Rho-kinases in signaling pathways, Dehydroepiandrosterone, miRNA, Gene therapy and Stem cell therapy. Combination therapies of approved drugs are also used in the clinical trials but it remains unknown whether it will prove to be more effective than other drugs. More than 20 drugs have reached in the clinical trials for the treatment of PAH indication.

Pharmaceutical Companies Researching in PAH

Novarts AG, GlaxoSmithKline PLC, Pfizer Inc and Eli Lilly & Co. are few giant bio-pharmaceutical companies whose products are in phase III and acts on novel therapeutic targets. Gilead Biosciences is coming up with the combination therapy in phase III. These all companies are expected to provide huge competition in the market to some of the already marketed drugs such as Tracleer (bosentan) which is set to go off-patent in US and Europe in 2015 and 2017. Other companies to look up to in future include Arena Pharmaceuticals, Inc., Dong-A PharmTech Co., Ltd. and Reata Pharmaceuticals. Celladon Corporation, miRagen Therapeutics, Inc., Silence Therapeutics and Northern Therapeutics, Inc. are other companies which are establishing themselves for the treatment of PAH by targeting gene, stem cell and micro RNA.

DelveInsight Expert Comments

The current treatments have shown symptomatic improvements but they do not provide the evidence of long term survival. The future clinical trials for PAH looks complex and challenging as it is an orphan disease deep insight knowledge of molecular biology. Drugs with better pharmacodymics and improved treatment algorithm with antiproliferative and anti-inflammatory treatments are needed that will target the pulmonary disease more specifically.

Written by Tarun Jain, Associate Analyst at DelveInsight

Upcoming Report:Pulmonary Arterial Hypertension – Competitive Landscape, Market & Pipeline Analysis, Forecasted Market Size 2015-2020

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