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Verona Pharma's lead drug compound, RPL554, is a novel long acting inhibitor of both phosphodiesterase 3 and phosphodiesterase 4 enzymes, two enzymes known to be of importance in the development and progression of immunological respiratory diseases, particularly rhinitis (hay fever) and asthma. As a PDE 3 inhibitor, the drug is expected to result in bronchodilator actions, whilst the PDE 4 component is expected to be anti-inflammatory. This mechanism of action is also expected to be effective in the treatment of chronic obstructive pulmonary disease (COPD).
RPL554 was selected from a class of compounds co-invented by Sir David Jack, the former Director of Research at Glaxo who led the team that discovered many of the commercially successful drugs in the respiratory market.
The competitive advantages of RPL554 include the following:
- combining bronchodilator (PDE 3) and anti-inflammatory actions (PDE 4) in a single drug, something that is currently only achieved with a combination LABA and glucocorticosteroid inhaler,
- unique in not using steroids or beta agonists, which have known side effects,
- planned to be administered by nasal inhalation, thereby reducing the unwanted gastrointestinal side effects of many orally administered drugs, and
Following completion in May 2008 of toxicological studies of RPL554, the Company commenced in February 2009 a Phase I/IIa clinical trial of the drug at the Centre for Human Drug Research (CHDR) at Leiden in the Netherlands. In September 2009, the Company announced that it had successfully completed the trial, demonstrating that RPL554 has a good safety profile and has beneficial effects in terms of bronchodilation and bronchoprotection in asthmatics and a reduction in the numbers of inflammatory cells in the nasal passages of allergic rhinitis patients. In November 2010, the Company successfully completed a further trial that examined the safety and bronchodilator effectiveness of the drug administered at higher doses. In August 2011, the Company demonstrated that bronchodilation is maintained over a period of 6 days with daily dosing of RPL554 in asthmatics. In November 2011, the Company successfully demonstrated safety and bronchodilation of RPL554 in patients with mild to moderate forms of COPD. The Company is currently planning a trial to further assess the drug's anti-inflammatory actions.
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