Chiesi Reports Successful Completion First-in-Man Phase 1 Study With Novel Inhaled PDE4 Inhibitor
PARMA, Italy, October 16, 2012 /PRNewswire/ –
Chiesi Group announces that it has successfully completed a Phase I trial of its
inhaled PDE4 (phosphodiesterase 4) inhibitor, denoted CHF 6001, a new chemical entity
developed for the treatment of inflammatory respiratory disorders, such as chronic
obstructive pulmonary disease (COPD) and asthma.
The phase 1 study was conducted to evaluate safety, tolerability and pharmacokinetics
after administration of single doses (up to 2000 microg) and repeated doses (up to 2000
microg for 7 days) to healthy volunteers. CHF6001 was well tolerated up to the highest
doses administered, both in single and multiple dose parts of the study, particularly with
respect to gastrointestinal side effects: an area which has posed significant development
hurdles for other PDE4 inhibitors in the past. No relevant safety findings, including
cardiac side effects were observed. The long-lasting exposure in the systemic circulation
supports once-a-day dosing. Based on these positive results, two phase 2a proof of concept
studies are ongoing in patients with asthma and COPD.
About CHF 6001
CHF 6001 is a novel selective PDE4 inhibitor, optimized for inhaled delivery to
improve efficacy and tolerability. The anti-inflammatory activity of CHF 6001 has been
proven in vitro and in several animal models of airway inflammation, showing higher
potency than the marketed oral PDE4 inhibitor (roflumilast) and more targeted
anti-inflammatory effects than corticosteroids in COPD models. The compound is
characterized by a low oral bioavailability, inactive metabolites, high plasma protein
binding, low plasma/lung concentration ratio and low brain exposure. Moreover, CHF 6001
was very well tolerated in extended pre-clinical safety studies and the safety margin
between the anti-inflammatory action and side-effects (such as nausea and emesis) is much
larger in comparison to oral and inhaled PDE4 inhibitors developed to date.
The doses achievable in humans with most PDE4 inhibitors are limited by side effects,
and therefore the optimal therapeutic effects of this class of drug have never been
achieved. The profile of CHF 6001 indicates that it will not be under-dosed in humans to
achieve an acceptable side effect profile, supporting its high potential for the treatment
of COPD and asthma.
About Chiesi Group
Founded in 1935 in Parma (Italy), the Chiesi Group achieved a turnover of 1,056
million Euro in 2011, up by 4.1% on the previous year. The Group, currently has a total of
25 affiliates worldwide and is present in over 60 countries with its drugs, which are
produced at plants in Parma, Blois (France) and Santana de Parnaiba (Brazil). In 2011
investment in R&D reached 169.3 million Euro, equivalent to 16% of the turnover. The R&D
centres in Parma, Paris, Rockville (USA) and Chippenham (UK) integrate their efforts to
work together on the Group’s pre-clinical, clinical and registration programmes. At the
end of 2011, the Chiesi Group’s total staff stood at over 3,800 people, more than 320 of
whom are dedicated to R&D.
The main areas of activity are in respiratory therapeutics and specialist medicine
areas. A clear shift occurred in the last years towards more innovative molecules. The
respiratory pipeline now comprises several classes of novel bronchodilating agents (Long
acting muscarinic antagonists, bifunctional muscarinic antagonists-BETAeta2 Agonits) and
anti-inflammatory agents (PDE4 inhibitors, p38 kinase inhibitors, Neutrophil Elastase
Inhibitors) that provide opportunities for future innovative fixed combinations for the
treatment of asthma and COPD.
SOURCE Chiesi Farmaceutici S.p.A.